National Library of Energy BETA

Sample records for antifungal drug molecules

  1. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Wednesday, 24 February 2010 00:00 Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in

  2. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  3. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  4. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  5. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  6. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  7. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  8. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  9. Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Imaging Antifungal Drug Molecules in Action using Soft X-Ray Tomography Print Humankind has benefitted from a long and productive relationship with yeast. For example, fermentation by yeast is an essential step in the production of bread, beer, wine, and even biofuels. However, not all yeast are beneficial. One strain of yeast, Candida albicans, grows unnoticed on most peoples' skin and in the intestines. In response to certain environmental conditions, C. albicans can switch to a pathogenic

  10. Molecule Nanoweaver Improves Drug Delivery and Treatment Efficacy - Energy

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Innovation Portal Startup America Startup America Industrial Technologies Industrial Technologies Find More Like This Return to Search Molecule Nanoweaver Improves Drug Delivery and Treatment Efficacy Argonne National Laboratory Contact ANL About This Technology <p> Schematic of molecular assembly using molecule nanoweaver. The figure illustrates one of many (general) protocols or processes for creating a film tailored at the nanoscale, but overall having macroscale dimensions. The

  11. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Waukee, IA); Ellanskaya, Irina (Kyiv, UA); Ellanskaya, legal representative, Natalia (Kyiv, UA); Gilliam, Jacob T. (Norwalk, IA); Hunter-Cevera, Jennie (Elliott City, MD); Presnail, James K. (Avondale, PA); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2009-09-15

    The invention relates to antifungal compositions and methods for protecting a plant from a fungal pathogen. Compositions including antifungal polypeptides isolated from a fungal fermentation broth are provided.

  12. Imaging Antifungal Drug Molecules in Action using Soft X-Ray...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    development. Cell CAT Scans: 3-D Cell Imaging Routine medical x rays, such as chest x rays, can be used to identify a number of diseases. But this technique only produces...

  13. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Waukee, IA); Dahlbacka, Glen (Oakland, CA); Elleskaya, Irina (Kyiv, UA); Ellanskaya, legal representative, Natalia (Kyiv, UA); Herrmann, Rafael (Wilmington, DE); Hunter-Cevera, Jennie (Elliott City, MD); McCutchen, Billy F. (College Station, IA); Presnail, James K. (Avondale, PA); Rice, Janet A. (Wilmington, DE); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2011-04-12

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include novel amino acid sequences, and variants and fragments thereof, for antipathogenic polypeptides that were isolated from microbial fermentation broths. Nucleic acid molecules comprising nucleotide sequences that encode the antipathogenic polypeptides of the invention are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention, or variant or fragment thereof, are also disclosed.

  14. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Waukee, IA); Dahlbacka, Glen (Oakland, CA); Ellanskaya, legal representative, Natalia (Kyiv, IL); Herrmann, Rafael (Wilmington, DE); Hunter-Cevera, Jennie (Elliott City, MD); McCutchen, Billy F. (Clive, IA); Presnail, James K. (Avondale, PA); Rice, Janet A. (Wilmington, DE); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA); Ellanskaya, deceased, Irina (Kyiv, IL)

    2007-12-11

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include novel amino acid sequences, and variants and fragments thereof, for antipathogenic polypeptides that were isolated from microbial fermentation broths. Nucleic acid molecules comprising nucleotide sequences that encode the antipathogenic polypeptides of the invention are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention, or variant or fragment thereof, are also disclosed.

  15. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Waukee, IA); Dahlbacka, Glen (Oakland, CA); Elleskaya, Irina (Kyiv, UA); Ellanskaya, legal representative; Natalia (Kyiv, UA); Herrmann, Rafael (Wilmington, DE); Hunter-Cevera, Jennie (Elliott City, MD); McCutchen, Billy F. (College Station, IA); Presnail, James K. (Avondale, PA); Rice, Janet A. (Wilmington, DE); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2010-08-10

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include novel amino acid sequences, and variants and fragments thereof, for antipathogenic polypeptides that were isolated from microbial fermentation broths. Nucleic acid molecules comprising nucleotide sequences that encode the antipathogenic polypeptides of the invention are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention, or variant or fragment thereof, are also disclosed.

  16. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Granger, IA); Dahlbacka, Glen (Oakland, CA); Ellanskaya, Irina (Kyiv, UA); Ellanskaya, legal representative, Natalia (Kyiv, UA); Herrmann, Rafael (Wilmington, DE); Hunter-Cevera, Jennie (Elliott City, MD); McCutchen, Billy F. (College Station, TX); Presnail, James K. (Avondale, PA); Rice, Janet A. (Wilmington, DE); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2012-04-03

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include novel amino acid sequences, and variants and fragments thereof, for antipathogenic polypeptides that were isolated from microbial fermentation broths. Nucleic acid molecules comprising nucleotide sequences that encode the antipathogenic polypeptides of the invention are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention, or variant or fragment thereof, are also disclosed.

  17. NERSC Helps Physicists ID New Molecules With Unique Features

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    applications," they wrote. "These molecules can be used for targeted non-invasive drug delivery. When assembled, the molecules can also form new high strength magnets...

  18. Novel short antibacterial and antifungal peptides with low cytotoxicity:

    Office of Scientific and Technical Information (OSTI)

    Efficacy and action mechanisms (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms Citation Details In-Document Search Title: Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms Research highlights: {yields} Short antimicrobial peptides with nine and eleven residues were developed. {yields} These peptides

  19. X-ray characterization of solid small molecule organic materials

    SciTech Connect (OSTI)

    Billinge, Simon; Shankland, Kenneth; Shankland, Norman; Florence, Alastair

    2014-06-10

    The present invention provides, inter alia, methods of characterizing a small molecule organic material, e.g., a drug or a drug product. This method includes subjecting the solid small molecule organic material to x-ray total scattering analysis at a short wavelength, collecting data generated thereby, and mathematically transforming the data to provide a refined set of data.

  20. Prescription Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Prescription Drugs Prescription Drugs Prescription drug benefits are determined by your medical plan. Contact Prime Therapeutics Prescription drug coverage for retirees Your Blue...

  1. NERSC Helps Physicists ID New Molecules With Unique Features

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NERSC Helps Physicists ID New Molecules With Unique Features NERSC Helps Physicists ID New Molecules With Unique Features Hollow magnetic cage molecules may have applications in technology, healthcare August 10, 2013 NERSC supercomputing resources helped Virginia Commonwealth University (VCU) researchers determine it may be possible to create large, hollow magnetic cage molecules that could be used in medicine as a drug delivery system to noninvasively treat tumors and in other emerging

  2. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and chemistry of small molecules. An international collaboration of researchers from Spain, Scotland, and the U.S. has utilized ALS Beamline 11.3.1 (small-molecule...

  3. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Cool Magnetic Molecules Print Wednesday, 25 May 2011 00:00 Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost

  4. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  5. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  6. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  7. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  8. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  9. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cool Magnetic Molecules Print Certain materials are known to heat up or cool down when they are exposed to a changing magnetic field. This is known as the magnetocaloric effect. All magnetic materials exhibit this effect, but in most cases, it is too small to be technologically useful. Recently, however, the search for special molecules with a surprisingly large capacity to keep cool has heated up, driven by environmental and cost considerations as well as by recent improvements in our ability

  10. Roaming Molecule Dynamics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Roaming Molecule Dynamics - Sandia Energy Energy Search Icon Sandia Home Locations Contact Us Employee Locator Energy & Climate Secure & Sustainable Energy Future Stationary Power Energy Conversion Efficiency Solar Energy Wind Energy Water Power Supercritical CO2 Geothermal Natural Gas Safety, Security & Resilience of the Energy Infrastructure Energy Storage Nuclear Power & Engineering Grid Modernization Battery Testing Nuclear Fuel Cycle Defense Waste Management Programs

  11. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect (OSTI)

    Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

    2009-08-03

    Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.

  12. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same

    DOE Patents [OSTI]

    Croteau, Rodney Bruce (Pullman, WA); Burke, Charles Cullen (Moscow, ID)

    2008-06-24

    In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at 45.degree. C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

  13. Electrochromic Graphene Molecules

    SciTech Connect (OSTI)

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were found to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.

  14. Electrochromic Graphene Molecules

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ji, Zhiqiang; Doorn, Stephen K.; Sykora, Milan

    2015-03-13

    Polyclic aromatic hydrocarbons, also called Graphene Molecules (GMs), with chemical composition C132H36(COOH)2 were synthesized in-situ on the surface of transparent nanocrystaline indium tin oxide (nc-ITO) electrodes. Their electronic structure was studied electrochemically and spectro-electrochemically. Variations in the potential applied onto the nc-ITO/GM electrodes induce only small changes in the observed current but they produce dramatic changes in the absorption of the GMs, which are associated with their oxidation and reduction. Analysis of the absorption changes using modified Nernst equation is used to determine standard potentials associated with the individual charge transfer processes. For the GMs prepared here these were foundmore » to be E1,ox 0 = 0.77± 0.01 V and E2,ox 0 = 1.24 ± 0.02 V vs. NHE for the first and second oxidation and E1,red 0 = -1.50 ± 0.04 V for the first reduction. The charge transfer processes are found to be non-ideal. The non-ideality factors associated with the oxidation and reduction processes suggest presence of strong interactions between the GM redox centers. Under the conditions of potential cycling GMs show rapid (seconds) color change with high contrast and stability. An electrochromic application is demonstrated wherein the GMs are used as the optically active component.« less

  15. Single molecule tracking

    DOE Patents [OSTI]

    Shera, E.B.

    1987-10-07

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photons are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions. 3 figs.

  16. Single molecule tracking

    DOE Patents [OSTI]

    Shera, E. Brooks (Los Alamos, NM)

    1988-01-01

    A detection system is provided for identifying individual particles or molecules having characteristic emission in a flow train of the particles in a flow cell. A position sensitive sensor is located adjacent the flow cell in a position effective to detect the emissions from the particles within the flow cell and to assign spatial and temporal coordinates for the detected emissions. A computer is then enabled to predict spatial and temporal coordinates for the particle in the flow train as a function of a first detected emission. Comparison hardware or software then compares subsequent detected spatial and temporal coordinates with the predicted spatial and temporal coordinates to determine whether subsequently detected emissions originate from a particle in the train of particles. In one embodiment, the particles include fluorescent dyes which are excited to fluoresce a spectrum characteristic of the particular particle. Photones are emitted adjacent at least one microchannel plate sensor to enable spatial and temporal coordinates to be assigned. The effect of comparing detected coordinates with predicted coordinates is to define a moving sample volume which effectively precludes the effects of background emissions.

  17. Aromatic molecules as spintronic devices

    SciTech Connect (OSTI)

    Ojeda, J. H.; Orellana, P. A.; Laroze, D.

    2014-03-14

    In this paper, we study the spin-dependent electron transport through aromatic molecular chains attached to two semi-infinite leads. We model this system taking into account different geometrical configurations which are all characterized by a tight binding Hamiltonian. Based on the Green's function approach with a Landauer formalism, we find spin-dependent transport in short aromatic molecules by applying external magnetic fields. Additionally, we find that the magnetoresistance of aromatic molecules can reach different values, which are dependent on the variations in the applied magnetic field, length of the molecules, and the interactions between the contacts and the aromatic molecule.

  18. Nucleic acids encoding antifungal polypeptides and uses thereof

    DOE Patents [OSTI]

    Altier, Daniel J. (Granger, IA); Ellanskaya, I. A. (Kyiv, UA); Gilliam, Jacob T. (Norwalk, IA); Hunter-Cevera, Jennie (Elliott City, MD); Presnail, James K (Avondale, PA); Schepers, Eric (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2010-11-02

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include an amino acid sequence, and variants and fragments thereof, for an antipathogenic polypeptide that was isolated from a fungal fermentation broth. Nucleic acid molecules that encode the antipathogenic polypeptides of the invention, and antipathogenic domains thereof, are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention are also disclosed.

  19. Quantum transport through aromatic molecules

    SciTech Connect (OSTI)

    Ojeda, J. H.; Rey-González, R. R.; Laroze, D.

    2013-12-07

    In this paper, we study the electronic transport properties through aromatic molecules connected to two semi-infinite leads. The molecules are in different geometrical configurations including arrays. Using a nearest neighbor tight-binding approach, the transport properties are analyzed into a Green's function technique within a real-space renormalization scheme. We calculate the transmission probability and the Current-Voltage characteristics as a function of a molecule-leads coupling parameter. Our results show different transport regimes for these systems, exhibiting metal-semiconductor-insulator transitions and the possibility to employ them in molecular devices.

  20. Drug Retention Times

    SciTech Connect (OSTI)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  1. Drug Retention Times

    SciTech Connect (OSTI)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  2. Antifungal polypeptides

    DOE Patents [OSTI]

    Altier, Daniel J. (Granger, IA); Crane, Virginia C. (Des Moines, IA); Ellanskaya, Irina (Kyiv, UA); Ellanskaya, legal representative, Natalia (Kyiv, UA); Gilliam, Jacob T. (Norwalk, IA); Hunter-Cevera, Jennie (Elliott City, MD); Presnail, James K. (Avondale, PA); Schepers, Eric J. (Port Deposit, MD); Simmons, Carl R. (Des Moines, IA); Torok, Tamas (Richmond, CA); Yalpani, Nasser (Johnston, IA)

    2009-10-06

    The invention relates to compositions including amino acid sequences isolated from fungal fermentation broths and methods for protecting a plant from a pathogen, particularly a fungal pathogen.

  3. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cell. The class of dye molecules used in this research is related to the dye that gives blue jeans their color. By choosing organic molecules, an enormous repertoire of possible...

  4. Ultrafast electron diffraction from aligned molecules

    SciTech Connect (OSTI)

    Centurion, Martin

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  5. Multifunctional hyper-structured molecules

    SciTech Connect (OSTI)

    Wada, T.; Zhang, Y.; Aoyama, T.; Kubo, Y.; Sasabe, H.

    1998-07-01

    To fill the gap between molecular design and the architecture of three-dimensional functional structures, the authors propose novel hyper-structured molecules (HSMs) based on well-defined and topologically controlled molecular systems. To this end they have developed carbazole dendrimers, trimers, cyclic oligomers and chromogenic calix[4]arenes as HSMs. Photorefractivity was selected as the primary target function of these HSMs. Oligomers developed in their laboratory exhibit intrinsic photocarrier generation, transport, electro-optic, film-forming and poling properties. These multifunctional properties allow us to demonstrate optical image processing using optical phase conjugation. The topological shapes of indoaniline-derived calix[4]arenes were studied by hyper-Rayleigh scattering. The two indoaniline moieties in calix[4]arene derivatives were pre-aligned so as to enhance the net molecular hyperpolarizability. Besides dendric oligomers, cyclic oligomers can be used as a molecular platform which allows molecular level tuning of shape, size and topology for superior opto-electronic functions.

  6. Electrokinetic concentration of charged molecules

    DOE Patents [OSTI]

    Singh, Anup K. (Berkeley, CA); Neyer, David W. (Castro Valley, CA); Schoeniger, Joseph S. (Oakland, CA); Garguilo, Michael G. (Livermore, CA)

    2002-01-01

    A method for separating and concentrating charged species from uncharged or neutral species regardless of size differential. The method uses reversible electric field induced retention of charged species, that can include molecules and molecular aggregates such as dimers, polymers, multimers, colloids, micelles, and liposomes, in volumes and on surfaces of porous materials. The retained charged species are subsequently quantitatively removed from the porous material by a pressure driven flow that passes through the retention volume and is independent of direction thus, a multi-directional flow field is not required. Uncharged species pass through the system unimpeded thus effecting a complete separation of charged and uncharged species and making possible concentration factors greater than 1000-fold.

  7. Electrorheological crystallization of proteins and other molecules

    DOE Patents [OSTI]

    Craig, George D. (Lafayette, CA); Rupp, Bernhard (Dublin, CA)

    1996-01-01

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an x-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the x-ray diffraction pattern.

  8. Electrorheological crystallization of proteins and other molecules

    DOE Patents [OSTI]

    Craig, G.D.; Rupp, B.

    1996-06-11

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an X-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the X-ray diffraction pattern. 4 figs.

  9. Non-destructively shattered mesoporous silica for protein drug delivery

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Non-destructively shattered mesoporous silica for protein drug delivery Citation Details In-Document Search Title: Non-destructively shattered mesoporous silica for protein drug delivery Mesoporous silicas have been extensively used for entrapping small chemical molecules and biomacromolecules. We hypothesize that the loading density of biomacromlecules such as proteins in mesoporous silicas could be limited due to mesopore disorderness and depth because

  10. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    single-crystal devices, but rather low-end cells based on organic molecules or conducting polymers. Vital information for making organic solar cells more competitive for widespread...

  11. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    high-efficiency single-crystal devices, but rather low-end cells based on organic molecules or conducting polymers. Vital information for making organic solar cells more...

  12. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell...

  13. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption....

  14. Inverted, semitransparent small molecule photovoltaic cells ...

    Office of Scientific and Technical Information (OSTI)

    small molecule photovoltaic cells Authors: Xiao, Xin 1 ; Lee, Kyusang 1 ; Forrest, Stephen R. 2 + Show Author Affiliations Department of Electrical Engineering and Computer...

  15. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    rows) mix with orbitals of carbon in various configurations has been the subject of debate. Development of more precise models of the electronic structure in molecules with...

  16. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    improvements in organometallic catalysts that are employed across industry for the polymerization of organic molecules. In this study, Minasian et al. quantitatively probe...

  17. Pharmacokinetic drivers of toxicity for basic molecules: Strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor

    SciTech Connect (OSTI)

    Diaz, Dolores; Ford, Kevin A.; Hartley, Dylan P.; Harstad, Eric B.; Cain, Gary R.; Achilles-Poon, Kirsten; Nguyen, Trung; Peng, Jing; Zheng, Zhong; Merchant, Mark; Sutherlin, Daniel P.; Gaudino, John J.; Kaus, Robert; Lewin-Koh, Sock C.; Choo, Edna F.; Liederer, Bianca M.; Dambach, Donna M.

    2013-01-01

    Several toxicities are clearly driven by free drug concentrations in plasma, such as toxicities related to on-target exaggerated pharmacology or off-target pharmacological activity associated with receptors, enzymes or ion channels. However, there are examples in which organ toxicities appear to correlate better with total drug concentrations in the target tissues, rather than with free drug concentrations in plasma. Here we present a case study in which a small molecule Met inhibitor, GEN-203, with significant liver and bone marrow toxicity in preclinical species was modified with the intention of increasing the safety margin. GEN-203 is a lipophilic weak base as demonstrated by its physicochemical and structural properties: high LogD (distribution coefficient) (4.3) and high measured pKa (7.45) due to the basic amine (N-ethyl-3-fluoro-4-aminopiperidine). The physicochemical properties of GEN-203 were hypothesized to drive the high distribution of this compound to tissues as evidenced by a moderately-high volume of distribution (Vd > 3 l/kg) in mouse and subsequent toxicities of the compound. Specifically, the basicity of GEN-203 was decreased through addition of a second fluorine in the 3-position of the aminopiperidine to yield GEN-890 (N-ethyl-3,3-difluoro-4-aminopiperidine), which decreased the volume of distribution of the compound in mouse (Vd = 1.0 l/kg), decreased its tissue drug concentrations and led to decreased toxicity in mice. This strategy suggests that when toxicity is driven by tissue drug concentrations, optimization of the physicochemical parameters that drive tissue distribution can result in decreased drug concentrations in tissues, resulting in lower toxicity and improved safety margins. -- Highlights: ? Lower pKa for a small molecule: reduced tissue drug levels and toxicity. ? New analysis tools to assess electrostatic effects and ionization are presented. ? Chemical and PK drivers of toxicity can be leveraged to improve safety.

  18. Tumor suppressor molecules and methods of use

    DOE Patents [OSTI]

    Welch, Peter J.; Barber, Jack R.

    2004-09-07

    The invention provides substantially pure tumor suppressor nucleic acid molecules and tumor suppressor polypeptides. The invention also provides hairpin ribozymes and antibodies selective for these tumor suppressor molecules. Also provided are methods of detecting a neoplastic cell in a sample using detectable agents specific for the tumor suppressor nucleic acids and polypeptides.

  19. Attachment of second harmonic-active moiety to molecules for detection of molecules at interfaces

    DOE Patents [OSTI]

    Salafsky, Joshua S.; Eisenthal, Kenneth B.

    2005-10-11

    This invention provides methods of detecting molecules at an interface, which comprise labeling the molecules with a second harmonic-active moiety and detecting the labeled molecules at the interface using a surface selective technique. The invention also provides methods for detecting a molecule in a medium and for determining the orientation of a molecular species within a planar surface using a second harmonic-active moiety and a surface selective technique.

  20. Chiral Isotropic Liquids from Achiral Molecules

    SciTech Connect (OSTI)

    L Hough; M Spannuth; M Nakata; D Coleman; C Jones; G Dantlgraber; C Tschierske; J Watanabe; N Clark; et al.

    2011-12-31

    A variety of simple bent-core molecules exhibit smectic liquid crystal phases of planar fluid layers that are spontaneously both polar and chiral in the absence of crystalline order. We found that because of intralayer structural mismatch, such layers are also only marginally stable against spontaneous saddle splay deformation, which is incompatible with long-range order. This results in macroscopically isotropic fluids that possess only short-range orientational and positional order, in which the only macroscopically broken symmetry is chirality - even though the phases are formed from achiral molecules. Their conglomerate domains exhibit optical rotatory powers comparable to the highest ever found for isotropic fluids of chiral molecules.

  1. Denaturing of Molecules | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Do Molecules Get Old? Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to share on LinkedIn (Opens in new window) Click to share on Tumblr (Opens in new window) Do Molecules Get Old? 2012.07.03 Chief Scientist Jim Bray explains how molecules degrade over various time periods, not unlike human aging. 0 Comments Comment Name Email Submit Comment You Might Also Like Vin_Smentlowski_AVS_Registration AVS 61st

  2. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    electron transfer, for example in hemoglobin and cytochrome c. The active center of these dyes-the heme-is similar to that of porphyrin molecules, but it contains additional atoms...

  3. Do triatomic molecules echo atomic periodicity?

    SciTech Connect (OSTI)

    Hefferlin, R. Barrow, J.

    2015-03-30

    Demonstrations of periodicity among triatomic-molecular spectroscopic constants underscore the role of the periodic law as a foundation of chemistry. The objective of this work is to prepare for another test using vibration frequencies ?{sub 1} of free, ground-state, main-group triatomic molecules. Using data from four data bases and from computation, we have collected ?{sub 1} data for molecules formed from second period atoms.

  4. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Biomimetic Dye Molecules for Solar Cells Print Wednesday, 28 April 2010 00:00 Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most

  5. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Covalent Bonding in Actinide Sandwich Molecules Print Wednesday, 28 May 2014 00:00 Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic

  6. Recovery of tritium from tritiated molecules

    DOE Patents [OSTI]

    Swansiger, W.A.

    1984-10-17

    This invention relates to the recovery of tritium from various tritiated molecules by reaction with uranium. More particularly, the invention relates to the recovery of tritium from tritiated molecules by reaction with uranium wherein the reaction is conducted in a reactor which permits the reaction to occur as a moving front reaction from the point where the tritium enters the reactor charged with uranium down the reactor until the uranium is exhausted.

  7. Sol-gel method for encapsulating molecules

    DOE Patents [OSTI]

    Brinker, C. Jeffrey (Albuquerque, NM); Ashley, Carol S. (Albuquerque, NM); Bhatia, Rimple (Albuquerque, NM); Singh, Anup K. (San Francisco, CA)

    2002-01-01

    A method for encapsulating organic molecules, and in particular, biomolecules using sol-gel chemistry. A silica sol is prepared from an aqueous alkali metal silicate solution, such as a mixture of silicon dioxide and sodium or potassium oxide in water. The pH is adjusted to a suitably low value to stabilize the sol by minimizing the rate of siloxane condensation, thereby allowing storage stability of the sol prior to gelation. The organic molecules, generally in solution, is then added with the organic molecules being encapsulated in the sol matrix. After aging, either a thin film can be prepared or a gel can be formed with the encapsulated molecules. Depending upon the acid used, pH, and other processing conditions, the gelation time can be from one minute up to several days. In the method of the present invention, no alcohols are generated as by-products during the sol-gel and encapsulation steps. The organic molecules can be added at any desired pH value, where the pH value is generally chosen to achieve the desired reactivity of the organic molecules. The method of the present invention thereby presents a sufficiently mild encapsulation method to retain a significant portion of the activity of the biomolecules, compared with the activity of the biomolecules in free solution.

  8. Drug Detection Study

    Office of Scientific and Technical Information (OSTI)

    ORISE-07-NSEM-0544 U.S. Department of Energy Office of Health, Safety and Security Office of Security Policy Drug Retention Times Center for Human Reliability Studies Oak Ridge ...

  9. Molecule Nanoweaver Creates High-Tech Medical Patches and Multilayered...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Molecule Nanoweaver Creates High-Tech Medical Patches and Multilayered Capsules Technology available for licensing: Molecule Nanoweaver, a unique tool that can be used as both a...

  10. The spontaneous synchronized dance of pairs of water molecules...

    Office of Scientific and Technical Information (OSTI)

    The spontaneous synchronized dance of pairs of water molecules Citation Details In-Document Search Title: The spontaneous synchronized dance of pairs of water molecules Molecular ...

  11. Protein Scaffolding for Small Molecule Catalysts

    SciTech Connect (OSTI)

    Baker, David

    2014-09-14

    We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

  12. Cavity sideband cooling of trapped molecules

    SciTech Connect (OSTI)

    Kowalewski, Markus; Vivie-Riedle, Regina de [Department of Chemistry, Ludwig-Maximilian-Universitaet, D-81377 Munich (Germany); Morigi, Giovanna [Departament de Fisica, Universitat Autonoma de Barcelona, E-08193 Bellaterra (Spain); Theoretische Physik, Universitaet des Saarlandes, D-66041 Saarbruecken (Germany); Pinkse, Pepijn W. H. [MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500AE Enschede (Netherlands)

    2011-09-15

    The efficiency of cavity sideband cooling of trapped molecules is theoretically investigated for the case in which the infrared transition between two rovibrational states is used as a cycling transition. The molecules are assumed to be trapped either by a radiofrequency or optical trapping potential, depending on whether they are charged or neutral, and confined inside a high-finesse optical resonator that enhances radiative emission into the cavity mode. Using realistic experimental parameters and COS as a representative molecular example, we show that in this setup, cooling to the trap ground state is feasible.

  13. Method for sequencing nucleic acid molecules

    DOE Patents [OSTI]

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2006-06-06

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  14. Method for sequencing nucleic acid molecules

    DOE Patents [OSTI]

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2006-05-30

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  15. Drug development and manufacturing

    DOE Patents [OSTI]

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

    2015-10-13

    X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

  16. Automated imaging system for single molecules

    DOE Patents [OSTI]

    Schwartz, David Charles; Runnheim, Rodney; Forrest, Daniel

    2012-09-18

    There is provided a high throughput automated single molecule image collection and processing system that requires minimal initial user input. The unique features embodied in the present disclosure allow automated collection and initial processing of optical images of single molecules and their assemblies. Correct focus may be automatically maintained while images are collected. Uneven illumination in fluorescence microscopy is accounted for, and an overall robust imaging operation is provided yielding individual images prepared for further processing in external systems. Embodiments described herein are useful in studies of any macromolecules such as DNA, RNA, peptides and proteins. The automated image collection and processing system and method of same may be implemented and deployed over a computer network, and may be ergonomically optimized to facilitate user interaction.

  17. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  18. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  19. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  20. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  1. Allosteric Modulation of DNA by Small Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Allosteric Modulation of DNA by Small Molecules Signals originating at the cell surface are conveyed by a complex system of interconnected signaling pathways to the nucleus. They converge at transcription factors, which in turn regulate the transcription of sets of genes that result in the gene expression. Many human diseases are caused by dysregulated gene expression and the oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell

  2. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  3. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  4. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  5. Biomimetic Dye Molecules for Solar Cells

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomimetic Dye Molecules for Solar Cells Print Pressing energy problems provide opportunities for solid-state physicists and chemists to solve a major challenge: solar cell adoption. Though solar cells can use energy directly from the Sun to produce electricity that can be converted efficiently into other kinds of energy, they are currently too costly to compete with traditional (polluting) energy sources. The most cost-effective solar cells are not high-end, high-efficiency single-crystal

  6. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  7. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  8. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  9. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  10. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  11. Covalent Bonding in Actinide Sandwich Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Covalent Bonding in Actinide Sandwich Molecules Print Glenn Seaborg was one of the first scientists to recognize that differences in the degree of covalent bonding in lanthanide and actinide compounds could have profound consequences for their unique chemical reactivity and physical properties. Now, researchers working at ALS Beamline 11.0.2 have found evidence for unexpected bonding interactions in two organometallic actinide "sandwich" complexes that have been lightning rods in

  12. Copper(II) complexes with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid: Syntheses, crystal structures and antifungal activities

    SciTech Connect (OSTI)

    Xiong, Pingping; Li, Jie; Bu, Huaiyu; Wei, Qing; Zhang, Ruolin; Chen, Sanping

    2014-07-01

    Reaction of Cu(II) with an asymmetric semi-rigid organic ligand 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid (HL), yielded five compounds, [Cu{sub 0.5}L]{sub n} (1), [Cu(HL){sub 2}Cl{sub 2}]{sub n} (2), [Cu(HL){sub 2}Cl{sub 2}(H{sub 2}O)] (3), [Cu(L){sub 2}(H{sub 2}O)]{sub n} (4) and [Cu(L)(phen)(HCO{sub 2})]{sub n} (5), which have been fully characterized by infrared spectroscopy, elemental analysis, and single-crystal X-ray diffraction. As for compounds 1, 2 and 5, Cu(II) is bridged through HL, Cl{sup -}, and formic acid, respectively, featuring 1D chain-structure. In compound 3, Cu(II) with hexahedral coordination sphere is assembled through hydrogen-bonding into 3D supramolecular framework. In compound 4, 1D chain units –Cu–O–Cu–O– are ligand-bridged into a 3D network. All compounds were tested on fungi (Fusarium graminearum, Altemaria solani, Macrophoma kawatsukai, Alternaria alternata and Colletotrichum gloeosporioides). Compound 1 exhibits a better antifungal effect compared to other compounds. An effect of structure on the antifungal activity has also been correlated. - Graphical abstract: Copper(II) compounds with 4-(1H-1, 2, 4-trizol-1-ylmethyl) benzoic acid, were prepared, structurally characterized and investigated for antifungal activity. - Highlights: • The title compounds formed by thermodynamics and thermokinetics. • The five compounds show higher inhibition percentage than reactants. • The structure effect on the antifungal activity.

  13. Identification of cell density signal molecule

    DOE Patents [OSTI]

    Schwarz, Richard I. (Oakland, CA)

    1998-01-01

    Disclosed herein is a novel proteinaceous cell density signal molecule (CDS) between 25 and 35 kD, which is secreted by fibroblastic primary avian tendon cells in culture, and causes the cells to self-regulate their proliferation and the expression of differentiated function. It effects an increase of procollagen production in avian tendon cell cultures of ten fold while proliferation rates are decreased. CDS, and the antibodies which recognize them, are important for the development of diagnostics and treatments for injuries and diseases involving connective tissues, particularly tendon. Also disclosed are methods of production and use.

  14. Identification of cell density signal molecule

    DOE Patents [OSTI]

    Schwarz, R.I.

    1998-04-21

    Disclosed herein is a novel proteinaceous cell density signal molecule (CDS) between 25 and 35 kD, which is secreted by fibroblastic primary avian tendon cells in culture, and causes the cells to self-regulate their proliferation and the expression of differentiated function. It effects an increase of procollagen production in avian tendon cell cultures of ten fold while proliferation rates are decreased. CDS, and the antibodies which recognize them, are important for the development of diagnostics and treatments for injuries and diseases involving connective tissues, particularly tendon. Also disclosed are methods of production and use. 2 figs.

  15. Nanodevices for generating power from molecules and batteryless sensing

    DOE Patents [OSTI]

    Wang, Yinmin; Wang, Xianying; Hamza, Alex V.

    2014-07-15

    A nanoconverter or nanosensor is disclosed capable of directly generating electricity through physisorption interactions with molecules that are dipole containing organic species in a molecule interaction zone. High surface-to-volume ratio semiconductor nanowires or nanotubes (such as ZnO, silicon, carbon, etc.) are grown either aligned or randomly-aligned on a substrate. Epoxy or other nonconductive polymers are used to seal portions of the nanowires or nanotubes to create molecule noninteraction zones. By correlating certain molecule species to voltages generated, a nanosensor may quickly identify which species is detected. Nanoconverters in a series parallel arrangement may be constructed in planar, stacked, or rolled arrays to supply power to nano- and micro-devices without use of external batteries. In some cases breath, from human or other life forms, contain sufficient molecules to power a nanoconverter. A membrane permeable to certain molecules around the molecule interaction zone increases specific molecule nanosensor selectivity response.

  16. Models from Big Molecules Captured in a Flash

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Models from Big Molecules Captured in a Flash Models from Big Molecules Captured in a Flash Print Sunday, 26 May 2013 00:00 The structures of most of the two million proteins in...

  17. Nanodevices for generating power from molecules and batteryless sensing

    DOE Patents [OSTI]

    Wang, Yinmin; Wang, Xianying; Hamza, Alex V.

    2015-06-09

    A nanoconverter or nanosensor is disclosed capable of directly generating electricity through physisorption interactions with molecules that are dipole containing organic species in a molecule interaction zone. High surface-to-volume ratio semiconductor nanowires or nanotubes (such as ZnO, silicon, carbon, etc.) are grown either aligned or randomly-aligned on a substrate. Epoxy or other nonconductive polymers are used to seal portions of the nanowires or nanotubes to create molecule noninteraction zones. By correlating certain molecule species to voltages generated, a nanosensor may quickly identify which species is detected. Nanoconverters in a series parallel arrangement may be constructed in planar, stacked, or rolled arrays to supply power to nano- and micro-devices without use of external batteries. In some cases breath, from human or other life forms, contain sufficient molecules to power a nanoconverter. A membrane permeable to certain molecules around the molecule interaction zone increases specific molecule nanosensor selectivity response.

  18. Toroidal nanotraps for cold polar molecules

    SciTech Connect (OSTI)

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-14

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, and polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.

  19. Toroidal nanotraps for cold polar molecules

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-14

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, andmore » polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.« less

  20. Time-Resolved SAXS/WAXS Study of the Phase Behavior and Microstructural Evolution of Drug/PEG Solid Dispersions

    SciTech Connect (OSTI)

    Zhu, Qing; Harris, Michael T.; Taylor, Lynne S.

    2013-03-07

    Simultaneous small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS) was employed to elucidate the physical state and location of various small molecule drugs blended with polyethylene glycol (PEG), as well as the time dependent microstructural evolution of the systems. Samples were prepared by comelting physical mixtures of the drug and PEG, followed by solidification at 25 C. The model drugs selected encompassed a wide variety of physicochemical properties in terms of crystallization tendency and potential for interaction with PEG. It was observed that compounds which crystallized rapidly and had weak interactions with PEG tended to be excluded from the interlamellar region of the PEG matrix. In contrast, drugs which had favorable interactions with PEG were incorporated into the interlamellar regions of the polymer up until the point at which the drug crystallized whereby phase separation occurred. These factors are likely to impact the effectiveness of drug/PEG systems as drug delivery systems.

  1. Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

    SciTech Connect (OSTI)

    Saha, Dipendu; Warren, Kaitlyn E; Naskar, Amit K

    2014-01-01

    Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1. The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.

  2. Microfabricated injectable drug delivery system

    DOE Patents [OSTI]

    Krulevitch, Peter A. (Pleasanton, CA); Wang, Amy W. (Oakland, CA)

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  3. Glucose sensing molecules having selected fluorescent properties

    DOE Patents [OSTI]

    Satcher, Jr., Joe H.; Lane, Stephen M.; Darrow, Christopher B.; Cary, Douglas R.; Tran, Joe Anh

    2004-01-27

    An analyte sensing fluorescent molecule that employs intramolecular electron transfer is designed to exhibit selected fluorescent properties in the presence of analytes such as saccharides. The selected fluorescent properties include excitation wavelength, emission wavelength, fluorescence lifetime, quantum yield, photostability, solubility, and temperature or pH sensitivity. The compound comprises an aryl or a substituted phenyl boronic acid that acts as a substrate recognition component, a fluorescence switch component, and a fluorophore. The fluorophore and switch component are selected such that the value of the free energy for electron transfer is less than about 3.0 kcal mol.sup.-1. Fluorescent compounds are described that are excited at wavelengths greater than 400 nm and emit at wavelengths greater than 450 nm, which is advantageous for optical transmission through skin. The fluorophore is typically selected from transition metal-ligand complexes and thiazine, oxazine, oxazone, or oxazine-one as well as anthracene compounds. The fluorescent compound can be immobilized in a glucose permeable biocompatible polymer matrix that is implantable below the skin.

  4. Orientational Analysis of Molecules in Thin Films | Stanford Synchrotron

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Radiation Lightsource Orientational Analysis of Molecules in Thin Films Monday, September 17, 2012 - 10:00am SSRL Bldg. 137, room 226 Daniel Kaefer The synchrotron-based X-ray absorption spectroscopy is a very powerful tool to unravel the orientation of organic molecules on surfaces or in thin films. This information on the alignment of - most often - highly anisotropic molecules can become crucial if an epitaxial or even crystalline organic growth is desired, if such thin film should serve

  5. Target molecules detection by waveguiding in a photonic silicon membrane

    DOE Patents [OSTI]

    Letant, Sonia E. (Livermore, CA); Van Buuren, Anthony (Livermore, CA); Terminello, Louis (Danville, CA); Hart, Bradley R. (Brentwood, CA)

    2006-12-26

    Disclosed herein is a porous silicon filter capable of binding and detecting biological and chemical target molecules in liquid or gas samples. A photonic waveguiding silicon filter with chemical and/or biological anchors covalently attached to the pore walls bind target molecules. The system uses transmission curve engineering principles to allow measurements to be made in situ and in real time to detect the presence of various target molecules and calculate the concentration of bound target.

  6. Drug Testing Notification | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Drug Testing Notification Drug Testing Notification PDF icon Drug Testing Notification More Documents & Publications Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC Fact Sheet on the Consequences of a Positive Drug Test PSH-13-0022 - In the Matter of Personnel Security

  7. Mapping protein collapse with single molecule fluorescence and...

    Office of Scientific and Technical Information (OSTI)

    single molecule fluorescence and kinetic synchrotron radiation circular dichroism spectroscopy Citation Details In-Document Search Title: Mapping protein collapse with single...

  8. Systematic expansion of porous crystals to include large molecules | Center

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Systematic expansion of porous crystals to include large molecules

  9. Molecule@MOF: A New Class of Electronic Materials

    Office of Scientific and Technical Information (OSTI)

    22PE Exceptional service in the national interest Sandia National Laboratories Molecule@MOF: A New Class of Electronic Materials A. Alec Talin Sandia National Labs, Livermore, CA ...

  10. Making Maps of the Molecules in Seeds | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Making Maps of the Molecules in Seeds Scientists have advanced methods to make maps of the locations of molecules within plant materials. Resolution of 10 to 50 microns, less than a quarter the size of a human hair, is routinely possible. The trick with plant materials is to extract the molecules delicately from thin slices with a fine laser moving stepwise across the sample.Many molecules are analyzed at once using a very sensitive mass spectrometer in this technique known as matrix-assisted

  11. Researchers use light to create rare uranium molecule

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    The uranium nitride molecule derived from the photolysis process is well defined, unlike solid-state compounds from alternative processes, making it ideal for the controlled study...

  12. Self-contained Kondo effect in single molecules (Journal Article...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Self-contained Kondo effect in single molecules Citation Details ... OSTI Identifier: 877620 Report Number(s): LBNL--57492 Journal ID: ISSN 0031-9007; PRLTAO; ...

  13. Micro injector sample delivery system for charged molecules

    DOE Patents [OSTI]

    Davidson, James C. (Livermore, CA); Balch, Joseph W. (Livermore, CA)

    1999-11-09

    A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

  14. The statistics of single molecule detection: An overview

    SciTech Connect (OSTI)

    Enderlein, J.; Robbins, D.L.; Ambrose, W.P.

    1995-12-31

    An overview of our recent results in modeling single molecule detection in fluid flow is presented. Our mathematical approach is based on a path integral representation. The model accounts for all experimental details, such as light collection, laser excitation, hydrodynamics and diffusion, and molecular photophysics. Special attention is paid to multiple molecule crossings through the detection volume. Numerical realization of the theory is discussed. Measurements of burst size distributions in single B-phycoerythrin molecule detection experiments are presented and compared with theoretical predictions.

  15. Recent progress in electron scattering from atoms and molecules

    SciTech Connect (OSTI)

    Brunger, M. J.; Buckman, S. J.; Sullivan, J. P.; Palihawadana, P.; Jones, D. B.; Chiari, L.; Pettifer, Z.; Silva, G. B. da; Lopes, M. C. A.; Duque, H. V.; Masin, Z.; Gorfinkiel, J. D.; Garcia, G.; Hoshino, M.; Tanaka, H.; Limão-Vieira, P.

    2014-03-05

    We present and discuss recent results, both experimental and theoretical (where possible), for electron impact excitation of the 3s[3/2 ]{sub 1} and 3s?[1/2 ]{sub 1} electronic states in neon, elastic electron scattering from the structurally similar molecules benzene, pyrazine, and 1,4-dioxane and excitation of the electronic states of the important bio-molecule analogue ?-tetrahydrofurfuryl alcohol. While comparison between theoretical and experimental results suggests that benchmarked cross sections for electron scattering from atoms is feasible in the near-term, significant further theoretical development for electron-molecule collisions, particularly in respect to discrete excitation processes, is still required.

  16. Models from Big Molecules Captured in a Flash

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Models from Big Molecules Captured in a Flash Models from Big Molecules Captured in a Flash Print Sunday, 26 May 2013 00:00 The structures of most of the two million proteins in the human body are unknown because they can't be crystallized. Peter Zwart of the Physical Biosciences Division and his colleagues have come up with a new algorithm for efficiently solving the structures of proteins and other big molecules in their more natural fluid states, using the "diffract before destroy"

  17. Isolated menthone reductase and nucleic acid molecules encoding same

    DOE Patents [OSTI]

    Croteau, Rodney B; Davis, Edward M; Ringer, Kerry L

    2013-04-23

    The present invention provides isolated menthone reductase proteins, isolated nucleic acid molecules encoding menthone reductase proteins, methods for expressing and isolating menthone reductase proteins, and transgenic plants expressing elevated levels of menthone reductase protein.

  18. Understanding Small Molecule Interactions in Metal-Organic Frameworks:

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Coupling Experiment with Theory | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Understanding Small Molecule Interactions in Metal-Organic Frameworks: Coupling Experiment with Theory

  19. Atom-diatom scattering dynamics of spinning molecules

    SciTech Connect (OSTI)

    Eyles, C. J.; Floß, J.; Averbukh, I. Sh.; Leibscher, M.

    2015-01-14

    We present full quantum mechanical scattering calculations using spinning molecules as target states for nuclear spin selective atom-diatom scattering of reactive D+H{sub 2} and F+H{sub 2} collisions. Molecules can be forced to rotate uni-directionally by chiral trains of short, non-resonant laser pulses, with different nuclear spin isomers rotating in opposite directions. The calculations we present are based on rotational wavepackets that can be created in this manner. As our simulations show, target molecules with opposite sense of rotation are predominantly scattered in opposite directions, opening routes for spatially and quantum state selective scattering of close chemical species. Moreover, two-dimensional state resolved differential cross sections reveal detailed information about the scattering mechanisms, which can be explained to a large degree by a classical vector model for scattering with spinning molecules.

  20. Stable Metal-Organic Frameworks Containing Single-Molecule Traps...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stable Metal-Organic Frameworks Containing Single-Molecule Traps for Enzyme Encapsulation Previous Next List Dawei Feng, Tian-Fu Liu, Jie Su, Mathieu Bosch, Zhangwen Wei, Wei Wan,...

  1. Capture and Release of Guest Molecules by Optical Responsive

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Metal-Organic Polyhedra (MOP) | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Capture and Release of Guest Molecules by Optical Responsive Metal-Organic Polyhedra (MOP)

  2. Frontiers in Laser Cooling, Single-Molecule Biophysics, and Enrgy...

    Office of Scientific and Technical Information (OSTI)

    Frontiers in Laser Cooling, Single-Molecule Biophysics, and Enrgy Science: A Talk from Paul Alivisatos titled LBNL in the Chu Era Citation Details In-Document Search Title:...

  3. Orientational Analysis of Molecules in Thin Films | Stanford...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Molecules in Thin Films Monday, September 17, 2012 - 10:00am SSRL Bldg. 137, room 226 Daniel Kaefer The synchrotron-based X-ray absorption spectroscopy is a very powerful tool to...

  4. Nanopost Arrays Anchor Molecules, Improve Ion Yields for Laser...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    in a broad range of geometries are being developed at ORNL. These can be used as matrices to detect and analyze molecules by laser mass spectrometry: A matrix of nanoposts...

  5. Method of monitoring photoactive organic molecules in-situ during gas-phase deposition of the photoactive organic molecules

    SciTech Connect (OSTI)

    Forrest, Stephen R.; Vartanian, Garen; Rolin, Cedric

    2015-06-23

    A method for in-situ monitoring of gas-phase photoactive organic molecules in real time while depositing a film of the photoactive organic molecules on a substrate in a processing chamber for depositing the film includes irradiating the gas-phase photoactive organic molecules in the processing chamber with a radiation from a radiation source in-situ while depositing the film of the one or more organic materials and measuring the intensity of the resulting photoluminescence emission from the organic material. One or more processing parameters associated with the deposition process can be determined from the photoluminescence intensity data in real time providing useful feedback on the deposition process.

  6. Nitrogen molecule activation by excited states of copper

    SciTech Connect (OSTI)

    Sanchez-Zamora, M.; Novaro, O.; Ruiz, M.E. )

    1990-04-05

    Ab initio molecular orbital studies that include variational (with a multiconfiguration reference state of 200 states) and perturbational (including over 3 million configurations) configuration interaction calculations were addressed to the interaction of nitrogen molecules with copper. The Cu ground state {sup 2}S and first two excited states {sup 2}P and {sup 2}D were studied as they interact in different geometrical approaches (including side-on and end-on geometries) with ground-state N{sub 2} molecules.

  7. Guest Molecule Induced Switching of Electrical Conduction in a

    Office of Scientific and Technical Information (OSTI)

    Metal-Organic Framework. (Journal Article) | SciTech Connect Guest Molecule Induced Switching of Electrical Conduction in a Metal-Organic Framework. Citation Details In-Document Search Title: Guest Molecule Induced Switching of Electrical Conduction in a Metal-Organic Framework. Authors: Stavila, Vitalie ; Talin, Albert Alec ; Allendorf, Mark D. ; Foster, Michael E. ; Centrone, Andrea ; Haney, Paul ; Kinney, R. Adam ; Szalai, Veronika ; Yook, Heayoung ; Thurston, Bryce ; Buzmetov, Dmitry

  8. Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer

    Office of Scientific and Technical Information (OSTI)

    Mechanochemistry (Journal Article) | SciTech Connect Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer Mechanochemistry Citation Details In-Document Search Title: Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer Mechanochemistry Authors: Wang, J ; Kouznetsova, T B ; Niu, Z ; Ong, M T ; Klukovich, H M ; Rheingold, A L ; Martinez, T J ; Craig, S L Publication Date: 2014-11-05 OSTI Identifier: 1184168 Report Number(s): LLNL-JRNL-663754 DOE

  9. Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer

    Office of Scientific and Technical Information (OSTI)

    Mechanochemistry (Journal Article) | SciTech Connect Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer Mechanochemistry Citation Details In-Document Search Title: Inducing and Quantifying Forbidden Reactivity with Single Molecule Polymer Mechanochemistry × You are accessing a document from the Department of Energy's (DOE) SciTech Connect. This site is a product of DOE's Office of Scientific and Technical Information (OSTI) and is provided as a public service. Visit

  10. Mechanistic characterization and crystal structure of a small molecule

    Office of Scientific and Technical Information (OSTI)

    inactivator bound to plasminogen activator inhibitor-1 (Journal Article) | SciTech Connect Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1 Citation Details In-Document Search Title: Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1 Authors: Li, Shih-Hon ; Reinke, Ashley A. ; Sanders, Karen L. ; Emal, Cory D. ; Whisstock, James C. ; Stuckey,

  11. Extracting vibrational beat signatures in spectrally dense molecules using

    Office of Scientific and Technical Information (OSTI)

    multi-pulse femtosecond coherent anti-Stokes Raman spectroscopy. (Journal Article) | SciTech Connect Extracting vibrational beat signatures in spectrally dense molecules using multi-pulse femtosecond coherent anti-Stokes Raman spectroscopy. Citation Details In-Document Search Title: Extracting vibrational beat signatures in spectrally dense molecules using multi-pulse femtosecond coherent anti-Stokes Raman spectroscopy. No abstract prepared. Authors: Nelson, Thomas Robert ; Urayama, Junji

  12. A Suite of Engineered GFP Molecules for Oligomeric Scaffolding (Journal

    Office of Scientific and Technical Information (OSTI)

    Article) | SciTech Connect A Suite of Engineered GFP Molecules for Oligomeric Scaffolding Citation Details In-Document Search Title: A Suite of Engineered GFP Molecules for Oligomeric Scaffolding Authors: Leibly, David J. ; Arbing, Mark A. ; Pashkov, Inna ; DeVore, Natasha ; Waldo, Geoffrey S. ; Terwilliger, Thomas C. ; Yeates, Todd O. [1] ; LANL) [2] + Show Author Affiliations UCLA ( Publication Date: 2015-11-30 OSTI Identifier: 1227481 Resource Type: Journal Article Resource Relation:

  13. Conference: Frontiers in Laser Cooling, Single-Molecule Biophysics, and

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Energy Science: Remarks from Steve Chu at the Scientific Symposium Held in his Honor | ScienceCinema Frontiers in Laser Cooling, Single-Molecule Biophysics, and Energy Science: Remarks from Steve Chu at the Scientific Symposium Held in his Honor Citation Details Title: Frontiers in Laser Cooling, Single-Molecule Biophysics, and Energy Science: Remarks from Steve Chu at the Scientific Symposium Held in his Honor

  14. Efficient Monte Carlo Simulations of Gas Molecules Inside Porous Materials

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Efficient Monte Carlo Simulations of Gas Molecules Inside Porous Materials Previous Next List J. Kim and B. Smit, J. Chem. Theory Comput. 8 (7), 2336 (2012) DOI: 10.1021/ct3003699 Abstract: Monte Carlo (MC) simulations are commonly used to obtain adsorption properties of gas molecules inside porous materials. In this work, we discuss various optimization strategies that lead to faster MC simulations with CO2

  15. Los Alamos scientists detect and track single molecules with nanoscale

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    carbon cylinders Nanotube "glowsticks" transform surface science tool kit Los Alamos scientists detect and track single molecules with nanoscale carbon cylinders Researchers have now shown that semiconducting carbon nanotubes have the potential to detect and track single molecules in water. January 10, 2012 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering

  16. Understanding Small-Molecule Interactions in Metal-Organic Frameworks:

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Coupling Experiment with Theory | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Understanding Small-Molecule Interactions in Metal-Organic Frameworks: Coupling Experiment with Theory Previous Next List Lee, Jason S.; Vlaisavljevich, Bess; Britt, David K.; Brown, Craig M.; Haranczyk, Maciej; Neaton, Jeffrey B.; Smit, Berend; Long, Jeffrey R.; and Queen, Wendy L.. Understanding Small-Molecule Interactions in Metal-Organic Frameworks: Coupling Experiment with

  17. Molecule Nanoweaver Creates High-Tech Medical Patches and Multilayered

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Capsules | Argonne National Laboratory Molecule Nanoweaver Creates High-Tech Medical Patches and Multilayered Capsules Technology available for licensing: Molecule Nanoweaver, a unique tool that can be used as both a detector and a fabricator of high-tech patches, multilayered capsules, and other medical products. May increase the market for medical patches Allows creation of medical patches that are more efficient at delivering medication and treatment, speeding up the healing process PDF

  18. Methods And Devices For Characterizing Duplex Nucleic Acid Molecules

    DOE Patents [OSTI]

    Akeson, Mark (Santa Cruz, CA); Vercoutere, Wenonah (Santa Cruz, CA); Haussler, David (Santa Cruz, CA); Winters-Hilt, Stephen (Santa Cruz, CA)

    2005-08-30

    Methods and devices are provided for characterizing a duplex nucleic acid, e.g., a duplex DNA molecule. In the subject methods, a fluid conducting medium that includes a duplex nucleic acid molecule is contacted with a nanopore under the influence of an applied electric field and the resulting changes in current through the nanopore caused by the duplex nucleic acid molecule are monitored. The observed changes in current through the nanopore are then employed as a set of data values to characterize the duplex nucleic acid, where the set of data values may be employed in raw form or manipulated, e.g., into a current blockade profile. Also provided are nanopore devices for practicing the subject methods, where the subject nanopore devices are characterized by the presence of an algorithm which directs a processing means to employ monitored changes in current through a nanopore to characterize a duplex nucleic acid molecule responsible for the current changes. The subject methods and devices find use in a variety of applications, including, among other applications, the identification of an analyte duplex DNA molecule in a sample, the specific base sequence at a single nulceotide polymorphism (SNP), and the sequencing of duplex DNA molecules.

  19. Single molecule detection using charge-coupled device array technology

    SciTech Connect (OSTI)

    Denton, M.B.

    1992-07-29

    A technique for the detection of single fluorescent chromophores in a flowing stream is under development. This capability is an integral facet of a rapid DNA sequencing scheme currently being developed by Los Alamos National Laboratory. In previous investigations, the detection sensitivity was limited by the background Raman emission from the water solvent. A detection scheme based on a novel mode of operating a Charge-Coupled Device (CCD) is being developed which should greatly enhance the discrimination between fluorescence from a single molecule and the background Raman scattering from the solvent. Register shifts between rows in the CCD are synchronized with the sample flow velocity so that fluorescence from a single molecule is collected in a single moving charge packet occupying an area approaching that of a single pixel while the background is spread evenly among a large number of pixels. Feasibility calculations indicate that single molecule detection should be achieved with an excellent signal-to-noise ratio.

  20. A general strategy to construct small molecule biosensors in eukaryotes

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Feng, Justin; Jester, Benjamin W.; Tinberg, Christine E.; Mandell, Daniel J.; Antunes, Mauricio S.; Chari, Raj; Morey, Kevin J.; Rios, Xavier; Medford, June I.; Church, George M.; et al

    2015-12-29

    Biosensors for small molecules can be used in applications that range from metabolic engineering to orthogonal control of transcription. Here, we produce biosensors based on a ligand-binding domain (LBD) by using a method that, in principle, can be applied to any target molecule. The LBD is fused to either a fluorescent protein or a transcriptional activator and is destabilized by mutation such that the fusion accumulates only in cells containing the target ligand. We illustrate the power of this method by developing biosensors for digoxin and progesterone. Addition of ligand to yeast, mammalian, or plant cells expressing a biosensor activatesmore » transcription with a dynamic range of up to ~100-fold. We use the biosensors to improve the biotransformation of pregnenolone to progesterone in yeast and to regulate CRISPR activity in mammalian cells. This work provides a general methodology to develop biosensors for a broad range of molecules in eukaryotes.« less

  1. Drug Testing for DOE Positions | Department of Energy

    Energy Savers [EERE]

    Drug Testing for DOE Positions Drug Testing for DOE Positions Drug Testing for DOE Positions Drug Testing Matrix Secretary Bodman's Memorandum Regarding Drug Testing at DOE Fact Sheet on the Consequences of a Positive Drug Test View Frequently Asked Questions Ask a Question - Please submit questions related only to drug testing for DOE positions. Contact Dawn Cheek

  2. Spectroscopic and dynamical studies of highly energized small polyatomic molecules

    SciTech Connect (OSTI)

    Field, R.W.; Silbey, R.J.

    1990-01-01

    The formyl radical and the acetylene molecule were chosen for these studies. The visible and fluorescence spectra of the formyl radical were recorded, and the spectral results are used as a basis to explain the electronic structure. Optical-optical double resonance studies of acetylene were recorded, and the spectral results are interpreted. The results of Zeeman and Stark anticrossing and quantum beat studies of acetylene are reported, and they provide an unusually detailed view of both Intersystem Crossing and Internal Conversion in small polyatomic molecules. 22 references are cited as resulting from Department of Energy sponsorship of this project.

  3. Diatomic molecules in optical and microwave dipole traps

    SciTech Connect (OSTI)

    Lysebo, Marius; Veseth, Leif

    2011-03-15

    The dipole forces on rotating diatomic molecules are worked out in detail for optical as well as microwave radiation fields. The objective is in particular to investigate how the dipole forces and potentials depend on the subtle internal structure of the molecule, with special emphasis on hyperfine and Zeeman states. Dipole potentials are obtained from computations of the real part of the complex molecular polarizability, whereas the imaginary part yields the scattering force. Numerical examples are presented for {sup 23}Na{sub 2} and OH for optical (laser) fields related to strong electronic transitions and for microwave fields for the {Lambda} doubling in the OH ground state.

  4. Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC Intergrated Drug Testing System, PIA, Bechtel ...

  5. Single Molecule Study of Cellulase Hydrolysis of Crystalline Cellulose

    SciTech Connect (OSTI)

    Liu, Y.-S.; Luo, Y.; Baker, J. O.; Zeng, Y.; Himmel, M. E.; Smith, S.; Ding, S.-Y.

    2009-12-01

    This report seeks to elucidate the role of cellobiohydrolase-I (CBH I) in the hydrolysis of crystalline cellulose. A single-molecule approach uses various imaging techniques to investigate the surface structure of crystalline cellulose and changes made in the structure by CBH I.

  6. Small-Molecule Inhibition of TNF-alpha

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Farrington, G., Eldredge, J.K., Day, E.S., Cruz, L.A., Cachero, T.G., Miller, S.K., Friedman, J.E., Choong, I.C., Cunningham, B.C. Small-molecule inhibition of TNF-alpha. Science...

  7. Translation and integration of numerical atomic orbitals in linear molecules

    SciTech Connect (OSTI)

    Heinäsmäki, Sami

    2014-02-14

    We present algorithms for translation and integration of atomic orbitals for LCAO calculations in linear molecules. The method applies to arbitrary radial functions given on a numerical mesh. The algorithms are based on pseudospectral differentiation matrices in two dimensions and the corresponding two-dimensional Gaussian quadratures. As a result, multicenter overlap and Coulomb integrals can be evaluated effectively.

  8. Analyte sensing mediated by adapter/carrier molecules

    DOE Patents [OSTI]

    Bayley, Hagan (College Station, TX); Braha, Orit (College Station, TX); Gu, LiQun (Bryan, TX)

    2002-07-30

    This invention relates to an improved method and system for sensing of one or more analytes. A host molecule, which serves as an adapter/carrier, is used to facilitate interaction between the analyte and the sensor element. A detectable signal is produced reflecting the identity and concentration of analyte present.

  9. Spontaneous Liver Rupture After Treatment With Drug-Eluting Beads...

    Office of Scientific and Technical Information (OSTI)

    ANTIBIOTICS; ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC DRUGS; BODY; CARCINOMAS; DIGESTIVE SYSTEM; DISEASES; DRUGS; FAILURES; GLANDS; NEOPLASMS; ORGANIC COMPOUNDS; ORGANS; ...

  10. Apparatus and method of determining molecular weight of large molecules

    DOE Patents [OSTI]

    Fuerstenau, Stephen (Montrose, CA); Benner, W. Henry (Danville, CA); Madden, Norman (Livermore, CA); Searles, William (Fremont, CA)

    1998-01-01

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e.sup.- are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.

  11. Apparatus and method of determining molecular weight of large molecules

    DOE Patents [OSTI]

    Fuerstenau, S.; Benner, W.H.; Madden, N.M.; Searles, W.

    1998-06-23

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e{sup {minus}} are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation. 14 figs.

  12. Neuroimaging for drug addiction and related behaviors

    SciTech Connect (OSTI)

    Parvaz M. A.; Parvaz, M.A.; Alia-Klein, N.; Woicik,P.A.; Volkow, N.D.; Goldstein, R.Z.

    2011-10-01

    In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors.

  13. Ro-vibrational Relaxation Dynamics of PbF Molecules

    SciTech Connect (OSTI)

    Neil Shafer-Ray

    2011-04-08

    In 1950 Purcell and Ramsey suggested that the electron might have a CP-violating electric dipole moment (e-EDM) proportional to its spin angular momentum. This possibility initiated an ongoing hunt for the e-EDM that has been spurred on by the recognition of the importance of CP-violation to the formation of a matter-dominated universe[2] as well as a difference in magnitude of the Supersymmetric and Standard Model[4] prediction for its value. The current limit on the e-EDM is 1.6Eâ??27 e·cm as determined in a Ramsey beam resonance study of the Tl atom. The PbF molecule provides a unique opportunity to measure the e-EDM. The moleculeâ??s odd electron, heavy mass, and large internal field combine to give it an intrinsic sensitivity to an e-EDM that is over three orders of magnitude bigger than that of the Tl atom. In addition to this increased intrinsic sensitivity, the ground state of the PbF molecule allows for a "magic" electric field at which the magnetic moment vanishes[7]. All of these advantages create an opportunity to significantly lower the current limit on the e-EDM. These advantages can only be realized if an intense source of ground-state PbF molecules can be created and detected with high efficiency. The scope of this project is to (1) create a rotationally cold molecular beam source of PbF, (2) achieve a continuous ionization scheme for sensitive state selective detection of the PbF molecule.

  14. Anatomic and Functional Imaging of Tagged Molecules in Animals - Energy

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Innovation Portal Anatomic and Functional Imaging of Tagged Molecules in Animals Thomas Jefferson National Accelerator Facility Contact TJNAF About This Technology Technology Marketing SummaryA novel functional imaging system for use in the imaging of unrestrained and non-anesthetized small animals or other subjects and a method for acquiring such images and further registering them with anatomical X-ray images previously or subsequently acquired.DescriptionThe apparatus comprises a

  15. Using Coupled Harmonic Oscillators to Model Some Greenhouse Gas Molecules

    SciTech Connect (OSTI)

    Go, Clark Kendrick C.; Maquiling, Joel T.

    2010-07-28

    Common greenhouse gas molecules SF{sub 6}, NO{sub 2}, CH{sub 4}, and CO{sub 2} are modeled as harmonic oscillators whose potential and kinetic energies are derived. Using the Euler-Lagrange equation, their equations of motion are derived and their phase portraits are plotted. The authors use these data to attempt to explain the lifespan of these gases in the atmosphere.

  16. Density Functional Theory with Dissipation: Transport through Single Molecules

    SciTech Connect (OSTI)

    Kieron Burke

    2012-04-30

    A huge amount of fundamental research was performed on this grant. Most of it focussed on fundamental issues of electronic structure calculations of transport through single molecules, using density functional theory. Achievements were: (1) First density functional theory with dissipation; (2) Pseudopotential plane wave calculations with master equation; (3) Weak bias limit; (4) Long-chain conductance; and (5) Self-interaction effects in tunneling.

  17. Composition for detection of cell density signal molecule

    DOE Patents [OSTI]

    Schwarz, Richard I. (Oakland, CA)

    2001-01-01

    Disclosed herein is a novel proteinaceous cell density signal molecule (CDS), which is secreted by fibroblastic cells in culture, preferably tendon cells, and which provides a means by which the cells self-regulate their proliferation and the expression of differentiated function. CDS, and the antibodies which recognize them, are important for the development of diagnostics and treatments for injuries and diseases involving connective tissues, particularly tendon. Also disclosed are methods of production and use.

  18. Direct Measurement of Key Molecule Will Increase Accuracy of Combustion

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Models Measurement of Key Molecule Will Increase Accuracy of Combustion Models - Sandia Energy Energy Search Icon Sandia Home Locations Contact Us Employee Locator Energy & Climate Secure & Sustainable Energy Future Stationary Power Energy Conversion Efficiency Solar Energy Wind Energy Water Power Supercritical CO2 Geothermal Natural Gas Safety, Security & Resilience of the Energy Infrastructure Energy Storage Nuclear Power & Engineering Grid Modernization Battery Testing

  19. New Catalytic Approach Builds Molecules with Specific Functionality More

    Office of Science (SC) Website

    Safely and Efficiently | U.S. DOE Office of Science (SC) New Catalytic Approach Builds Molecules with Specific Functionality More Safely and Efficiently Basic Energy Sciences (BES) BES Home About Research Facilities Science Highlights Benefits of BES Funding Opportunities Basic Energy Sciences Advisory Committee (BESAC) Community Resources Contact Information Basic Energy Sciences U.S. Department of Energy SC-22/Germantown Building 1000 Independence Ave., SW Washington, DC 20585 P: (301)

  20. Polymer and small molecule based hybrid light source

    DOE Patents [OSTI]

    Choong, Vi-En (Carlsbad, CA); Choulis, Stelios (Nuremberg, DE); Krummacher, Benjamin Claus (Regensburg, DE); Mathai, Mathew (Monroeville, PA); So, Franky (Gainesville, FL)

    2010-03-16

    An organic electroluminescent device, includes: a substrate; a hole-injecting electrode (anode) coated over the substrate; a hole injection layer coated over the anode; a hole transporting layer coated over the hole injection layer; a polymer based light emitting layer, coated over the hole transporting layer; a small molecule based light emitting layer, thermally evaporated over the polymer based light emitting layer; and an electron-injecting electrode (cathode) deposited over the electroluminescent polymer layer.

  1. Subtask 2: Molecules, Materials, and Systems for Solar Electricity | ANSER

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Center | Argonne-Northwestern National Laboratory 2: Molecules, Materials, and Systems for Solar Electricity Home > Research > Subtask 2 The above figure depicts the structure of active polymer layers in organic solar cells. The above figure depicts the structure of active polymer layers in organic solar cells. ANSER Center research tests theory-driven ideas to understand at a fundamental level how photovoltaic cell performance is affected by nanoscale/mesoscale

  2. Structures of water molecules in carbon nanotubes under electric fields

    SciTech Connect (OSTI)

    Winarto,; Takaiwa, Daisuke; Yamamoto, Eiji; Yasuoka, Kenji

    2015-03-28

    Carbon nanotubes (CNTs) are promising for water transport through membranes and for use as nano-pumps. The development of CNT-based nanofluidic devices, however, requires a better understanding of the properties of water molecules in CNTs because they can be very different from those in the bulk. Using all-atom molecular dynamics simulations, we investigate the effect of axial electric fields on the structure of water molecules in CNTs having diameters ranging from (7,7) to (10,10). The water dipole moments were aligned parallel to the electric field, which increases the density of water inside the CNTs and forms ordered ice-like structures. The electric field induces the transition from liquid to ice nanotubes in a wide range of CNT diameters. Moreover, we found an increase in the lifetime of hydrogen bonds for water structures in the CNTs. Fast librational motion breaks some hydrogen bonds, but the molecular pairs do not separate and the hydrogen bonds reform. Thus, hydrogen bonds maintain the water structure in the CNTs, and the water molecules move collectively, decreasing the axial diffusion coefficient and permeation rate.

  3. Automated High Throughput Drug Target Crystallography

    SciTech Connect (OSTI)

    Rupp, B

    2005-02-18

    The molecular structures of drug target proteins and receptors form the basis for 'rational' or structure guided drug design. The majority of target structures are experimentally determined by protein X-ray crystallography, which as evolved into a highly automated, high throughput drug discovery and screening tool. Process automation has accelerated tasks from parallel protein expression, fully automated crystallization, and rapid data collection to highly efficient structure determination methods. A thoroughly designed automation technology platform supported by a powerful informatics infrastructure forms the basis for optimal workflow implementation and the data mining and analysis tools to generate new leads from experimental protein drug target structures.

  4. Single Molecule Switches and Molecular Self-Assembly: Low Temperature STM Investigations and Manipulations

    SciTech Connect (OSTI)

    Iancu, Violeta

    2006-08-01

    This dissertation is devoted to single molecule investigations and manipulations of two porphyrin-based molecules, chlorophyll-a and Co-popphyrin. The molecules are absorbed on metallic substrates and studied at low temperatures using a scanning tunneling microscope. The electronic, structural and mechanical properties of the molecules are investigated in detail with atomic level precision. Chlorophyll-a is the key ingredient in photosynthesis processes while Co-porphyrin is a magnetic molecule that represents the recent emerging field of molecular spintronics. Using the scanning tunneling microscope tip and the substrate as electrodes, and the molecules as active ingredients, single molecule switches made of these two molecules are demonstrated. The first switch, a multiple and reversible mechanical switch, is realized by using chlorophyll-a where the energy transfer of a single tunneling electron is used to rotate a C-C bond of the molecule's tail on a Au(111) surface. Here, the det

  5. Novel nuclear magnetic resonance techniques for studying biological molecules

    SciTech Connect (OSTI)

    Laws, David D.

    2000-06-01

    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone ({phi}/{psi}) dihedral angles by comparing experimentally determined {sup 13}C{sub a}, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of {alpha}-helical and {beta}-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly {beta}-sheet.

  6. BEAM TRANSPORT AND STORAGE WITH COLD NEUTRAL ATOMS AND MOLECULES

    SciTech Connect (OSTI)

    Walstrom, Peter L.

    2012-05-15

    A large class of cold neutral atoms and molecules is subject to magnetic field-gradient forces. In the presence of a field, hyperfine atomic states are split into several Zeeman levels. The slopes of these curves vs. field are the effective magnetic moments. By means of optical pumping in a field, Zeeman states of neutral lithium atoms and CaH molecules with effective magnetic moments of nearly {+-} one Bohr magneton can be selected. Particles in Zeeman states for which the energy increases with field are repelled by increasing fields; particles in states for which the energy decreases with field are attracted to increasing fields. For stable magnetic confinement, field-repelled states are required. Neutral-particle velocities in the present study are on the order of tens to hundreds of m/s and the magnetic fields needed for transport and injection are on the order of in the range of 0.01-1T. Many of the general concepts of charged-particle beam transport carry over into neutral particle spin-force optics, but with important differences. In general, the role of bending dipoles in charged particle optics is played by quadrupoles in neutral particle optics; the role of quadrupoles is played by sextupoles. The neutralparticle analog of charge-exchange injection into storage rings is the use of lasers to flip the state of particles from field-seeking to field-repelled. Preliminary tracking results for two neutral atom/molecule storage ring configurations are presented. It was found that orbit instabilities limit the confinment time in a racetrack-shaped ring with discrete magnetic elements with drift spaces between them; stable behavior was observed in a toroidal ring with a continuous sextupole field. An alternative concept using a linear sextupole or octupole channel with solenoids on the ends is presently being considered.

  7. Molecular Design of Branched and Binary Molecules at Ordered Interfaces

    SciTech Connect (OSTI)

    Kirsten Larson Genson

    2005-12-27

    This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross-sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformation which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.

  8. In and out of the minor groove: interaction of an AT-rich DNA with the drug CD27

    SciTech Connect (OSTI)

    Acosta-Reyes, Francisco J.; Dardonville, Christophe; Koning, Harry P. de; Natto, Manal; Subirana, Juan A.; Campos, J. Lourdes

    2014-06-01

    New features of an antiprotozoal DNA minor-groove binding drug, which acts as a cross-linking agent, are presented. It also fills the minor groove of DNA completely and prevents the access of proteins. These features are also expected for other minor-groove binding drugs when associated with suitable DNA targets. The DNA of several pathogens is very rich in AT base pairs. Typical examples include the malaria parasite Plasmodium falciparum and the causative agents of trichomoniasis and trypanosomiases. This fact has prompted studies of drugs which interact with the minor groove of DNA, some of which are used in medical practice. Previous studies have been performed almost exclusively with the AATT sequence. New features should be uncovered through the study of different DNA sequences. In this paper, the crystal structure of the complex of the DNA duplex d(AAAATTTT){sub 2} with the dicationic drug 4, 4?-bis(imidazolinylamino)diphenylamine (CD27) is presented. The drug binds to the minor groove of DNA as expected, but it shows two new features that have not previously been described: (i) the drugs protrude from the DNA and interact with neighbouring molecules, so that they may act as cross-linking agents, and (ii) the drugs completely cover the whole minor groove of DNA and displace bound water. Thus, they may prevent the access to DNA of proteins such as AT-hook proteins. These features are also expected for other minor-groove binding drugs when associated with all-AT DNA. These findings allow a better understanding of this family of compounds and will help in the development of new, more effective drugs. New data on the biological interaction of CD27 with the causative agent of trichomoniasis, Trichomonas vaginalis, are also reported.

  9. Entropy-based separation of linear chain molecules by exploiting

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    differences in the saturation capacities in cage-type zeolites | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Entropy-based separation of linear chain molecules by exploiting differences in the saturation capacities in cage-type zeolites Previous Next List Rajamani Krishna, Jasper M. van Baten, Sep. Purif. Technol., 76, 325-330 (2011) DOI: 10.1016/j.seppur.2010.10.023 Full-size image (26 K) Abstract: For zeolites such as CHA, LTA, DDR, ERI, AFX, and TSC

  10. Deterministically Polarized Fluorescence from Single Dye Molecules Aligned in Liquid Crystal Host

    SciTech Connect (OSTI)

    Lukishova, S.G.; Schmid, A.W.; Knox, R.; Freivald, P.; Boyd, R. W.; Stroud, Jr., C. R.; Marshall, K.L.

    2005-09-30

    We demonstrated for the first time to our konwledge deterministically polarized fluorescence from single dye molecules. Planar aligned nematic liquid crystal hosts provide deterministic alignment of single dye molecules in a preferred direction.

  11. Recent developments with metalloprotease inhibitor class of drug candidates for Botulinum neurotoxins

    SciTech Connect (OSTI)

    Kumar, Gyanendra; Swaminathan, Subramanyam

    2015-03-01

    Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are also potential biological warfare and bioterrorism agents due to their high toxicity and ease of preparation. On the other hand BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and with that the chances of accidental overdose are increasing. And despite the potential damage they could cause to human health, there are no post-intoxication drugs available so far. But progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been determined, and these are enabling structure-based drug discovery possible. High throughput assays have also been designed to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments and the future challenges in drug discovery for Botulinum neurotoxins.

  12. Recent developments with metalloprotease inhibitor class of drug candidates for Botulinum neurotoxins

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kumar, Gyanendra; Swaminathan, Subramanyam

    2015-03-01

    Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are also potential biological warfare and bioterrorism agents due to their high toxicity and ease of preparation. On the other hand BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and with that the chances of accidental overdose are increasing. And despite the potential damage they could cause to human health, there are no post-intoxication drugs available so far. But progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been determined, andmore » these are enabling structure-based drug discovery possible. High throughput assays have also been designed to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments and the future challenges in drug discovery for Botulinum neurotoxins.« less

  13. DEUTERATED MOLECULES IN ORION KL FROM HERSCHEL/HIFI

    SciTech Connect (OSTI)

    Neill, Justin L.; Crockett, Nathan R.; Bergin, Edwin A.; Pearson, John C.; Xu, Li-Hong

    2013-11-10

    We present a comprehensive study of the deuterated molecules detected in the fullband HIFI survey of the Orion Kleinmann-Low nebula (Orion KL) region. Ammonia, formaldehyde, and methanol and their singly deuterated isotopologues are each detected through numerous transitions in this survey with a wide range in optical depths and excitation conditions. In conjunction with a recent study of the abundance of HDO and H{sub 2}O in Orion KL, this study yields the best constraints on deuterium fractionation in an interstellar molecular cloud to date. As previous studies have found, both the Hot Core and Compact Ridge regions within Orion KL contain significant abundances of deuterated molecules, suggesting an origin in cold grain mantles. In the Hot Core, we find that ammonia is roughly a factor of two more fractionated than water. In the Compact Ridge, meanwhile, we find similar deuterium fractionation in water, formaldehyde, and methanol, with D/H ratios of (2-8) × 10{sup –3}. The [CH{sub 2}DOH]/[CH{sub 3}OD] ratio in the Compact Ridge is found to be 1.2 ± 0.3. The Hot Core generally has lower deuterium fractionation than the Compact Ridge, suggesting a slightly warmer origin, or a greater contribution from warm gas phase chemistry.

  14. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print Tuesday, 23 June 2015 13:00 The cancer drug...

  15. Coherent Anti-Stokes Raman Scattering Spectroscopy of Single Molecules in Solution

    SciTech Connect (OSTI)

    Sunney Xie, Wei Min, Chris Freudiger, Sijia Lu

    2012-01-18

    During this funding period, we have developed two breakthrough techniques. The first is stimulated Raman scattering microscopy, providing label-free chemical contrast for chemical and biomedical imaging based on vibrational spectroscopy. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. We developed a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We demonstrated a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis. This technology offers exciting prospect for medical imaging. The second technology we developed is stimulated emission microscopy. Many chromophores, such as haemoglobin and cytochromes, absorb but have undetectable fluorescence because the spontaneous emission is dominated by their fast non-radiative decay. Yet the detection of their absorption is difficult under a microscope. We use stimulated emission, which competes effectively with the nonradiative decay, to make the chromophores detectable, as a new contrast mechanism for optical microscopy. We demonstrate a variety of applications of stimulated emission microscopy, such as visualizing chromoproteins, non-fluorescent variants of the green fluorescent protein, monitoring lacZ gene expression with a chromogenic reporter, mapping transdermal drug distribu- tions without histological sectioning, and label-free microvascular imaging based on endogenous contrast of haemoglobin. For all these applications, sensitivity is orders of magnitude higher than for spontaneous emission or absorption contrast, permitting nonfluorescent reporters for molecular imaging. Although we did not accomplish the original goal of detecting single-molecule by CARS, our quest for high sensitivity of nonlinear optical microscopy paid off in providing the two brand new enabling technologies. Both techniques were greatly benefited from the use of high frequency modulation for microscopy, which led to orders of magnitude increase in sensitivity. Extensive efforts have been made on optics and electronics to accomplish these breakthroughs.

  16. Transport behavior of water molecules through two-dimensional nanopores

    SciTech Connect (OSTI)

    Zhu, Chongqin; Li, Hui; Meng, Sheng

    2014-11-14

    Water transport through a two-dimensional nanoporous membrane has attracted increasing attention in recent years thanks to great demands in water purification and desalination applications. However, few studies have been reported on the microscopic mechanisms of water transport through structured nanopores, especially at the atomistic scale. Here we investigate the microstructure of water flow through two-dimensional model graphene membrane containing a variety of nanopores of different size by using molecular dynamics simulations. Our results clearly indicate that the continuum flow transits to discrete molecular flow patterns with decreasing pore sizes. While for pores with a diameter ?15 Å water flux exhibits a linear dependence on the pore area, a nonlinear relationship between water flux and pore area has been identified for smaller pores. We attribute this deviation from linear behavior to the presence of discrete water flow, which is strongly influenced by the water-membrane interaction and hydrogen bonding between water molecules.

  17. Reaction mechanism studies of unsaturated molecules using photofragment translational spectroscopy

    SciTech Connect (OSTI)

    Longfellow, C.A. |

    1996-05-01

    A number of molecules have been studied using the technique of photofragment translational spectroscopy. In Chapter One a brief introduction to the experimental technique is given. In Chapter Two the infrared multiphoton dissociation (IRMPD) of acetic acid is discussed. Carbon dioxide and methane were observed for the first time as products from dissociation under collisionless conditions. Chapter Three relates an IRMPD experiment of hexafluoropropene. The predominant channel produces CFCF{sub 3} or C{sub 2}F{sub 4} and CF{sub 2}, with the heavier species undergoing further dissociation to two CF{sub 2} fragments. In Chapter Four the ultraviolet (UV) dissociation of hexafluoropropene is investigated. Chapter Five explores the IRMPD of octafluoro-1-butene and octafluoro-2-butene.

  18. Oligomycin frames a common drug-binding site in the ATP synthase

    SciTech Connect (OSTI)

    Symersky, Jindrich; Osowski, Daniel; Walters, D. Eric; Mueller, David M.

    2015-12-01

    We report the high-resolution (1.9 {angstrom}) crystal structure of oligomycin bound to the subunit c10 ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c10 ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common 'drug-binding site.' We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

  19. Method for loading lipid like vesicles with drugs of other chemicals

    DOE Patents [OSTI]

    Mehlhorn, Rolf Joachim (Richmond, CA)

    1998-01-01

    A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures.

  20. Method for loading lipid like vesicles with drugs of other chemicals

    DOE Patents [OSTI]

    Mehlhorn, R.J.

    1998-06-09

    A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures. 2 figs.

  1. Non-destructively shattered mesoporous silica for protein drug...

    Office of Scientific and Technical Information (OSTI)

    Non-destructively shattered mesoporous silica for protein drug delivery Citation Details In-Document Search Title: Non-destructively shattered mesoporous silica for protein drug ...

  2. Food and Drug Administration White Oak Campus Environmental Stewardshi...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Food and Drug Administration White Oak Campus Environmental Stewardship and Cost Savings FEMP ESPC Success Story on water conservation and green energy at the Food and Drug ...

  3. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein...

  4. DOE Laboratories Help Develop Promising New Cancer Fighting Drug...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib DOE Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib August 18, 2011 - 1:03pm ...

  5. Observing a coherent superposition of an atom and a molecule

    SciTech Connect (OSTI)

    Dowling, Mark R. [School of Physical Sciences, University of Queensland, St. Lucia, Queensland 4072 (Australia); Bartlett, Stephen D. [School of Physics, University of Sydney, Sydney, New South Wales 2006 (Australia); Rudolph, Terry [Optics Section, Blackett Laboratory, Imperial College London, London SW7 2BW (United Kingdom); Institute for Mathematical Sciences, Imperial College London, London SW7 2BW (United Kingdom); Spekkens, Robert W. [Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA (United Kingdom)

    2006-11-15

    We demonstrate that it is possible, in principle, to perform a Ramsey-type interference experiment to exhibit a coherent superposition of a single atom and a diatomic molecule. This gedanken experiment, based on the techniques of Aharonov and Susskind [Phys. Rev. 155, 1428 (1967)], explicitly violates the commonly accepted superselection rule that forbids coherent superpositions of eigenstates of differing atom number. A Bose-Einstein condensate plays the role of a reference frame that allows for coherent operations analogous to Ramsey pulses. We also investigate an analogous gedanken experiment to exhibit a coherent superposition of a single boson and a fermion, violating the commonly accepted superselection rule forbidding coherent superpositions of states of differing particle statistics. In this case, the reference frame is realized by a multimode state of many fermions. This latter case reproduces all of the relevant features of Ramsey interferometry, including Ramsey fringes over many repetitions of the experiment. However, the apparent inability of this proposed experiment to produce well-defined relative phases between two distinct systems each described by a coherent superposition of a boson and a fermion demonstrates that there are additional, outstanding requirements to fully 'lift' the univalence superselection rule.

  6. Continuum model for chiral induced spin selectivity in helical molecules

    SciTech Connect (OSTI)

    Medina, Ernesto; González-Arraga, Luis A.; Finkelstein-Shapiro, Daniel; Mujica, Vladimiro; Berche, Bertrand

    2015-05-21

    A minimal model is exactly solved for electron spin transport on a helix. Electron transport is assumed to be supported by well oriented p{sub z} type orbitals on base molecules forming a staircase of definite chirality. In a tight binding interpretation, the spin-orbit coupling (SOC) opens up an effective ?{sub z} ? ?{sub z} coupling via interbase p{sub x,y} ? p{sub z} hopping, introducing spin coupled transport. The resulting continuum model spectrum shows two Kramers doublet transport channels with a gap proportional to the SOC. Each doubly degenerate channel satisfies time reversal symmetry; nevertheless, a bias chooses a transport direction and thus selects for spin orientation. The model predicts (i) which spin orientation is selected depending on chirality and bias, (ii) changes in spin preference as a function of input Fermi level and (iii) back-scattering suppression protected by the SO gap. We compute the spin current with a definite helicity and find it to be proportional to the torsion of the chiral structure and the non-adiabatic Aharonov-Anandan phase. To describe room temperature transport, we assume that the total transmission is the result of a product of coherent steps.

  7. Spin-dependent electron transport in zinc- and manganese-doped adenine molecules

    SciTech Connect (OSTI)

    Simchi, Hamidreza; Esmaeilzadeh, Mahdi Mazidabadi, Hossein

    2014-01-28

    The spin-dependent electron transport properties of zinc- and manganese-doped adenine molecules connected to zigzag graphene leads are studied in the zero bias regime using the non-equilibrium Green's function method. The conductance of the adenine molecule increased and became spin-dependent when a zinc or manganese atom was doped into the molecules. The effects of a transverse electric field on the spin-polarization of the transmitted electrons were investigated and the spin-polarization was controlled by changing the transverse electric field. Under the presence of a transverse electric field, both the zinc- and manganese-doped adenine molecules acted as spin-filters. The maximum spin-polarization of the manganese-doped adenine molecule was greater than the molecule doped with zinc.

  8. Matrix Infrared Spectroscopic and Computational Investigations of Novel Small Uranium Containing Molecules - Final Technical Report

    SciTech Connect (OSTI)

    Andrews, Lester

    2014-10-17

    Direct reactions of f-element uranium, thorium and lanthanide metal atoms were investigated with small molecules. These metal atoms were generated by laser ablation and mixed with the reagent molecules then condensed with noble gases at 4K. The products were analyzed by absorption of infrared light to measure vibrational frequencies which were confirmed by quantum chemical calculations. We have learned more about the reactivity of uranium atoms with common molecules, which will aid in the develolpment of further applications of uranium.

  9. Pre-Designed Single-Molecule Traps for CO2 Capture | Center for Gas

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Pre-Designed Single-Molecule Traps for CO2 Capture

  10. THE ORIGIN OF COMPLEX ORGANIC MOLECULES IN PRESTELLAR CORES

    SciTech Connect (OSTI)

    Vastel, C.; Ceccarelli, C.; Lefloch, B.; Bachiller, R.

    2014-11-01

    Complex organic molecules (COMs) have been detected in a variety of environments including cold prestellar cores. Given the low temperatures of these objects, these detections challenge existing models. We report here new observations toward the prestellar core L1544. They are based on an unbiased spectral survey of the 3 mm band at the IRAM 30 m telescope as part of the Large Program ASAI. The observations allow us to provide a full census of the oxygen-bearing COMs in this source. We detected tricarbon monoxide, methanol, acetaldehyde, formic acid, ketene, and propyne with abundances varying from 5 × 10{sup –11} to 6 × 10{sup –9}. The non-LTE analysis of the methanol lines shows that they are likely emitted at the border of the core at a radius of ?8000 AU, where T ? 10 K and n {sub H{sub 2}} ?2 × 10{sup 4} cm{sup –3}. Previous works have shown that water vapor is enhanced in the same region because of the photodesorption of water ices. We propose that a non-thermal desorption mechanism is also responsible for the observed emission of methanol and COMs from the same layer. The desorbed oxygen and a small amount of desorbed methanol and ethene are enough to reproduce the abundances of tricarbon monoxide, methanol, acetaldehyde, and ketene measured in L1544. These new findings open the possibility that COMs in prestellar cores originate in a similar outer layer rather than in the dense inner cores, as previously assumed, and that their formation is driven by the non-thermally desorbed species.

  11. Organic molecules deposited on graphene: A computational investigation of self-assembly and electronic structure

    SciTech Connect (OSTI)

    Oliveira, I. S. S. de; Miwa, R. H.

    2015-01-28

    We use ab initio simulations to investigate the adsorption and the self-assembly processes of tetracyanoquinodimethane (TCNQ), tetrafluoro-tetracyanoquinodimethane (F4-TCNQ), and tetrasodium 1,3,6,8-pyrenetetrasulfonic acid (TPA) on the graphene surface. We find that there are no chemical bonds at the molecule–graphene interface, even at the presence of grain boundaries on the graphene surface. The molecules bond to graphene through van der Waals interactions. In addition to the molecule–graphene interaction, we performed a detailed study of the role played by the (lateral) molecule–molecule interaction in the formation of the, experimentally verified, self-assembled layers of TCNQ and TPA on graphene. Regarding the electronic properties, we calculate the electronic charge transfer from the graphene sheet to the TCNQ and F4-TCNQ molecules, leading to a p-doping of graphene. Meanwhile, such charge transfer is reduced by an order of magnitude for TPA molecules on graphene. In this case, it is not expected a significant doping process upon the formation of self-assembled layer of TPA molecules on the graphene sheet.

  12. Method and apparatus for passive optical dosimeter comprising caged dye molecules

    DOE Patents [OSTI]

    Sandison, David R. (Edgewood, NM)

    2001-07-03

    A new class of ultraviolet dosimeters is made possible by exposing caged dye molecules, which generate a dye molecule on exposure to ultraviolet radiation, to an exterior environment. Applications include sunburn monitors, characterizing the UV exposure history of UV-sensitive materials, especially including structural plastics, and use in disposable `one-use` optical equipment, especially medical devices.

  13. Electrochemical detection of single molecules using abiotic nanopores having electrically tunable dimensions

    DOE Patents [OSTI]

    Sansinena, Jose-Maria (Los Alamos, NM); Redondo, Antonio (Los Alamos, NM); Olazabal, Virginia (Los Alamos, NM); Hoffbauer, Mark A. (Los Alamos, NM); Akhadov, Elshan A. (Los Alamos, NM)

    2009-12-29

    A barrier structure for use in an electrochemical stochastic membrane sensor for single molecule detection. The sensor is based upon inorganic nanopores having electrically tunable dimensions. The inorganic nanopores are formed from inorganic materials and an electrically conductive polymer. Methods of making the barrier structure and sensing single molecules using the barrier structure are also described.

  14. Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules

    DOE Patents [OSTI]

    Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E

    2014-01-14

    Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

  15. Optically generated ultrasound for enhanced drug delivery

    DOE Patents [OSTI]

    Visuri, Steven R. (Livermore, CA); Campbell, Heather L. (Baltimore, MD); Da Silva, Luiz (Danville, CA)

    2002-01-01

    High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

  16. Ethics and Drug-Free Certification Form

    Office of Environmental Management (EM)

    NEW EMPLOYEE ORIENTATION ETHICS BRIEFING CERTIFICATION OF ______________________________ (Print Name) I hereby certify that I have reviewed the New Employee Orientation information on the Standards of Ethical Conduct for Employees in the Executive Branch, 5 C.F. R. Part 2635, and the DOE 3792.3 Drug-Free Federal Workplace Testing Program. Further, I certify that I understand that all Department of Energy employees, other than Special Government Employees, must obtain prior written approval from

  17. Secretary Bodman's Memorandum Regarding Drug Testing at DOE | Department of

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Secretary Bodman's Memorandum Regarding Drug Testing at DOE Secretary Bodman's Memorandum Regarding Drug Testing at DOE September 14, 2007 In consideration of the report on the Task Force Review of the Departmental Personnel Security Program (February 2007), the Secretary has made the following decisions regarding drug testing for Department of Energy (DOE) positions that require access authorizations (security clearances). PDF icon Decisions Regarding Drug Testing for DOE Positions

  18. Forensic Drug Testing Custody and Control Form | Department of Energy

    Broader source: Energy.gov (indexed) [DOE]

    DOE contractors must use the Forensic Drug Testing Custody and Control Form (the look-a-like form) for their drug testing programs to comply with the requirements in 10 CFR part 707 and provide consistency in their drug testing programs. This form is currently available at HHS-certified laboratories. PDF icon Forensic Drug Testing Custody and Control Form More Documents & Publications DOE F 470.7 Comments on Supplemental Notice of Proposed Rulemaking for Alternative Efficiency Determination

  19. Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Department of Energy Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC PDF icon Intergrated Drug Testing System, PIA, Bechtel Jacobs C ompany, LLC More Documents & Publications Electronic Document Management System PIA, BechtelJacobs Company, LLC Dosimetry Records System PIA, bechtel Jacobs Company, LLC Pension Estimate System PIA, Bechtel

  20. Matrix, Drug Testing for DOE Security Clearance - September 1, 2011 |

    Office of Environmental Management (EM)

    Department of Energy Matrix, Drug Testing for DOE Security Clearance - September 1, 2011 Matrix, Drug Testing for DOE Security Clearance - September 1, 2011 September 1, 2011 The following matrix identifies those individuals required to have a current negative drug test as a prerequisite for being processed for a security clearance The following matrix identifies those individuals required to have a current negative drug test as a prerequisite for being processed for a security clearance. A

  1. Resonance reactions and enhancement of weak interactions in collisions of cold molecules

    SciTech Connect (OSTI)

    Flambaum, V. V.; Ginges, J. S. M. [School of Physics, University of New South Wales, Sydney 2052 (Australia)

    2006-08-15

    With the creation of ultracold atoms and molecules, a new type of chemistry - 'resonance' chemistry - emerges: chemical reactions can occur when the energy of colliding atoms and molecules matches a bound state of the combined molecule (Feshbach resonance). This chemistry is rather similar to reactions that take place in nuclei at low energies. In this paper we suggest some problems for future experimental and theoretical work related to the resonance chemistry of ultracold molecules. Molecular Bose-Einstein condensates are particularly interesting because in this system collisions and chemical reactions are extremely sensitive to weak fields; also, a preferred reaction channel may be enhanced due to a finite number of final states. The sensitivity to weak fields arises due to the high density of narrow compound resonances and the macroscopic number of molecules with kinetic energy E=0 (in the ground state of a mean-field potential). The high sensitivity to the magnetic field may be used to measure the distribution of energy intervals, widths, and magnetic moments of compound resonances and study the onset of quantum chaos. A difference in the production rate of right-handed and left-handed chiral molecules may be produced by external electric E and magnetic B fields and the finite width {gamma} of the resonance (correlation {gamma}E{center_dot}B). The same effect may be produced by the parity-violating energy difference in chiral molecules.

  2. Growth of Ammonium Bisulfate Clusters by Adsorption of Oxygenated Organic Molecules

    SciTech Connect (OSTI)

    DePalma, Joseph W.; Wang, Jian; Wexler, Anthony S.; Johnston, Murray V.

    2015-10-21

    Quantum chemical calculations were employed to model the interactions of the [(NH4+)4(HSO4-)4] ammonium bisulfate cluster with one or more molecular products of monoterpene oxidation. A strong interaction was found between the bisulfate ion of the cluster and a carboxylic acid, aldehyde or ketone functionality of the organic molecule. Free energies of adsorption for carboxylic acids were in the -70 to -73 kJ/mol range, while those for aldehydes and ketones were in the -46 to -50 kJ/mol range. These values suggest that a small ambient ammonium bisulfate cluster, such as the [(NH4+)4(SO4-)4] cluster, is able to adsorb an oxygenated organic molecule. Although adsorption of the first molecule is highly favorable, adsorption of subsequent molecules is not, suggesting that sustained uptake of organic molecules does not occur, and thus is not a pathway for continuing growth of the cluster. This result is consistent with ambient measurements showing that particles below ~1 nm grow slowly, while those above 1 nm grow at an increasing rate presumably due to a lower surface energy barrier enabling the uptake of organic molecules. This work provides insight into the molecular level interactions which affect sustained cluster growth by uptake of organic molecules.

  3. Growth of Ammonium Bisulfate Clusters by Adsorption of Oxygenated Organic Molecules

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    DePalma, Joseph W.; Wang, Jian; Wexler, Anthony S.; Johnston, Murray V.

    2015-10-21

    Quantum chemical calculations were employed to model the interactions of the [(NH4+)4(HSO4-)4] ammonium bisulfate cluster with one or more molecular products of monoterpene oxidation. A strong interaction was found between the bisulfate ion of the cluster and a carboxylic acid, aldehyde or ketone functionality of the organic molecule. Free energies of adsorption for carboxylic acids were in the -70 to -73 kJ/mol range, while those for aldehydes and ketones were in the -46 to -50 kJ/mol range. These values suggest that a small ambient ammonium bisulfate cluster, such as the [(NH4+)4(SO4-)4] cluster, is able to adsorb an oxygenated organic molecule.more » Although adsorption of the first molecule is highly favorable, adsorption of subsequent molecules is not, suggesting that sustained uptake of organic molecules does not occur, and thus is not a pathway for continuing growth of the cluster. This result is consistent with ambient measurements showing that particles below ~1 nm grow slowly, while those above 1 nm grow at an increasing rate presumably due to a lower surface energy barrier enabling the uptake of organic molecules. This work provides insight into the molecular level interactions which affect sustained cluster growth by uptake of organic molecules.« less

  4. Drug-Free Federal Workplace Testing Implementation Program

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1988-07-29

    The order provides guidance and policy for the administration, application and implementation of the DOE Drug-free Federal Workplace Plan and other regulations that facilitate the maintenance of a drug-free Federal workplace through the establishment of programs to test for the use of illegal drugs. Chg 1, dated 8-21-92

  5. Controlling the optical dipole force for molecules with field-induced alignment

    SciTech Connect (OSTI)

    Purcell, S. M.; Barker, P. F.

    2010-09-15

    We measure the role of field-induced alignment on the dipole force for molecules using a single focused nonresonant laser beam. We show that through the alignment process we can modify the effective polarizability by field polarization and thus control the center-of-mass motion of the molecule. We observe a maximum change of 20% in the dipole force on CS{sub 2} molecules when changing from linearly to circularly polarized light. Additionally, the effect of the dipole force on different vibrational states is also studied.

  6. Artificial molecules that switch "handedness" at light-speed

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Artificial molecules that switch "handedness" Artificial molecules that switch "handedness" at light-speed Researchers create the first artificial molecules whose chirality can be rapidly switched from a right-handed to a left-handed orientation with a beam of light. July 10, 2012 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience,

  7. Mechanism of Angular Momentum Exchange between Molecules and Laguerre-Gaussian Beams

    SciTech Connect (OSTI)

    Alexandrescu, Adrian; Cojoc, Dan; Fabrizio, Enzo Di

    2006-06-23

    We derive the interaction Hamiltonian between a diatomic molecule and a Laguerre-Gaussian beam under the assumption of a small spread of the center of mass wave function of the molecule in comparison with the beam waist. Considering the dynamical variables of the center of mass, vibrational, rotational, and electronic motion, we show that, within the electronic dipole approximation, the orbital angular momentum of the field couples with the rotational and electronic motion. The changes in the transition probabilities and selection rules induced by the field orbital angular momentum and the applicability of the derived interaction mechanisms for polyatomic molecules are discussed.

  8. AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery

    SciTech Connect (OSTI)

    Tsai, Yingssu; McPhillips, Scott E.; González, Ana; McPhillips, Timothy M.; Zinn, Daniel; Cohen, Aina E.; Feese, Michael D.; Bushnell, David; Tiefenbrunn, Theresa; Stout, C. David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O.; Soltis, S. Michael

    2013-05-01

    New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully demonstrated. This workflow was run once on the same 96 samples that the group had examined manually and the workflow cycled successfully through all of the samples, collected data from the same samples that were selected manually and located the same peaks of unmodeled density in the resulting difference Fourier maps.

  9. From Artificial Atoms to Nanocrystal Molecules: Preparation and Properties of More Complex Nanostructures

    SciTech Connect (OSTI)

    Choi, Charina L; Alivisatos, A Paul

    2009-10-20

    Quantum dots, which have found widespread use in fields such as biomedicine, photovoltaics, and electronics, are often called artificial atoms due to their size-dependent physical properties. Here this analogy is extended to consider artificial nanocrystal molecules, formed from well-defined groupings of plasmonically or electronically coupled single nanocrystals. Just as a hydrogen molecule has properties distinct from two uncoupled hydrogen atoms, a key feature of nanocrystal molecules is that they exhibit properties altered from those of the component nanoparticles due to coupling. The nature of the coupling between nanocrystal atoms and its response to vibrations and deformations of the nanocrystal molecule bonds are of particular interest. We discuss synthetic approaches, predicted and observed physical properties, and prospects and challenges toward this new class of materials.

  10. Ionization of oriented carbonyl sulfide molecules by intense circularly polarized laser pulses

    SciTech Connect (OSTI)

    Dimitrovski, Darko; Abu-samha, Mahmoud; Madsen, Lars Bojer; Filsinger, Frank; Meijer, Gerard; Kuepper, Jochen [Lundbeck Foundation Theoretical Center for Quantum System Research, Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin (Germany); Holmegaard, Lotte; Kalhoej, Line [Department of Chemistry, Aarhus University, DK-8000 Aarhus C (Denmark); Nielsen, Jens H. [Department of Physics, Aarhus University, DK-8000 Aarhus C (Denmark); Stapelfeldt, Henrik [Department of Chemistry, Aarhus University, DK-8000 Aarhus C (Denmark); Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C (Denmark)

    2011-02-15

    We present combined experimental and theoretical results on strong-field ionization of oriented carbonyl sulfide molecules by circularly polarized laser pulses. The obtained molecular frame photoelectron angular distributions show pronounced asymmetries perpendicular to the direction of the molecular electric dipole moment. These findings are explained by a tunneling model invoking the laser-induced Stark shifts associated with the dipoles and polarizabilities of the molecule and its unrelaxed cation. The focus of the present article is to understand the strong-field ionization of one-dimensionally-oriented polar molecules, in particular asymmetries in the emission direction of the photoelectrons. In the following article [Phys. Rev. A 83, 023406 (2011)] the focus is to understand strong-field ionization from three-dimensionally-oriented asymmetric top molecules, in particular the suppression of electron emission in nodal planes of molecular orbitals.

  11. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

    SciTech Connect (OSTI)

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in Tuscany, provides an avenue for scientists from different disciplines to interact and brainstorm and promotes cross-disciplinary collaborations directed toward compelling biological problems.

  12. Tracing the structure of asymmetric molecules from high-order harmonic generation

    SciTech Connect (OSTI)

    Chen Yanjun; Zhang, Bing

    2011-11-15

    We investigate high-order harmonic generation (HHG) from asymmetric molecules exposed to intense laser fields. We show that the emissions of odd and even harmonics depend differently on the orientation angle, the internuclear distance, as well as the effective charge. This difference mainly comes from different roles of intramolecular interference in the HHG of odd and even harmonics. These roles map the structure of the asymmetric molecule to the odd vs even HHG spectra.

  13. Inorganic-Organic Molecules and Solids with Nanometer-Sized Pores

    SciTech Connect (OSTI)

    Maverick, Andrew W.

    2011-12-17

    We are constructing porous inorganic-organic hybrid molecules and solids, many of which contain coordinatively unsaturated metal centers. In this work, we use multifunctional ���²-diketone ligands as �¢����building blocks�¢��� to prepare extended-solid and molecular porous materials that are capable of reacting with a variety of guest molecules.

  14. Laser Induced Nuclear Fusion, LINF, In Muonic Molecules With Ultrashort Super Intense Laser Fields

    SciTech Connect (OSTI)

    Bandrauk, Andre D.; Paramonov, Gennady K.

    2010-02-02

    Muonium molecules where muons replace electrons increase the stability of molecules to ionization at superhigh intensities, I>10{sup 20} W/cm{sup 2}. We show furthermore from numerical simulations that in the nonsymmetric series, pdu, dtu, ptu, the permanent dipole moments can be used to enhance LINF, Laser Induced Nuclear Fusion by laser induced recollision of the light nucleus with the heavier nucleus.

  15. Molecule@MOF: A New Class of Electronic Materials. (Conference) | SciTech

    Office of Scientific and Technical Information (OSTI)

    Connect Molecule@MOF: A New Class of Electronic Materials. Citation Details In-Document Search Title: Molecule@MOF: A New Class of Electronic Materials. Abstract not provided. Authors: Talin, Albert Alec ; Foster, Michael E. ; Stavila, Vitalie ; Leonard, Francois Leonard ; Spataru, Dan Catalin ; Allendorf, Mark D. ; Ford, Alexandra Caroline ; El Gabaly Marquez, Farid Publication Date: 2014-09-01 OSTI Identifier: 1241683 Report Number(s): SAND2014-18122PE 537746 DOE Contract Number:

  16. Viable Single-Molecule Diodes | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Viable Single-Molecule Diodes Basic Energy Sciences (BES) BES Home About Research Facilities Science Highlights Benefits of BES Funding Opportunities Basic Energy Sciences Advisory Committee (BESAC) Community Resources Contact Information Basic Energy Sciences U.S. Department of Energy SC-22/Germantown Building 1000 Independence Ave., SW Washington, DC 20585 P: (301) 903-3081 F: (301) 903-6594 E: Email Us More Information » 11.01.15 Viable Single-Molecule Diodes Major milestone in molecular

  17. [alpha]E-catenin is an autoinhibited molecule that coactivates vinculin

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect [alpha]E-catenin is an autoinhibited molecule that coactivates vinculin Citation Details In-Document Search Title: [alpha]E-catenin is an autoinhibited molecule that coactivates vinculin Authors: Choi, Hee-Jung ; Pokutta, Sabine ; Cadwell, Gregory W. ; Bobkov, Andrey A. ; Bankston, Laurie A. ; Liddington, Robert C. ; Weis, William I. [1] ; Sanford-Burnham) [2] + Show Author Affiliations (Stanford-MED) ( Publication Date: 2012-10-02 OSTI Identifier: 1051867

  18. DRUG TESING PANEL & CUTOFF CONCENTRATIONS

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    DRUG TESTING PANEL & CUTOFF CONCENTRATIONS Initial Test Analyte Initial Test Cutoff Concentration Confirmatory Test Analyte Confirmatory Test Cutoff Concentration Marijuana Metabolites 50 ng/mL THCA \1\ 15 ng/mL Cocaine Metabolites 150 ng/mL Benzoylecgonine 100 ng/mL Codeine 2000 ng/mL Opiate Metabolites: Codeine/Morphine \2\ 2000 ng/mL Morphine 2000 ng/mL 6-Acetylmorphine (Heroine) 10 ng/mL 6-Acetylmorphine 10 ng/mL Phencyclidine 25 ng/mL Phencyclidine 25 ng/mL Amphetamine 250 ng/mL 500

  19. Drug Testing - Memo from Glenn S. Podonsky

    Office of Environmental Management (EM)

    EXEC-2007-013433 December 3,2007 MEMORANDUM FOR THOMAS P. D'AGOSTINO UNDER SECRETARY FOR NUCLEAR SECURITY C.H. ALBRIGHT, JR. UNDER SECRETARY OF ENERGY RAYMOND L. ORBACH UNDER SECRETARY FOR S-CE A FROM: SUBJECT: Drug Testing / As established in his memorandum dated September 14, 2007, the Secretary has determined that applicants for, and holders of, a Department of Energy (DOE) Q or L access authorization (security clearance) will be in Testing Designated Positions (TDP) as specified in DOE Order

  20. On the separability of the extended molecule: Constructing the best localized molecular orbitals for an organic molecule bridging two model electrodes

    SciTech Connect (OSTI)

    Moreira, Rodrigo A.; Melo, Celso P. de

    2014-09-28

    Based on a quantum chemical valence formalism that allows the rigorous construction of best-localized molecular orbitals on specific parts of an extended system, we examined the separability of individual components of model systems relevant to the description of electron transport in molecular devices. We started by examining how to construct the maximally localized electronic density at the tip of a realistic model of a gold electrode. By varying the number of gold atoms included in the local region where to project the total electronic density, we quantitatively assess how many molecular orbitals are entirely localized in that region. We then considered a 1,4-benzene-di-thiol molecule connected to two model gold electrodes and examined how to localize the electronic density of the total system in the extended molecule, a fractional entity comprising the organic molecule plus an increasing number of the closest metal atoms. We were able to identify in a rigorous manner the existence of three physically different electronic populations, each one corresponding to a distinct set of molecular orbitals. First, there are those entirely localized in the extended molecule, then there is a second group of those completely distributed in the gold atoms external to that region, and, finally, there are those delocalized over the entire system. This latter group can be associated to the shared electronic population between the extended molecule and the rest of the system. We suggest that the treatment here presented could be useful in the theoretical analysis of the electronic transport in nanodevices whenever the use of localized molecular states are required by the physics of the specific problem, such as in cases of weak coupling and super-exchange limits.

  1. In situ Formation of Highly Conducting Covalent Au-C Contacts for Single-Molecule Junctions

    SciTech Connect (OSTI)

    Cheng, Z.L.; Hybertsen, M.; Skouta, R.; Vazquez, H.; Widawsky, J.R.; Schneebeli, S.; Chen, W.; Breslow, R.; Venkataraman, L.

    2011-06-01

    Charge transport across metal-molecule interfaces has an important role in organic electronics. Typically, chemical link groups such as thiols or amines are used to bind organic molecules to metal electrodes in single-molecule circuits, with these groups controlling both the physical structure and the electronic coupling at the interface. Direct metal-carbon coupling has been shown through C60, benzene and {pi}-stacked benzene but ideally the carbon backbone of the molecule should be covalently bonded to the electrode without intervening link groups. Here, we demonstrate a method to create junctions with such contacts. Trimethyl tin (SnMe{sub 3})-terminated polymethylene chains are used to form single-molecule junctions with a break-junction technique. Gold atoms at the electrode displace the SnMe{sub 3} linkers, leading to the formation of direct Au-C bonded single-molecule junctions with a conductance that is {approx}100 times larger than analogous alkanes with most other terminations. The conductance of these Au-C bonded alkanes decreases exponentially with molecular length, with a decay constant of 0.97 per methylene, consistent with a non-resonant transport mechanism. Control experiments and ab initio calculations show that high conductances are achieved because a covalent Au-C sigma ({sigma}) bond is formed. This offers a new method for making reproducible and highly conducting metal-organic contacts.

  2. Porous materials with pre-designed single-molecule traps for CO2 selective adsorption

    SciTech Connect (OSTI)

    Li, JR; Yu, JM; Lu, WG; Sun, LB; Sculley, J; Balbuena, PB; Zhou, HC

    2013-02-26

    Despite tremendous efforts, precise control in the synthesis of porous materials with pre-designed pore properties for desired applications remains challenging. Newly emerged porous metal-organic materials, such as metal-organic polyhedra and metal-organic frameworks, are amenable to design and property tuning, enabling precise control of functionality by accurate design of structures at the molecular level. Here we propose and validate, both experimentally and computationally, a precisely designed cavity, termed a 'single-molecule trap', with the desired size and properties suitable for trapping target CO2 molecules. Such a single-molecule trap can strengthen CO2-host interactions without evoking chemical bonding, thus showing potential for CO2 capture. Molecular single-molecule traps in the form of metal-organic polyhedra are designed, synthesised and tested for selective adsorption of CO2 over N-2 and CH4, demonstrating the trapping effect. Building these pre-designed single-molecule traps into extended frameworks yields metal-organic frameworks with efficient mass transfer, whereas the CO2 selective adsorption nature of single-molecule traps is preserved.

  3. Mesoporous Silica Nanomaterials for Applications in Catalysis, Sensing, Drug Delivery and Gene Transfection

    SciTech Connect (OSTI)

    Daniela Rodica Radu

    2005-12-19

    The central theme of this dissertation is represented by the versatility of mesoporous silica nanomaterials in various applications such as catalysis and bio-applications, with main focus on biological applications of Mesoporous Silica Nanospheres (MSN). The metamorphosis that we impose to these materials from catalysis to sensing and to drug and gene delivery is detailed in this dissertation. First, we developed a synthetic method that can fine tune the amount of chemically accessible organic functional groups on the pores surface of MSN by exploiting electrostatic and size matching between the cationic alkylammonium head group of the cetyltrimethylammonium bromide (CTAB) surfactant and various anionic organoalkoxysilane precursors at the micelle-water interface in a base-catalyzed condensation reaction of silicate. Aiming nature imitation, we demonstrated the catalytic abilities of the MSNs, We utilized an ethylenediamine functional group for chelating Cu{sup 2+} as a catalytic functional group anchored inside the mesopores. Thus, a polyalkynylene-based conducting polymer (molecular wire) was synthesized within the Cu-functionalized MSNs silica catalyst. For sensing applications, we have synthesized a poly(lactic acid) coated mesoporous silica nanosphere (PLA-MSN) material that serves as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. We exploited the mesoporosity of MSNs for encapsulating pharmaceutical drugs. We examined bio-friendly capping molecules such as polyamidoamine dendrimers of generations G2 to G4, to prevent the drug leaching. Next, the drug delivery system employed MSNs loaded with Doxorubicin, an anticancer drug. The results demonstrated that these nano-Trojan horses have ability to deliver Doxorubicin to cancer cells and induce their death. Finally, to demonstrate the potential of MSN as an universal cellular transmembrane nanovehicle, we anchored positively charged dendrimers on the surface of MSN and utilize them to complex cationic DNA. The p-EGFP-CI gene-coated MSN nanocomposite was able to transfect cancer cell lines, such as human HeLa and CHO cancer cell lines. The gene carrier ability of MSNs was further proved by transfecting primary cells and cotransfecting of two different genes in cancer cell lines. In sum, MSN are versatile partners in several types of applications.

  4. A nonplanar porphyrin-based receptor molecule for chiral amine ligands

    SciTech Connect (OSTI)

    MUZZI,CINZIA M.; MEDFORTH,CRAIG J.; SMITH,KEVIN M.; JIA,SONG-LING; SHELNUTT,JOHN A.

    2000-03-06

    A novel porphyrin-based receptor molecule for chiral amine ligands is described in which nonplanarity of the porphyrin macrocycle is used to orient the ligand and to enhance porphyrin-ligand interactions. The porphyrin macrocycle provides a versatile platform upon which to build elaborate superstructures, and this feature coupled with a rich and well-developed synthetic chemistry has led to the synthesis of many elegant models of heme protein active sites and numerous porphyrin-based receptor molecules. One design feature which is not usually considered in the design of porphyrin-based receptor molecules is nonplanarity of the porphyrin ring, although there are a few systems such as the pyridine sensitive Venus Flytrap and the chirality-memory molecule which illustrate that nonplanar porphyrin-based receptors can display unique and interesting behavior. Given the novel properties of these receptors and the continuing interest in the effects of nonplanarity on the properties of porphyrins the authors decided to investigate in more detail the potential applications of nonplanarity in the design of porphyrin-based receptors. Herein, they describe the design, synthesis, and characterization of a new kind of nonplanar porphyrin-based receptor molecule for chiral amines.

  5. Controlling orbital-selective Kondo effects in a single molecule through coordination chemistry

    SciTech Connect (OSTI)

    Tsukahara, Noriyuki; Kawai, Maki; Takagi, Noriaki; Minamitani, Emi; Kim, Yousoo

    2014-08-07

    Iron(II) phthalocyanine (FePc) molecule causes novel Kondo effects derived from the unique electronic structure of multi-spins and multi-orbitals when attached to Au(111). Two unpaired electrons in the d{sub z}{sup 2} and the degenerate d? orbitals are screened stepwise, resulting in spin and spin+orbital Kondo effects, respectively. We investigated the impact on the Kondo effects of the coordination of CO and NO molecules to the Fe{sup 2+} ion as chemical stimuli by using scanning tunneling microscopy (STM) and density functional theory calculations. The impacts of the two diatomic molecules are different from each other as a result of the different electronic configurations. The coordination of CO converts the spin state from triplet to singlet, and then the Kondo effects completely disappear. In contrast, an unpaired electron survives in the molecular orbital composed of Fe d{sub z}{sup 2} and NO 5? and 2?* orbitals for the coordination of NO, causing a sharp Kondo resonance. The isotropic magnetic response of the peak indicates the origin is the spin Kondo effect. The diatomic molecules attached to the Fe{sup 2+} ion were easily detached by applying a pulsed voltage at the STM junction. These results demonstrate that the single molecule chemistry enables us to switch and control the spin and the many-body quantum states reversibly.

  6. Formation of the diphenyl molecule in the crossed beam reaction of phenyl radicals with benzene

    SciTech Connect (OSTI)

    Zhang Fangtong; Gu Xibin; Kaiser, Ralf I.

    2008-02-28

    The chemical dynamics to form the D5-diphenyl molecule, C{sub 6}H{sub 5}C{sub 6}D{sub 5}, via the neutral-neutral reaction of phenyl radicals (C{sub 6}H{sub 5}) with D6-benzene (C{sub 6}D{sub 6}), was investigated in a crossed molecular beams experiment at a collision energy of 185 kJ mol{sup -1}. The laboratory angular distribution and time-of-flight spectra of the C{sub 6}H{sub 5}C{sub 6}D{sub 5} product were recorded at mass to charge m/z of 159. Forward-convolution fitting of our data reveals that the reaction dynamics are governed by an initial addition of the phenyl radical to the {pi} electron density of the D6-benzene molecule yielding a short-lived C{sub 6}H{sub 5}C{sub 6}D{sub 6} collision complex. The latter undergoes atomic deuterium elimination via a tight exit transition state located about 30 kJ mol{sup -1} above the separated reactants; the overall reaction to form D5-diphenyl from phenyl and D6-benzene was found to be weakly exoergic. The explicit identification of the D5-biphenyl molecules suggests that in high temperature combustion flames, a diphenyl molecule can be formed via a single collision event between a phenyl radical and a benzene molecule.

  7. Calculations on Isotope Separation by Laser Induced Photodissociation of Polyatomic Molecules. Final Report

    DOE R&D Accomplishments [OSTI]

    Lamb, W. E. Jr.

    1978-11-01

    This report describes research on the theory of isotope separation produced by the illumination of polyatomic molecules by intense infrared laser radiation. Newton`s equations of motion were integrated for the atoms of the SF{sub 6} molecule including the laser field interaction. The first year`s work has been largely dedicated to obtaining a suitable interatomic potential valid for arbitrary configurations of the seven particles. This potential gives the correct symmetry of the molecule, the equilibrium configuration, the frequencies of the six distinct normal modes of oscillation and the correct (or assumed) value of the total potential energy of the molecule. Other conditions can easily be imposed in order to obtain a more refined potential energy function, for example, by making allowance for anharmonicity data. A suitable expression was also obtained for the interaction energy between a laser field and the polyatomic molecule. The electromagnetic field is treated classically, and it would be easily possible to treat the cases of time dependent pulses, frequency modulation and noise.

  8. Takeda Advances Diabetes Drug Development at the ALS

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Takeda Advances Diabetes Drug Development at the ALS Takeda Advances Diabetes Drug Development at the ALS Print Tuesday, 19 May 2015 12:25 Type 2 diabetes mellitus (T2DM), characterized by abnormally high blood glucose levels, affects hundreds of millions of people worldwide. In the pursuit to better treat this disease, the human receptor protein GPR40 has been identified by pharmaceutical company Takeda as a potential new drug target. To this end, TAK-875 (fasiglifam), a partial agonist of

  9. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  10. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  11. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  12. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell growth. Protein kinases have in general been the target of many cancer drug designs, since

  13. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print Tuesday, 23 June 2015 13:00 The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal, healthy cells. It has been widely used to fight colon cancers and chronic myeloid leukemia. The protein kinase Abl is involved in regulating cell

  14. Food and Drug Administration White Oak Campus Environmental Stewardship and

    Office of Environmental Management (EM)

    Cost Savings | Department of Energy Food and Drug Administration White Oak Campus Environmental Stewardship and Cost Savings Food and Drug Administration White Oak Campus Environmental Stewardship and Cost Savings FEMP ESPC Success Story on water conservation and green energy at the Food and Drug Administration (FDA) White Oak Campus. PDF icon espc_ss_whiteoak.pdf More Documents & Publications Energy Savings Performance Contract Success Stories Harold Washington Social Security

  15. Takeda Advances Diabetes Drug Development at the ALS

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Takeda Advances Diabetes Drug Development at the ALS Print Type 2 diabetes mellitus (T2DM), characterized by abnormally high blood glucose levels, affects hundreds of millions of...

  16. In silico modeling to predict drug-induced phospholipidosis

    SciTech Connect (OSTI)

    Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G. Sadrieh, Nakissa

    2013-06-01

    Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure–activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80–81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ? 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. - Highlights: • New in silico models for predicting drug-induced phospholipidosis (DIPL) are described. • The training set data in the models is derived from the FDA's phospholipidosis database. • We find excellent predictivity values of the models based on external validation. • The models can support drug screening and regulatory decision-making on DIPL.

  17. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein...

  18. Food and Drug Administration White Oak Campus Environmental Stewardshi...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Oak Campus Environmental Stewardship and Cost Savings FEMP ESPC Success Story on water conservation and green energy at the Food and Drug Administration (FDA) White Oak Campus....

  19. Theoretical Treatment of the Thermophysical Properties of Fluids Containing Chain-like Molecules

    SciTech Connect (OSTI)

    Carol K. Hall

    2008-11-14

    This research program was designed to enhance our understanding of the behavior of fluids and fluid mixtures containing chain-like molecules. The original objective was to explain and predict the experimentally observed thermophysical properties, including phase equilibria and dynamics, of systems containing long flexible molecules ranging in length from alkanes to polymers. Over the years the objectives were expanded to include the treatment of molecules that were not chain-like. Molecular dynamics and Monte Carlo computer simulations were used to investigate how variations in molecular size, shape and architecture influence the types of phase equilibria, thermodynamic properties, structure and surface interactions that are observed experimentally. The molecular insights and theories resulting from this program could eventually serve as the foundation upon which to build correlations of the properties of fluids that are both directly and indirectly related to the Nation’s energy resources including: petroleum, natural gas, and polymer solutions, melts, blends, and materials.

  20. Single molecule detection using charge-coupled device array technology. Technical progress report

    SciTech Connect (OSTI)

    Denton, M.B.

    1992-07-29

    A technique for the detection of single fluorescent chromophores in a flowing stream is under development. This capability is an integral facet of a rapid DNA sequencing scheme currently being developed by Los Alamos National Laboratory. In previous investigations, the detection sensitivity was limited by the background Raman emission from the water solvent. A detection scheme based on a novel mode of operating a Charge-Coupled Device (CCD) is being developed which should greatly enhance the discrimination between fluorescence from a single molecule and the background Raman scattering from the solvent. Register shifts between rows in the CCD are synchronized with the sample flow velocity so that fluorescence from a single molecule is collected in a single moving charge packet occupying an area approaching that of a single pixel while the background is spread evenly among a large number of pixels. Feasibility calculations indicate that single molecule detection should be achieved with an excellent signal-to-noise ratio.

  1. Elastic Cross Sections for Electron Collisions with Molecules Relevant to Plasma Processing

    SciTech Connect (OSTI)

    Yoon, J.-S.; Song, M.-Y.; Kato, H.; Hoshino, M.; Tanaka, H.; Brunger, M. J.; Buckman, S. J.; Cho, H.

    2010-09-15

    Absolute electron-impact cross sections for molecular targets, including their radicals, are important in developing plasma reactors and testing various plasma processing gases. Low-energy electron collision data for these gases are sparse and only the limited cross section data are available. In this report, elastic cross sections for electron-polyatomic molecule collisions are compiled and reviewed for 17 molecules relevant to plasma processing. Elastic cross sections are essential for the absolute scale conversion of inelastic cross sections, as well as for testing computational methods. Data are collected and reviewed for elastic differential, integral, and momentum transfer cross sections and, for each molecule, the recommended values of the cross section are presented. The literature has been surveyed through early 2010.

  2. Electrochemical assembly of organic molecules by the reduction of iodonium salts

    DOE Patents [OSTI]

    Dirk, Shawn M. (Albuquerque, NM); Howell, Stephen W. (Albuquerque, NM); Wheeler, David R. (Albuquerque, NM)

    2009-06-23

    Methods are described for the electrochemical assembly of organic molecules on silicon, or other conducting or semiconducting substrates, using iodonium salt precursors. Iodonium molecules do not assemble on conducting surfaces without a negative bias. Accordingly, the iodonium salts are preferred for patterning applications that rely on direct writing with negative bias. The stability of the iodonium molecule to acidic conditions allows them to be used with standard silicon processing. As a directed assembly process, the use of iodonium salts provides for small features while maintaining the ability to work on a surface and create structures on a wafer level. Therefore, the process is amenable for mass production. Furthermore, the assembled monolayer (or multilayer) is chemically robust, allowing for subsequent chemical manipulations and the introduction of various molecular functionalities for various chemical and biological applications.

  3. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    SciTech Connect (OSTI)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-03-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  4. Hadronic physics of q anti q light quark mesons, quark molecules and glueballs

    SciTech Connect (OSTI)

    Lindenbaum, S.J.

    1980-10-01

    A brief introduction reviews the development of QCD and defines quark molecules and glueballs. This review is concerned primarily with u, d, and s quarks, which provide practically all of the cross section connected with hadronic interactions. The following topics form the bulk of the paper: status of quark model classification for conventional u, d, s quark meson states; status of multiquark or quark molecule state predictions and experiments; glueballs and how to find them; and the OZI rule in decay and production and how glueballs might affect it. 17 figures, 1 table. (RWR)

  5. Proposed Molecular Beam Determination of Energy Partition in the Photodissociation of Polyatomic Molecules

    DOE R&D Accomplishments [OSTI]

    Zare, P. N.; Herschbach, D. R.

    1964-01-29

    Conventional photochemical experiments give no information about the partitioning of energy between translational recoil and internal excitation of the fragment molecules formed in photodissociation of a polyatomic molecule. In a molecular beam experiment, it becomes possible to determine the energy partition from the form of the laboratory angular distribution of one of the photodissociation products. A general kinematic analysis is worked out in detail, and the uncertainty introduced by the finite angular resolution of the apparatus and the velocity spread in the parent beam is examined. The experimental requirements are evaluated for he photolysis of methyl iodide by the 2537 angstrom Hg line.

  6. Spintronic transport of a non-magnetic molecule between magnetic electrodes

    SciTech Connect (OSTI)

    Kondo, Hisashi; Ohno, Takahisa; Institute of Industrial Science, University of Tokyo, Meguro, Tokyo 153-8505

    2013-12-02

    The spintronic transport properties of a junction system composed of a non-magnetic molecule sandwiched between ferromagnetic metal electrodes are investigated theoretically using a non-equilibrium Green's function method based on density functional theory. It is revealed that in such a system, the molecular magnetic properties induced by hybridization with the magnetic electrodes play a crucial role. Alignment of the induced molecular spin-split levels is strongly related to the spin injection and tunneling magneto-resistance effects. It is found that in the system with weaker molecule-electrode interaction, stronger spintronic effects of the spin injection and tunneling magneto-resistance are observed.

  7. Electromagnetic wave propagation in a random distribution of C{sub 60} molecules

    SciTech Connect (OSTI)

    Moradi, Afshin

    2014-10-15

    Propagation of electromagnetic waves in a random distribution of C{sub 60} molecules are investigated, within the framework of the classical electrodynamics. Electronic excitations over the each C{sub 60} molecule surface are modeled by a spherical layer of electron gas represented by two interacting fluids, which takes into account the different nature of the ? and ? electrons. It is found that the present medium supports four modes of electromagnetic waves, where they can be divided into two groups: one group with shorter wavelength than the light waves of the same frequency and the other with longer wavelength than the free-space radiation.

  8. Photoinduced nucleation: a novel tool for detecting molecules in air at ultra-low concentrations

    DOE Patents [OSTI]

    Katz, Joseph L. (Baltimore, MD); Lihavainen, Heikki (Masala, FI); Rudek, Markus M. (Bruchkoebel, DE); Salter, Brian C. (New Market, MD)

    2002-01-01

    A method and apparatus for determining the presence of molecules in a gas at concentrations of less than about 100 ppb. Light having wavelengths in the range from about 200 nm to about 350 nm is used to illuminate a flowing sample of the gas causing the molecules if present to form clusters. A mixture of the illuminated gas and a vapor is cooled until the vapor is supersaturated so that there is a small rate of homogeneous nucleation. The supersaturated vapor condenses on the clusters thus causing the clusters to grow to a size sufficient to be counted by light scattering and then the clusters are counted.

  9. Measurement of the nuclear polarization of hydrogen and deuterium molecules using a Lamb-shift polarimeter

    SciTech Connect (OSTI)

    Engels, Ralf Gorski, Robert; Grigoryev, Kiril; Mikirtychyants, Maxim; Rathmann, Frank; Seyfarth, Hellmut; Ströher, Hans; Weiss, Philipp; Kochenda, Leonid; Kravtsov, Peter; Trofimov, Viktor; Tschernov, Nikolay; Vasilyev, Alexander; Vznuzdaev, Marat; Schieck, Hans Paetz gen.

    2014-10-15

    Lamb-shift polarimeters are used to measure the nuclear polarization of protons and deuterons at energies of a few keV. In combination with an ionizer, the polarization of hydrogen and deuterium atoms was determined after taking into account the loss of polarization during the ionization process. The present work shows that the nuclear polarization of hydrogen or deuterium molecules can be measured as well, by ionizing the molecules and injecting the H{sub 2}{sup +} (or D{sub 2}{sup +}) ions into the Lamb-shift polarimeter.

  10. Lab Breakthrough: X-ray Laser Captures Atoms and Molecules in Action |

    Office of Environmental Management (EM)

    Department of Energy X-ray Laser Captures Atoms and Molecules in Action Lab Breakthrough: X-ray Laser Captures Atoms and Molecules in Action July 18, 2012 - 12:51pm Addthis The Linac Coherent Light Source at SLAC is the world's most powerful X-ray laser, which helps researchers understand the extreme conditions found in the hearts of stars and giant planets guiding research into nuclear fusion, the mechanism that powers the sun. View the entire Lab Breakthrough playlist. Michael Hess Michael

  11. The two polymorphs of N-DNAT, a high nitrogen molecule

    SciTech Connect (OSTI)

    Lee, K.Y.; Chan, M.

    1995-09-01

    A novel azo triazole molecule was prepared. Based on X-ray crystallography data, this molecule, 1,1{prime}-dinitro-3,3{prime}-azo-1,2,4-triazole (N-DNAT) exists in two forms. The yellow color polymorph has a crystal density of 1.701 g/cm{sup 3}, while the density of the orange crystal is 1.831 g/cm{sup 3}. Data from specific impulse (Isp) calculation indicates that N-DNAT is a potential candidate for propellant applications.

  12. Drug-Free Federal Workplace Testing Implementation Program

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2012-12-06

    The subject directive provides requirements and responsibilities for the implementation of a workplace program to test for the use of illegal drugs to facilitate the maintenance of a drug-free Federal workplace. In the course of the revision, the document number will change from DOE O 3792.3 to DOE O 343.1.

  13. Light Sources Help Discover New Drug Against Melanoma

    Broader source: Energy.gov [DOE]

    A new drug designed to fight melanoma was discovered thanks to the powerful x-ray facilities at our national labs. The x-rays helped determine the precise structure of a mutated protein involved in this cancer –- and potential drug candidates that could stop its spread.

  14. Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery

    SciTech Connect (OSTI)

    Li, Dongdong; Zhu, Yuntao; Liang, Zhiqiang

    2013-06-01

    Highlights: ? The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ? The materials have high surface area and amino group. ? The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N{sub 2} adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH{sub 3}{sup +} on the matrix and -COO{sup ?}belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate.

  15. Drug interactions evaluation: An integrated part of risk assessment of therapeutics

    SciTech Connect (OSTI)

    Zhang, Lei; Reynolds, Kellie S.; Zhao, Ping; Huang, Shiew-Mei

    2010-03-01

    Pharmacokinetic drug interactions can lead to serious adverse events or decreased drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug interaction potential is an integral part of risk assessment during drug development and regulatory review. Alteration of activities of enzymes or transporters involved in the absorption, distribution, metabolism, or excretion of a new molecular entity by concomitant drugs may alter drug exposure, which can impact response (safety or efficacy). The recent Food and Drug Administration (FDA) draft drug interaction guidance ( (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072101.pdf)) highlights the methodologies and criteria that may be used to guide drug interaction evaluation by industry and regulatory agencies and to construct informative labeling for health practitioner and patients. In addition, the Food and Drug Administration established a 'Drug Development and Drug Interactions' website to provide up-to-date information regarding evaluation of drug interactions ( (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm)). This review summarizes key elements in the FDA drug interaction guidance and new scientific developments that can guide the evaluation of drug-drug interactions during the drug development process.

  16. Calculation of resonances in a dt{mu} molecule by the R-matrix method

    SciTech Connect (OSTI)

    Mil'nikov, Gennady V.; Nakamura, Hiroki

    2003-03-01

    Using the spectral representation of Green's function, we calculate the density of states and extract parameters of resonances in the scattering system. The method is implemented for the resonances in the dt{mu} molecule below the t{mu} (n=2) threshold.

  17. Practical Calculation of Molecular Acidity with the Aid of a Reference Molecule

    SciTech Connect (OSTI)

    Burger, Steven K; Liu, Shubin; Ayers, Paul W

    2011-02-24

    A set of linear free energy models are presented for determining the pK{sub a} values of amines, alcohols, and carboxylic acids. Models are determined from a series of pK{sub a} predictors, taken both from traditional natural atomic orbital analysis (NAO) and from a novel approach introduced here of using a reference molecule: an ammonium ion for amines and a hydrogen sulfide molecule for alcohols and carboxylic acids. Using these reference molecules, we calculate the barrier to proton transfer and show that a number of properties associated with the transition state are correlated with the pK{sub a}. By considering 38 predictors, we obtain a four-variable model for amines and a three-variable model for oxygen-containing compounds. The model for amines is based on 145 compounds and has a root mean squared error (RMSE) of 0.45 and R{sup 2} = 0.98. The oxygen set has 48 molecules: RMSE = 0.26, and R{sup 2} = 0.993. Similar, linear, and multilinear models are constructed after separating the sets into chemically similar categories: alcohols, carboxylic acids, and primary, secondary, tertiary, and aromatic amines. This separation gives simpler models with relatively low RMSE values, where the most important predictor of the pK{sub a} is the difference in energy between transferring the proton from the reference molecular base to the conjugate acid from the data set.

  18. The adsorption properties of CO molecules on single-layer graphene nanoribbons

    SciTech Connect (OSTI)

    Yi, Chenglong; Wang, Weidong, E-mail: wangwd@mail.xidian.edu.cn; Shen, Cuili [School of Electrical and Mechanical Engineering, Xidian University, Xi'an 710071 (China)] [School of Electrical and Mechanical Engineering, Xidian University, Xi'an 710071 (China)

    2014-03-15

    The adsorption properties of CO molecules on graphene nanoribbons (GRNs) are studied through the molecular dynamics (MD) method. The AIREBO and LJ potentials are used to describe the C-C bonds in GNR and the interactions between the carbon atoms in GNR and CO molecules, respectively. The influences of the environmental pressure and charge density on the adsorption properties of CO molecules on GRNs are taken into account in this study. The effects of charges carried by GNRs on the adsorption properties are investigated in two aspects: atom distribution and energy evolution. Its observation from the results shows that the Coulomb force plays a more important role in the adsorption phenomenon than the van der Waals force, and the higher the charge density is, the larger the amount of the adsorbed CO molecules becomes. Low charge densities (<3.291 C/m{sup 2}) do little for the system, that is to say, the GNRs present similar properties to the ones with no charges. However, relatively high charge densities (>4.937 C/m{sup 2}) have an obvious effect on the whole system. The results also indicate that the environmental pressure has great influence on the adsorption properties of COs on GRN, and the higher the pressure is, the greater the adsorption energy becomes.

  19. Frontiers in Laser Cooling, Single-Molecule Biophysics, and Enrgy Science: A Talk by Carl Wieman

    ScienceCinema (OSTI)

    Wieman, Carl

    2011-04-13

    Carl Wieman presents a talk at Frontiers in Laser Cooling, Single-Molecule Biophysics and Energy Science, a scientific symposium honoring Steve Chu, director of Lawrence Berkeley National Laboratory and recipient of the 1997 Nobel Prize in Physics. The symposium was held August 30, 2008 in Berkeley.

  20. Tetrakis(1-imidazolyl) borate (BIM4) based zwitterionic and related molecules used as electron injection layers

    DOE Patents [OSTI]

    Li, Huaping; Xu, Yunhua; Bazan, Guillermo C

    2013-02-05

    Tetrakis(1-imidazolyl)borate (BIm4) based zwitterionic and/or related molecules for the fabrication of PLEDs is provided. Device performances with these materials approaches that of devices with Ba/Al cathodes for which the cathode contact is ohmic. Methods of producing such materials, and electron injection layers and devices containing these materials are also provided.

  1. Atomic Force Microscopy Studies of Lipophosphoglycan (LPG) Molecules in Lipid Bilayers

    SciTech Connect (OSTI)

    LAST, JULIE A.; HUBER, TINA; SASAKI, DARRYL Y.; SALVATORE, BRIAN; TURCO, SALVATORE J.

    2003-03-01

    Lipophosphoglycan (LPG) is a lypopolysaccharide found on the surface of the parasite Leishmania donovani that is thought to play an essential role in the infection of humans with leishamniasis. LPG acts as an adhesion point for the parasite to the gut of the sand fly, whose bite is responsible for transmitting the disease. In addition, LPG acts to inhibit protein kinase C (PKC) in the human macrophage, possibly by structural changes in the membrane. The Ca{sup 2+} ion is believed to play a role in the infection cycle, acting both as a crosslinker between LPG molecules and by playing a part in modulating PKC activity. To gain insight into the structure of LPG within a supported lipid membrane and into the structural changes that occur due to Ca{sup 2+} ions, we have employed the atomic force microscope (AFM). We have observed that the LPG molecules inhibit bilayer fusion, resulting in bilayer islands on the mica surface. One experiment suggests that the LPG molecules are parallel to the mica surface and that the structure of the LPG changes upon addition of Ca{sup 2+}, with an increase in the height of the LPG molecules from the bilayer surface and an almost complete coverage of LPG on the bilayer island.

  2. Ultraviolet light absorbers having two different chromophors in the same molecule

    DOE Patents [OSTI]

    Vogl, Otto (Brooklyn, NY); Li, Shanjun (Brooklyn, NY)

    1988-05-17

    Ultraviolet light absorbing compounds having two different chromophors in the same molecule, particularly the benzotriazole chromophor and either the dihydroxybenzophenone or dihydroxyacetophenone chromophor; specifically, the two compounds 3,5-[di(2H-benzotriazole-2-yl)]-2,4-dihydroxyacetophenone and 3,5-[di(2H-benzotriazole-2-yl)]2,4-dihydroxybenzophenone.

  3. Guest Molecule Exchange Kinetics for the 2012 Ignik Sikumi Gas Hydrate Field Trial

    SciTech Connect (OSTI)

    White, Mark D.; Lee, Won Suk

    2014-05-14

    A commercially viable technology for producing methane from natural gas hydrate reservoirs remains elusive. Short-term depressurization field tests have demonstrated the potential for producing natural gas via dissociation of the clathrate structure, but the long-term performance of the depressurization technology ultimately requires a heat source to sustain the dissociation. A decade of laboratory experiments and theoretical studies have demonstrated the exchange of pure CO2 and N2-CO2 mixtures with CH4 in sI gas hydrates, yielding critical information about molecular mechanisms, recoveries, and exchange kinetics. Findings indicated the potential for producing natural gas with little to no production of water and rapid exchange kinetics, generating sufficient interest in the guest-molecule exchange technology for a field test. In 2012 the U.S. DOE/NETL, ConocoPhillips Company, and Japan Oil, Gas and Metals National Corporation jointly sponsored the first field trial of injecting a mixture of N2-CO2 into a CH4-hydrate bearing formation beneath the permafrost on the Alaska North Slope. Known as the Ignik Sikumi #1 Gas Hydrate Field Trial, this experiment involved three stages: 1) the injection of a N2-CO2 mixture into a targeted hydrate-bearing layer, 2) a 4-day pressurized soaking period, and 3) a sustained depressurization and fluid production period. Data collected during the three stages of the field trial were made available after an extensive quality check. These data included continuous temperature and pressure logs, injected and recovered fluid compositions and volumes. The Ignik Sikumi #1 data set is extensive, but contains no direct evidence of the guest-molecule exchange process. This investigation is directed at using numerical simulation to provide an interpretation of the collected data. A numerical simulator, STOMP-HYDT-KE, was recently completed that solves conservation equations for energy, water, mobile fluid guest molecules, and hydrate guest molecules, for up to three gas hydrate guest molecules: CH4, CO2, and N2. The independent tracking of mobile fluid and hydrate guest molecules allows for the kinetic exchange of guest molecules between the mobile fluids and hydrate. The particular interest of this numerical investigation is to determine whether kinetic exchange parameters, determined from laboratory-scale experiments, are directly applicable to interpreting the Ignik Sikumi #1 data.

  4. Shear-stress-induced structural arrangement of water molecules in nanoscale Couette flow with slipping at wall boundary

    SciTech Connect (OSTI)

    Lin, Jau-Wen

    2014-08-07

    This study investigated the structuring of water molecules in a nanoscale Couette flow with the upper plate subjected to lateral forces with various magnitudes and water slipping against a metal wall. It was found that when the upper plate is subjected to a force, the water body deforms into a parallelepiped. Water molecules in the channel are then gradually arranged into lattice positions, creating a layered structure. The structural arrangement of water molecules is caused by the water molecules accommodating themselves to the increase in energy under the application of a lateral force on the moving plate. The ordering arrangement of water molecules increases the rotational degree of freedom, allowing the molecules to increase their Coulomb potential energy through polar rotation that accounts for the energy input through the upper plate. With a force continuously applied to the upper plate, the water molecules in contact with the upper plate move forward until slip between the water and upper plate occurs. The relation between the structural arrangement of water molecules, slip at the wall, and the shear force is studied. The relation between the slip and the locking/unlocking of water molecules to metal atoms is also studied.

  5. A quantitative quantum-chemical analysis tool for the distribution of mechanical force in molecules

    SciTech Connect (OSTI)

    Stauch, Tim; Dreuw, Andreas

    2014-04-07

    The promising field of mechanochemistry suffers from a general lack of understanding of the distribution and propagation of force in a stretched molecule, which limits its applicability up to the present day. In this article, we introduce the JEDI (Judgement of Energy DIstribution) analysis, which is the first quantum chemical method that provides a quantitative understanding of the distribution of mechanical stress energy among all degrees of freedom in a molecule. The method is carried out on the basis of static or dynamic calculations under the influence of an external force and makes use of a Hessian matrix in redundant internal coordinates (bond lengths, bond angles, and dihedral angles), so that all relevant degrees of freedom of a molecule are included and mechanochemical processes can be interpreted in a chemically intuitive way. The JEDI method is characterized by its modest computational effort, with the calculation of the Hessian being the rate-determining step, and delivers, except for the harmonic approximation, exact ab initio results. We apply the JEDI analysis to several example molecules in both static quantum chemical calculations and Born-Oppenheimer Molecular Dynamics simulations in which molecules are subject to an external force, thus studying not only the distribution and the propagation of strain in mechanically deformed systems, but also gaining valuable insights into the mechanochemically induced isomerization of trans-3,4-dimethylcyclobutene to trans,trans-2,4-hexadiene. The JEDI analysis can potentially be used in the discussion of sonochemical reactions, molecular motors, mechanophores, and photoswitches as well as in the development of molecular force probes.

  6. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print Wednesday, 27 February 2008 00:00 The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II

  7. Method and apparatus for enhanced sequencing of complex molecules using surface-induced dissociation in conjunction with mass spectrometric analysis

    DOE Patents [OSTI]

    Laskin, Julia [Richland, WA; Futrell, Jean H [Richland, WA

    2008-04-29

    The invention relates to a method and apparatus for enhanced sequencing of complex molecules using surface-induced dissociation (SID) in conjunction with mass spectrometric analysis. Results demonstrate formation of a wide distribution of structure-specific fragments having wide sequence coverage useful for sequencing and identifying the complex molecules.

  8. Takeda Advances Diabetes Drug Development at the ALS

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Advances Diabetes Drug Development at the ALS Print Tuesday, 19 May 2015 12:25 Type 2 diabetes mellitus (T2DM), characterized by abnormally high blood glucose levels, affects...

  9. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    a cell's DNA is fatal to the cell, which is why drugs that target topo II serve as agents against bacterial infections and some forms of cancer. This first ever structural...

  10. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and...

  11. The different adsorption mechanism of methane molecule onto a boron nitride and a graphene flakes

    SciTech Connect (OSTI)

    Seyed-Talebi, Seyedeh Mozhgan; Neek-Amal, M.

    2014-10-21

    Graphene and single layer hexagonal boron-nitride are two newly discovered 2D materials with wonderful physical properties. Using density functional theory, we study the adsorption mechanism of a methane molecule over a hexagonal flake of single layer hexagonal boron-nitride (h-BN) and compare the results with those of graphene. We found that independent of the used functional in our ab-initio calculations, the adsorption energy in the h-BN flake is larger than that for graphene. Despite of the adsorption energy profile of methane over a graphene flake, we show that there is a long range behavior beyond minimum energy in the adsorption energy of methane over h-BN flake. This result reveals the higher sensitivity of h-BN sheet to the adsorption of a typical closed shell molecule with respect to graphene. The latter gives insight in the recent experiments of graphene over hexagonal boron nitride.

  12. High-throughput, dual probe biological assays based on single molecule detection

    DOE Patents [OSTI]

    Hollars, Christopher W. (Brentwood, CA); Huser, Thomas R. (Livermore, CA); Lane, Stephen M. (Oakland, CA); Balhorn, Rodney L. (Livermore, CA); Bakajin, Olgica (San Leandro, CA); Darrow, Christopher (Pleasanton, CA); Satcher, Jr., Joe H. (Patterson, CA)

    2006-07-11

    A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 .mu.m.times.100 .mu.m.times.100 .mu.m. A device using these methods would have 10.sup.3 10.sup.4 greater throughput than previous one-dimensional (1D) micro-stream devices having 1 .mu.m.sup.3 interrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (.about.10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.

  13. Communication: Feshbach resonances in the water molecule revealed by state-selective spectroscopy

    SciTech Connect (OSTI)

    Grechko, Maxim; Maksyutenko, Pavlo; Rizzo, Thomas R.; Boyarkin, Oleg V.

    2010-08-28

    We employ triple-resonance vibrational overtone excitation to access quasibound states of water from several fully characterized bound states of the molecule. Comparison of the measured dissociation spectra allows a rigorous assignment of rotational quantum numbers J, nuclear spin and parity, and a tentative vibrational characterization of the observed resonances. Their asymmetrical shapes (Fano profiles) reflect interference of dipole moments for transitions to these resonances with that to the dissociative continuum. The assignments and Fano profile parameters of the resonances stand as a benchmark for the extension of accurate quantum-mechanical calculations to activated complexes of water. The narrow widths of some of these resonances indicate that water molecules may survive for as long as up to 60 ps in states above the dissociation threshold. We consider the possible implication of such long-lived states for the kinetics of water dissociation and the OH+H association reaction.

  14. Rotational fluctuation of molecules in quantum clusters. I. Path integral hybrid Monte Carlo algorithm

    SciTech Connect (OSTI)

    Miura, Shinichi [Institute for Molecular Science, 38 Myodaiji, Okazaki 444-8585 (Japan)

    2007-03-21

    In this paper, we present a path integral hybrid Monte Carlo (PIHMC) method for rotating molecules in quantum fluids. This is an extension of our PIHMC for correlated Bose fluids [S. Miura and J. Tanaka, J. Chem. Phys. 120, 2160 (2004)] to handle the molecular rotation quantum mechanically. A novel technique referred to be an effective potential of quantum rotation is introduced to incorporate the rotational degree of freedom in the path integral molecular dynamics or hybrid Monte Carlo algorithm. For a permutation move to satisfy Bose statistics, we devise a multilevel Metropolis method combined with a configurational-bias technique for efficiently sampling the permutation and the associated atomic coordinates. Then, we have applied the PIHMC to a helium-4 cluster doped with a carbonyl sulfide molecule. The effects of the quantum rotation on the solvation structure and energetics were examined. Translational and rotational fluctuations of the dopant in the superfluid cluster were also analyzed.

  15. Interplay of radiative and nonradiative transitions in surface hopping with radiation-molecule interactions

    SciTech Connect (OSTI)

    Bajo, Juan José; Granucci, Giovanni Persico, Maurizio

    2014-01-28

    We implemented a method for the treatment of field induced transitions in trajectory surface hopping simulations, in the framework of the local diabatization scheme, especially suited for on-the-fly dynamics. The method is applied to a simple one-dimensional model with an avoided crossing and compared with quantum wavepacket dynamics. The results show the importance of introducing a proper decoherence correction to surface hopping, in order to obtain meaningful results. Also the energy conservation policy of standard surface hopping must be revised: in fact, the quantum wavepacket energetics is well reproduced if energy absorption/emission is allowed for in the hops determined by radiation-molecule coupling. To our knowledge, this is the first time the issues of decoherence and energy conservation have been analyzed in depth to devise a mixed quantum-classical method for dynamics with molecule-field interactions.

  16. Formation and incorporation of SiF{sub 4} molecules in F-implanted preamorphized Si

    SciTech Connect (OSTI)

    De Salvador, D.; Bisognin, G.; Napolitani, E.; Mastromatteo, M.; Baggio, N.; Carnera, A.; Boscherini, F.; Cristiano, F.

    2009-09-07

    The local structure of fluorine incorporated in crystalline silicon following solid phase epitaxial regrowth was investigated by means of x-ray absorption spectroscopy at the F K-edge. We clearly demonstrate that most F is found in SiF{sub 4} molecules in the crystalline matrix. A kinetic pathway, which explains our observation and which is also able to rationalize previous results in a common and coherent framework, is proposed.

  17. Ultraviolet light absorbers having two different chromophors in the same molecule

    DOE Patents [OSTI]

    Vogl, O.; Li, S.

    1983-10-06

    This invention relates to novel ultraviolet light absorbers having two chromophors in the same molecule, and more particularly to benzotriazole substituted dihydroxybenzophenones and acetophenones. More particularly, this invention relates to 3,5-(di(2H-benzotriazole-2-yl))-2,4-dihydroxybenzophenone and 3,5-(di(2H-benzotriazole-2-yl))-2,4-dihydroxyacetophenone which are particularly useful as an ultraviolet light absorbers.

  18. Nucleic acid molecules conferring enhanced ethanol tolerance and microorganisms having enhanced tolerance to ethanol

    DOE Patents [OSTI]

    Brown, Steven; Guss, Adam; Yang, Shihui; Karpinets, Tatiana; Lynd, Lee; Shao, Xiongjun

    2014-01-14

    The present invention provides isolated nucleic acid molecules which encode a mutant acetaldehyde-CoA/alcohol dehydrogenase or mutant alcohol dehydrogenase and confer enhanced tolerance to ethanol. The invention also provides related expression vectors, genetically engineered microorganisms having enhanced tolerance to ethanol, as well as methods of making and using such genetically modified microorganisms for production of biofuels based on fermentation of biomass materials.

  19. Viable Single-Molecule Diodes | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Viable Single-Molecule Diodes Advanced Scientific Computing Research (ASCR) ASCR Home About Research Facilities Science Highlights Benefits of ASCR Funding Opportunities Advanced Scientific Computing Advisory Committee (ASCAC) Community Resources Contact Information Advanced Scientific Computing Research U.S. Department of Energy SC-21/Germantown Building 1000 Independence Ave., SW Washington, DC 20585 P: (301) 903-7486 F: (301) 903-4846 E: Email Us More Information » 11.01.15 Viable

  20. Small Molecule Adsorption in Open-Site Metal-Organic Frameworks: A

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Systematic Density Functional Theory Study for Rational Design | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Small Molecule Adsorption in Open-Site Metal-Organic Frameworks: A Systematic Density Functional Theory Study for Rational Design Previous Next List Kyuho Lee, Joshua D. Howe, Li-Chiang Lin, Berend Smit, and Jeffrey B. Neaton, Chem. Mater. 27, 668-678 (2015) DOI: 10.1021/cm502760q Abstract: Using density functional theory, we systematically

  1. Subtask 1: Molecules, Materials, and Systems for Solar Fuels | ANSER Center

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    | Argonne-Northwestern National Laboratory 1: Molecules, Materials, and Systems for Solar Fuels Home > Research > Subtask 1 The above figure depicts an iridium catalyst used for water splitting. The above figure depicts an iridium catalyst used for water splitting. The greatest challenge facing the development of solar fuels is efficient fuel production at acceptable rates and driving forces. The ANSER Center is confronting this challenge by taking a hierarchical approach to designing,

  2. Mathematical modeling of the aptamers and its effect on small molecule

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    transport into the cell | The Ames Laboratory Mathematical modeling of the aptamers and its effect on small molecule transport into the cell In this proposed research, we expect to explore the hypothesis that the levels of accumulation of chemicals by cells can be mediated by mobile intracellular receptors1. As initial evidence of this hypothesis, we have recently determined experimentally that bacterial uptake of a toxin can be increased by aptamer receptors expressed by the cells. We

  3. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during

  4. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during

  5. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during

  6. Molecular conformations, interactions, and properties associated with drug

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    efficiency and clinical performance among VEGFR TK inhibitors Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors Print Monday, 17 September 2012 00:00 Pictured are crystals that contain VEGFR2 tyrosine kinase in complex with an inhibitor from a class of potent anticancer

  7. Takeda Advances Diabetes Drug Development at the ALS

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Takeda Advances Diabetes Drug Development at the ALS Print Type 2 diabetes mellitus (T2DM), characterized by abnormally high blood glucose levels, affects hundreds of millions of people worldwide. In the pursuit to better treat this disease, the human receptor protein GPR40 has been identified by pharmaceutical company Takeda as a potential new drug target. To this end, TAK-875 (fasiglifam), a partial agonist of GPR40, was brought into clinical development by Takeda as a possible new treatment

  8. Topo II: An Enzyme Target for Antibacterial and Cancer Drugs

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Topo II: An Enzyme Target for Antibacterial and Cancer Drugs Print The veil has finally been lifted on an enzyme that is critical to the process of DNA transcription and replication and is a prime target of antibacterial and anticancer drugs. Researchers at Berkeley Lab and the University of California, Berkeley, have produced the first three-dimensional structural images of a DNA-bound type II topoisomerase (topo II) that is responsible for untangling coiled strands of the chromosome during

  9. Implementation Guidance, Drug Testing - December 3, 2007 | Department of

    Energy Savers [EERE]

    Energy Implementation Guidance, Drug Testing - December 3, 2007 Implementation Guidance, Drug Testing - December 3, 2007 December 3, 2007 Implementation guidance for applicants for, and holders of, a Department of Energy (DOE) Q or L access authorization (security clearance) selected for Testing Designated Positions (TDP) As established in his memorandum dated September 14, 2007, the Secretary has determined that applicants for, and holders of, a Department of Energy (DOE) Q or L access

  10. DOE Laboratories Help Develop Promising New Cancer Fighting Drug,

    Energy Savers [EERE]

    Vemurafenib | Department of Energy Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib DOE Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib August 18, 2011 - 1:03pm Addthis Powerful X-Rays Enable Development of Successful Treatment for Melanoma and Other Life-Threatening Diseases WASHINGTON, DC - Powerful X-ray technology developed at the U.S. Department of Energy's (DOE's) national laboratories is revealing new insights into diseases ranging

  11. Flow cytometry aids basic cell biology research and drug discovery

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Flow cytometry aids basic cell biology research and drug discovery Flow cytometry aids basic cell biology research and drug discovery Life Technologies Corporation and LANL have released the Attune® Acoustic Focusing Cytometer, featuring a reduced footprint, reduced consumables, and an affordable price. April 3, 2012 Attune® Acoustic Focusing Cytometer The Attune® Acoustic Focusing Cytometer achieves sample throughput at rates over 10 times faster than other cytometers-up to 1,000 μL per

  12. Computer modeling reveals how surprisingly potent hepatitis C drug works

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Hepatitis C computer modeling Computer modeling reveals how surprisingly potent hepatitis C drug works A study reveals how daclatasvir targets one of its proteins and causes the fastest viral decline ever seen with anti-HCV drugs - within 12 hours of treatment. February 19, 2013 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy

  13. FACT SHEET ON THE CONSEQUENCES OF A FAILED DRUG TEST

    Office of Environmental Management (EM)

    FACT SHEET ON THE CONSEQUENCES OF A POSITIVE DRUG TEST The Secretary has determined that applicants for, and holders of, a DOE "Q" or "L" access authorization (security clearance) will be in Testing Designated Positions (TDP) as specified in DOE Order 3792.3, Drug-Free Federal Workplace Testing Implementation Program, for federal employees, and Title 10 Code of Federal Regulations, Part 707, Workplace Substance Abuse Programs at DOE Sites, for contractor employees.

  14. Laser separation of nitrogen isotopes by the IR+UV dissociation of ammonia molecules

    SciTech Connect (OSTI)

    Apatin, V M; Klimin, S A; Laptev, V B; Lokhman, V N; Ogurok, D D; Pigul'skii, S V; Ryabov, E A

    2008-08-31

    The separation of nitrogen isotopes is studied upon successive single-photon IR excitation and UV dissociation of ammonia molecules. The excitation selectivity was provided by tuning a CO{sub 2} laser to resonance with {sup 14}NH{sub 3} molecules [the 9R(30) laser line] or with {sup 15}NH{sub 3} molecules [the 9R(10) laser line]. Isotopic mixtures containing 4.8% and 0.37% (natural content) of the {sup 15}NH isotope were investigated. The dependences of the selectivity and the dissociation yield for each isotopic component on the buffer gas pressure (N{sub 2}, O{sub 2}, Ar) and the ammonia pressure were obtained. In the limit of low NH{sub 3} pressures (0.5-2 Torr), the dissociation selectivity {alpha}(15/14) for {sup 15}N was 17. The selectivity mechanism of the IR+UV dissociation is discussed and the outlook is considered for the development of the nitrogen isotope separation process based on this approach. (laser isotope separation)

  15. HIV-1 entry inhibition by small-molecule CCR5 antagonists: A combined molecular modeling and mutant study using a high-throughput assay

    SciTech Connect (OSTI)

    Labrecque, Jean; Metz, Markus; Lau, Gloria; Darkes, Marilyn C.; Wong, Rebecca S.Y.; Bogucki, David; Carpenter, Bryon; Chen Gang; Li Tongshuang; Nan, Susan; Schols, Dominique; Bridger, Gary J.; Fricker, Simon P.; Skerlj, Renato T.

    2011-05-10

    Based on the attrition rate of CCR5 small molecule antagonists in the clinic the discovery and development of next generation antagonists with an improved pharmacology and safety profile is necessary. Herein, we describe a combined molecular modeling, CCR5-mediated cell fusion, and receptor site-directed mutagenesis approach to study the molecular interactions of six structurally diverse compounds (aplaviroc, maraviroc, vicriviroc, TAK-779, SCH-C and a benzyloxycarbonyl-aminopiperidin-1-yl-butane derivative) with CCR5, a coreceptor for CCR5-tropic HIV-1 strains. This is the first study using an antifusogenic assay, a model of the interaction of the gp120 envelope protein with CCR5. This assay avoids the use of radioactivity and HIV infection assays, and can be used in a high throughput mode. The assay was validated by comparison with other established CCR5 assays. Given the hydrophobic nature of the binding pocket several binding models are suggested which could prove useful in the rational drug design of new lead compounds.

  16. Single Molecule Spectroelectrochemistry of Interfacial Charge Transfer Dynamics In Hybrid Organic Solar Cell

    SciTech Connect (OSTI)

    Pan, Shanlin

    2014-11-16

    Our research under support of this DOE grant is focused on applied and fundamental aspects of model organic solar cell systems. Major accomplishments are: 1) we developed a spectroelectorchemistry technique of single molecule single nanoparticle method to study charge transfer between conjugated polymers and semiconductor at the single molecule level. The fluorescence of individual fluorescent polymers at semiconductor surfaces was shown to exhibit blinking behavior compared to molecules on glass substrates. Single molecule fluorescence excitation anisotropy measurements showed the conformation of the polymer molecules did not differ appreciably between glass and semiconductor substrates. The similarities in molecular conformation suggest that the observed differences in blinking activity are due to charge transfer between fluorescent polymer and semiconductor, which provides additional pathways between states of high and low fluorescence quantum efficiency. Similar spectroelectrochemistry work has been done for small organic dyes for understand their charge transfer dynamics on various substrates and electrochemical environments; 2) We developed a method of transferring semiconductor nanoparticles (NPs) and graphene oxide (GO) nanosheets into organic solvent for a potential electron acceptor in bulk heterojunction organic solar cells which employed polymer semiconductor as the electron donor. Electron transfer from the polymer semiconductor to semiconductor and GO in solutions and thin films was established through fluorescence spectroscopy and electroluminescence measurements. Solar cells containing these materials were constructed and evaluated using transient absorption spectroscopy and dynamic fluorescence techniques to understand the charge carrier generation and recombination events; 3) We invented a spectroelectorchemistry technique using light scattering and electroluminescence for rapid size determination and studying electrochemistry of single NPs in an electrochemical cell. For example, we are able to use this technique to track electroluminescence of single Au NPs, and the electrodeposition of individual Ag NPs in-situ. These metallic NPs are useful to enhance light harvesting in organic photovoltaic systems. The scattering at the surface of an indium tin oxide (ITO) working electrode was measured during a potential sweep. Utilizing Mie scattering theory and high resolution scanning electron microscopy (SEM), the scattering data were used to calculate current-potential curves depicting the electrodeposition of individual Ag NPs. The oxidation of individual presynthesized and electrodeposited Ag NPs was also investigated using fluorescence and DFS microscopies. Our work has produced 1 US provisional patent, 15 published manuscripts, 1 submitted and two additional in-writing manuscripts. 5 graduate students, 1 postdoctoral student, 1 visiting professor, and two undergraduate students have received research training in the area of electrochemistry and optical spectroscopy under support of this award.

  17. Reconstruction of two-dimensional molecular structure with laser-induced electron diffraction from laser-aligned polyatomic molecules

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yu, Chao; Wei, Hui; Wang, Xu; Le, Anh -Thu; Lu, Ruifeng; Lin, C. D.

    2015-10-27

    Imaging the transient process of molecules has been a basic way to investigate photochemical reactions and dynamics. Based on laser-induced electron diffraction and partial one-dimensional molecular alignment, here we provide two effective methods for reconstructing two-dimensional structure of polyatomic molecules. We demonstrate that electron diffraction images in both scattering angles and broadband energy can be utilized to retrieve complementary structure information, including positions of light atoms. Lastly, with picometre spatial resolution and the inherent femtosecond temporal resolution of lasers, laser-induced electron diffraction method offers significant opportunities for probing atomic motion in a large molecule in a typical pump-probe measurement.

  18. DFT structural investigation on Fe(1,10-phenanthroline){sub 2} (NCS){sub 2} spin crossover molecule

    SciTech Connect (OSTI)

    Chiş, V.; Isai, R.; Droghetti, A.; Rungger, I.; Sanvito, S.; Morari, C.

    2013-11-13

    Understanding the coupling of spin crossover molecules to metallic surfaces is a key ingredient for harnessing of their remarkable features for future spintronics applications. Here we investigate the structural and electronic properties of deformed Fe(1,10-phenanthroline){sub 2} (NCS){sub 2} molecules, mimicking the possible effects arising from the interaction with a metallic substrate. We find a relatively large structural flexibility for this molecule, accompanied by small changes in their total energy. This suggests that the spin crossover activity can be modulated by the interaction with the substrate.

  19. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 ALSNews Vol. 306 Print Wednesday, 24 February 2010 00:00 In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders

  20. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group Leader

  1. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group Leader

  2. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group Leader

  3. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group Leader

  4. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group Leader

  5. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    06 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group

  6. ALSNews Vol. 306

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    06 Print In This Issue 200th Science Highlight! Imaging Antifungal Drug Molecules with Soft X-Ray Tomography Electron Correlation in Iron-based Superconductors A New Route to Nano Self-Assembly Optical Metrology Lab gets New Funding ALS Winners of Mobile Application Contest Ring Leaders: User Services Announcements: Science Café Wed 3/31, Guest House Special Extended, and Top-off Celebration Operations Update UEC Corner News Links RingLeaders Ring Leaders User Services User Services Group

  7. The use of carbon stable isotope ratios in drugs characterization

    SciTech Connect (OSTI)

    Magdas, D. A. Cristea, G. Bot, A. Mirel, V.

    2013-11-13

    Isotopic Ratio Mass Spectrometry (IRMS) is an effective toll to be used for drug product authentication. The isotopic composition could be used to assist in the differentiation between batches of drugs and assist in the identification of counterfeit materials on the market. Only two factors affect the isotopic ratios in pharmaceutical components: the isotopic composition of the raw materials and the synthetic processes performed upon them. Counterfeiting of pharmaceutical drugs threatens consumer confidence in drug products companies' economical well-being. In this preliminary study, the analyzed samples consist in two types of commercially available analgesics, which were purchases from Romanian pharmacies. Differences in ?{sup 13}C between batches from ?29.7 to ?31.6% were observed, demonstrating that this method can be used to differentiate among individual drug batches and subsequently identify counterfeits on the market. On the other hand, carbon isotopic ratios differences among producers were recorded, the variations being between ?31.3 to ?34.9% for the same type of analgesic, but from different manufactures.

  8. Statistical Exploration of Electronic Structure of Molecules from Quantum Monte-Carlo Simulations

    SciTech Connect (OSTI)

    Prabhat, Mr; Zubarev, Dmitry; Lester, Jr., William A.

    2010-12-22

    In this report, we present results from analysis of Quantum Monte Carlo (QMC) simulation data with the goal of determining internal structure of a 3N-dimensional phase space of an N-electron molecule. We are interested in mining the simulation data for patterns that might be indicative of the bond rearrangement as molecules change electronic states. We examined simulation output that tracks the positions of two coupled electrons in the singlet and triplet states of an H2 molecule. The electrons trace out a trajectory, which was analyzed with a number of statistical techniques. This project was intended to address the following scientific questions: (1) Do high-dimensional phase spaces characterizing electronic structure of molecules tend to cluster in any natural way? Do we see a change in clustering patterns as we explore different electronic states of the same molecule? (2) Since it is hard to understand the high-dimensional space of trajectories, can we project these trajectories to a lower dimensional subspace to gain a better understanding of patterns? (3) Do trajectories inherently lie in a lower-dimensional manifold? Can we recover that manifold? After extensive statistical analysis, we are now in a better position to respond to these questions. (1) We definitely see clustering patterns, and differences between the H2 and H2tri datasets. These are revealed by the pamk method in a fairly reliable manner and can potentially be used to distinguish bonded and non-bonded systems and get insight into the nature of bonding. (2) Projecting to a lower dimensional subspace ({approx}4-5) using PCA or Kernel PCA reveals interesting patterns in the distribution of scalar values, which can be related to the existing descriptors of electronic structure of molecules. Also, these results can be immediately used to develop robust tools for analysis of noisy data obtained during QMC simulations (3) All dimensionality reduction and estimation techniques that we tried seem to indicate that one needs 4 or 5 components to account for most of the variance in the data, hence this 5D dataset does not necessarily lie on a well-defined, low dimensional manifold. In terms of specific clustering techniques, K-means was generally useful in exploring the dataset. The partition around medoids (pam) technique produced the most definitive results for our data showing distinctive patterns for both a sample of the complete data and time-series. The gap statistic with tibshirani criteria did not provide any distinction across the 2 dataset. The gap statistic w/DandF criteria, Model based clustering and hierarchical modeling simply failed to run on our datasets. Thankfully, the vanilla PCA technique was successful in handling our entire dataset. PCA revealed some interesting patterns for the scalar value distribution. Kernel PCA techniques (vanilladot, RBF, Polynomial) and MDS failed to run on the entire dataset, or even a significant fraction of the dataset, and we resorted to creating an explicit feature map followed by conventional PCA. Clustering using K-means and PAM in the new basis set seems to produce promising results. Understanding the new basis set in the scientific context of the problem is challenging, and we are currently working to further examine and interpret the results.

  9. Fragmentation of the adenine and guanine molecules induced by electron collisions

    SciTech Connect (OSTI)

    Minaev, B. F. E-mail: boris@theochem.kth.se; Shafranyosh, M. I.; Svida, Yu. Yu; Sukhoviya, M. I.; Shafranyosh, I. I.; Baryshnikov, G. V.; Minaeva, V. A.

    2014-05-07

    Secondary electron emission is the most important stage in the mechanism of radiation damage to DNA biopolymers induced by primary ionizing radiation. These secondary electrons ejected by the primary electron impacts can produce further ionizations, initiating an avalanche effect, leading to genome damage through the energy transfer from the primary objects to sensitive biomolecular targets, such as nitrogenous bases, saccharides, and other DNA and peptide components. In this work, the formation of positive and negative ions of purine bases of nucleic acids (adenine and guanine molecules) under the impact of slow electrons (from 0.1 till 200 eV) is studied by the crossed electron and molecular beams technique. The method used makes it possible to measure the molecular beam intensity and determine the total cross-sections for the formation of positive and negative ions of the studied molecules, their energy dependences, and absolute values. It is found that the maximum cross section for formation of the adenine and guanine positive ions is reached at about 90 eV energy of the electron beam and their absolute values are equal to 2.8 × 10{sup ?15} and 3.2 × 10{sup ?15} cm{sup 2}, respectively. The total cross section for formation of the negative ions is 6.1 × 10{sup ?18} and 7.6 × 10{sup ?18} cm{sup 2} at the energy of 1.1 eV for adenine and guanine, respectively. The absolute cross-section values for the molecular ions are measured and the cross-sections of dissociative ionization are determined. Quantum chemical calculations are performed for the studied molecules, ions and fragments for interpretation of the crossed beams experiments.

  10. Many-body electronic structure and Kondo properties of cobalt-porphyrin molecules.

    SciTech Connect (OSTI)

    Reboredo, Fernando A; Tiago, Murilo L; Dagotto, Elbio R; Dias Da Silva, Luis G; Ulloa, Sergio E

    2009-01-01

    We use a unique combination of first principles many-body methods and the numerical renormalization-group technique to study the Kondo regime of cobalt-porphyrin compounds adsorbed on a Cu(111) surface. We find the Kondo temperature to be highly sensitive to both molecule charging and distance to the surface, which can explain the variations observed in recent scanning tunneling spectroscopy measurements. We discuss the importance of manybody effects in the molecular electronic structure controlling this phenomenon and suggest scenarios where enhanced temperatures can be achieved in experiments.

  11. Observation of spectral evolution during the formation of a Ni2 kondo molecule

    SciTech Connect (OSTI)

    Madhavan, V.; Jamneala, T.; Nagaoka, K.; Chen, W.; Li, Je-Luen; Louie, Steven G.; Crommie, M.F.

    2002-04-15

    We have used atomic manipulation and scanning tunneling spectroscopy to study the evolution in electronic properties that occurs as two Ni atoms are merged into a single magnetic molecule on Au(111). We observe energetic shifting of molecular d-orbitals and a strong decrease in the molecular Kondo temperature as Ni-Ni separation is reduced to 3.4+ or -0.3Angstroms. These results are qualitatively explained by a combination of spin-1/2-s-d model and density-functional calculations.

  12. Phase transition into the metallic state in hypothetical (without molecules) dense atomic hydrogen

    SciTech Connect (OSTI)

    Khomkin, A. L. Shumikhin, A. S.

    2013-10-15

    A simple physical model of the metal-dielectric (vapor-liquid) phase transition in hypothetical (without molecules) atomic hydrogen is proposed. The reason for such a transition is the quantum collective cohesive energy occurring due to quantum electron-electron exchange similar to the cohesive energy in the liquid-metal phase of alkali metals. It is found that the critical parameters of the transition are P{sub c} ? 41000 atm, ?{sub c} ? 0.1 g/cm{sup 3}, and T{sub c} ? 9750 K.

  13. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen

    2000-01-01

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  14. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2006-10-17

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  15. Direct imaging of rotational wave-packet dynamics of diatomic molecules

    SciTech Connect (OSTI)

    Dooley, P. W.; Lee, Kevin F.; Corkum, P. B.; Litvinyuk, I. V.; Rayner, D. M.; Villeneuve, D. M.; Spanner, M.

    2003-08-01

    We use linearly polarized 45 fs pulses to create rotational wave packets in N{sub 2} and O{sub 2}. We Coulomb explode molecules with a high-intensity circularly polarized pulse and use an ion imaging detector to measure a series of two-dimensional projections of the wave packet's angular distribution in 27 fs increments. We highlight the evolving wave packet near the first, second, sixth, and tenth full revival times and also near the one-eighth, one-quarter, one-half, and three-quarter fractional revivals.

  16. Local spin torque induced by electron electric dipole moment in the YbF molecule

    SciTech Connect (OSTI)

    Fukuda, Masahiro; Senami, Masato; Ogiso, Yoji; Tachibana, Akitomo

    2014-10-06

    In this study, we show the modification of the equation of motion of the electronic spin, which is derived by the quantum electron spin vorticity principle, by the effect of the electron electric dipole moment (EDM). To investigate the new contribution to spin torque by EDM, using first principle calculations, we visualize distributions of the local spin angular momentum density and local spin torque density of the YbF molecule on which the static electric field and magnetic field are applied at t = 0.

  17. Porous materials with pre-designed single-molecule traps for CO2 selective

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    adsorption | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Porous materials with pre-designed single-molecule traps for CO2 selective adsorption Previous Next List Jian-Rong Li, Jiamei Yu, Weigang Lu, Lin-Bing Sun, Julian Sculley, Perla B. Balbuena & Hong-Cai Zhou, Nature Communications 4, Article number: 1538, 2013, DOI: 10.1038/ncomms2552 ncomms2552.html Abstract: Despite tremendous efforts, precise control in the synthesis of porous materials with

  18. Stable Metal-Organic Frameworks Containing Single-Molecule Traps for Enzyme

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Encapsulation | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Stable Metal-Organic Frameworks Containing Single-Molecule Traps for Enzyme Encapsulation Previous Next List Dawei Feng, Tian-Fu Liu, Jie Su, Mathieu Bosch, Zhangwen Wei, Wei Wan, Daqiang Yuan, Ying-Pin Chen, Xuan Wang, Kecheng Wang, Xizhen Lian, Zhi-Yuan Gu, Jihye Park, Xiaodong Zou & Hong-Cai Zhou, Nature Communications 6, 5979 (2015) DOI: 10.1038/ncomms6979 179 Abstract: Enzymatic

  19. Electromagnetic field triggered drug and chemical delivery via liposomes

    DOE Patents [OSTI]

    Liburdy, Robert P. (1820 Mountain View Rd., Tiburon, CA 94920)

    1993-01-01

    The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release said chemical agent from the liposomes at a temperature of between about +10 and 65.degree. C. The invention further relates to the use of said liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

  20. Electromagnetic field triggered drug and chemical delivery via liposomes

    DOE Patents [OSTI]

    Liburdy, R.P.

    1993-03-02

    The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release the chemical agent from the liposomes at a temperature of between about +10 and 65 C. The invention further relates to the use of the liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

  1. X-ray Spectroscopy for Quality Control of Chemotherapy Drugs

    SciTech Connect (OSTI)

    Greaves, E. D.; Barros, H.; Bermudez, J.; Sajo-Bohus, L.; Angeli-Greaves, M.

    2007-10-26

    We develop a method, employing Compton peak standardization and the use of matrix-matched spiked samples with Total Reflection X-ray Fluorescence (TXRF), for the determination of platinum plasma concentrations of patients undergoing chemotherapy with Pt-bearing drugs. Direct blood plasma analysis attains Pt detection limits of 70 ng/ml. Measurement results of prescribed drug doses are compared to achieved blood Pt concentrations indicating a lack of expected correlations. Direct analysis of Pt-containing infused drugs from a variety of suppliers indicates cases of abnormal concentrations which raises quality control issues. We demonstrate the potential usefulness of the method for pharmacokinetic studies or for routine optimization and quality control of Pt chemotherapy treatments.

  2. Collision lifetimes of polyatomic molecules at low temperatures: Benzene–benzene vs benzene–rare gas atom collisions

    SciTech Connect (OSTI)

    Cui, Jie; Krems, Roman V.; Li, Zhiying

    2014-10-28

    We use classical trajectory calculations to study the effects of the interaction strength and the geometry of rigid polyatomic molecules on the formation of long-lived collision complexes at low collision energies. We first compare the results of the calculations for collisions of benzene molecules with rare gas atoms He, Ne, Ar, Kr, and Xe. The comparison illustrates that the mean lifetimes of the collision complexes increase monotonically with the strength of the atom–molecule interaction. We then compare the results of the atom–benzene calculations with those for benzene–benzene collisions. The comparison illustrates that the mean lifetimes of the benzene–benzene collision complexes are significantly reduced due to non-ergodic effects prohibiting the molecules from sampling the entire configuration space. We find that the thermally averaged lifetimes of the benzene–benzene collisions are much shorter than those for Xe with benzene and similar to those for Ne with benzene.

  3. Reprogramming Bacteria to Seek and Destroy Small Molecules (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    SciTech Connect (OSTI)

    Gallivan, Justin [Emory University] [Emory University

    2012-03-21

    Justin Gallivan, of Emory University presents a talk titled "Reprogramming Bacteria to Seek and Destroy Small Molecules" at the JGI User 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, Calif

  4. Reprogramming Bacteria to Seek and Destroy Small Molecules (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    ScienceCinema (OSTI)

    Gallivan, Justin [Emory University

    2013-01-22

    Justin Gallivan, of Emory University presents a talk titled "Reprogramming Bacteria to Seek and Destroy Small Molecules" at the JGI User 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, Calif

  5. 2012 SINGLE MOLECULE APPROACHES TO BIOLOGY GORDON RESEARCH CONFERENCE (JULY 15-20, 2012 - MOUNT SNOW RESORT, WEST DOVER VT)

    SciTech Connect (OSTI)

    Fernandez, Julio [Columbia University

    2012-04-20

    Single molecule techniques are rapidly occupying a central role in biological research at all levels. This transition was made possible by the availability and dissemination of robust techniques that use fluorescence and force probes to track the conformation of molecules one at a time, in vitro as well as in live cells. Single-molecule approaches have changed the way many biological problems are studied. These novel techniques provide previously unobtainable data on fundamental biochemical processes that are essential for all forms of life. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of the molecular systems that underpin the functioning of living cells. Hence, our conference seeks to disseminate the implementation and use of single molecule techniques in the pursuit of new biological knowledge. Topics covered include: Molecular Motors on the Move; Origin And Fate Of Proteins; Physical Principles Of Life; Molecules and Super-resolution Microscopy; Nanoswitches In Action; Active Motion Or Random Diffusion?; Building Blocks Of Living Cells; From Molecular Mechanics To Physiology; Tug-of-war: Force Spectroscopy Of Single Proteins.

  6. Tungsten polyoxometalate molecules as active nodes for dynamic carrier exchange in hybrid molecular/semiconductor capacitors

    SciTech Connect (OSTI)

    Balliou, A.; Douvas, A. M.; Normand, P.; Argitis, P.; Glezos, N.; Tsikritzis, D.; Kennou, S.

    2014-10-14

    In this work we study the utilization of molecular transition metal oxides known as polyoxometalates (POMs), in particular the Keggin structure anions of the formula PW₁₂O₄₀³⁻, as active nodes for potential switching and/or fast writing memory applications. The active molecules are being integrated in hybrid Metal-Insulator/POM molecules-Semiconductor capacitors, which serve as prototypes allowing investigation of critical performance characteristics towards the design of more sophisticated devices. The charging ability as well as the electronic structure of the molecular layer is probed by means of electrical characterization, namely, capacitance-voltage and current-voltage measurements, as well as transient capacitance measurements, C (t), under step voltage polarization. It is argued that the transient current peaks observed are manifestations of dynamic carrier exchange between the gate electrode and specific molecular levels, while the transient C (t) curves under conditions of molecular charging can supply information for the rate of change of the charge that is being trapped and de-trapped within the molecular layer. Structural characterization via surface and cross sectional scanning electron microscopy as well as atomic force microscopy, spectroscopic ellipsometry, UV and Fourier-transform IR spectroscopies, UPS, and XPS contribute to the extraction of accurate electronic structure characteristics and open the path for the design of new devices with on-demand tuning of their interfacial properties via the controlled preparation of the POM layer.

  7. A modular molecular framework for utility in small-molecule solution-processed organic photovoltaic devices

    SciTech Connect (OSTI)

    Welch, Gregory C; Perez, Louis A.; Hoven, Corey V.; Zhang, Yuan; Dang, Xuan-Dung; Sharenko, Alexander; Toney, Michael F.; Kramer, Edward J.; Nguyen, Thuc-Quyen; Bazan, Guillermo C.

    2011-01-01

    We report on the design, synthesis and characterization of light harvesting small molecules for use in solution-processed small molecule bulk heterojunction (SM-BHJ) solar cell devices. These molecular materials are based upon an acceptor/donor/acceptor (A/D/A) core with donor endcapping units. Utilization of a dithieno(3,2-b;2',3'-d)silole (DTS) donor and pyridal[2,1,3]thiadiazole (PT) acceptor leads to strong charge transfer characteristics, resulting in broad optical absorption spectra extending well beyond 700 nm. SM-BHJ solar cell devices fabricated with the specific example 5,5'-bis{7-(4-(5-hexylthiophen-2-yl)thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-c]pyridine}-3,3'-di-2-ethylhexylsilylene-2,2'-bithiophene (6) as the donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor component showed short circuit currents above -10 mA cm-2 and power conversion efficiencies (PCEs) over 3%. Thermal processing is a critical factor in obtaining favorable active layer morphologies and high PCE values. A combination of UV-visible spectroscopy, conductive and photo-conductive atomic force microscopies, dynamic secondary mass ion spectrometry (DSIMS), and grazing incident wide angle X-ray scattering (GIWAXS) experiments were carried out to characterize how thermal treatment influences the active layer structure and organization.

  8. Nanostructures of Liquid Crystal Phases in Mixtures of Bent-core and Rod-shaped Molecules

    SciTech Connect (OSTI)

    S Hong; R Verduzco; J Gleeson; S Sprunt; A Jakli

    2011-12-31

    We report small angle x-ray scattering (SAXS) studies of isotropic, nematic, and smectic mesophases formed by binary mixtures of bent-core (BC) and rod-shaped (RS) molecules. While optical studies indicate that the components are fully miscible, SAXS reveals fascinating structures that are consistent with segregation on a nanoscopic scale. We find that tilted smectic clusters, which have been previously reported in both the nematic and isotropic states of the pure BC materials, are also present in mixtures with up to 50 wt% of the RS compound; this is consistent with previous dielectric and flexoelectric studies on such mixtures. Unexpectedly in this concentration range the clusters are present in the isotropic and in the induced smectic phase range, as well as throughout the nematic phase. The results in the smectic phase also reveal complex layering phenomena, providing important insight into the interaction between bent and rod-shaped molecules. These studies will be crucial in the design of promising new functional nanomaterials.

  9. Nanostructures of liquid crystal phases in mixtures of bent-core and rod-shaped molecules

    SciTech Connect (OSTI)

    Hong, S. H.; Gleeson, J. T.; Sprunt, S.; Verduzco, R.; Jakli, A.

    2011-06-15

    We report small angle x-ray scattering (SAXS) studies of isotropic, nematic, and smectic mesophases formed by binary mixtures of bent-core (BC) and rod-shaped (RS) molecules. While optical studies indicate that the components are fully miscible, SAXS reveals fascinating structures that are consistent with segregation on a nanoscopic scale. We find that tilted smectic clusters, which have been previously reported in both the nematic and isotropic states of the pure BC materials, are also present in mixtures with up to 50 wt% of the RS compound; this is consistent with previous dielectric and flexoelectric studies on such mixtures. Unexpectedly in this concentration range the clusters are present in the isotropic and in the induced smectic phase range, as well as throughout the nematic phase. The results in the smectic phase also reveal complex layering phenomena, providing important insight into the interaction between bent and rod-shaped molecules. These studies will be crucial in the design of promising new functional nanomaterials.

  10. A study of competitive adsorption of organic molecules onto mineral oxides using DRIFTS

    SciTech Connect (OSTI)

    Joan E. Thomas, Michael J. Kelley

    2010-02-01

    Analysis of DRIFTS spectra was used for a quantitative study of competitive adsorption of myristic and salicylic acids onto kaolinite or {gamma}-alumina. Peaks unique to the ring or the chain were selected and single molecule studies used as calibration. Samples were exposed to hexane solution containing equal molecular quantities of each acid. The surface loading of salicylic acid was not influenced by the presence of myristic acid on either mineral but the maximum loading of myristic acid was decreased (46-50%) by salicylic acid. Displacement of myristic acid from {gamma}-alumina, but not kaolinite, was observed when excess salicylic acid remained in solution. A 25% increase in the maximum loading was observed for kaolinite, but not for{gamma}-alumina. On {gamma}-alumina, after a loading of 1 molecule per nm{sup 2}, increased exposure resulted in salicylic acid adsorption only, this value is approximately the same for salicylic acid adsorption from aqueous solution or for water washed hexane treated samples. Thus a set of sites for adsorption of either acid is indicated together with other energetically less favorable sites, which can be occupied by salicylic, but not by myristic, acid.

  11. Single-molecule imaging at high fluorophore concentrations by local activation of dye

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Geertsema, Hylkje J.; Mangel, Walter F.; Schulte, Aartje C.; Spenkelink, Lisanne M.; McGrath, William J.; Morrone, Seamus R.; Sohn, Jungsan; Robinson, Andrew; van Oijen, Antoine M.

    2015-02-17

    Single-molecule fluorescence microscopy is a powerful approach to observe biomolecular interactions with high spatial and temporal resolution. Detecting fluorescent signals from individual, labeled proteins above high levels of background fluorescence remains challenging, however. For this reason, the concentrations of labeled proteins in in vitro assays are often kept low compared to their in vivo concentrations. Here, we present a new fluorescence imaging technique by which single fluorescent molecules can be observed in real time at high, physiologically relevant concentrations. The technique requires a protein and its macromolecular substrate to be labeled each with a different fluorophore. Then, making use ofmore » short-distance energy-transfer mechanisms, the fluorescence from only those proteins bound to their substrate are selectively activated. This approach is demonstrated by labeling a DNA substrate with an intercalating stain, exciting the stain, and using energy transfer from the stain to activate the fluorescence of only those labeled DNA-binding proteins bound to the DNA. Such an experimental design allowed us to observe the sequence-independent interaction of Cy5-labeled interferon-inducible protein 16 (IFI16) with DNA and the sliding via one-dimensional diffusion of Cy5-labeled adenovirus protease (pVIc-AVP) on DNA in the presence of a background of hundreds of nM Cy5 fluorophore.« less

  12. Drug release from hydrazone-containing peptide amphiphiles

    SciTech Connect (OSTI)

    Matson, John B.; Stupp, Samuel I.

    2012-03-15

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine E-amine allowed for precise placement of a hydrazide in a peptide sequence.

  13. Multiple scattering of electrons in solids and molecules: A cluster-model approach

    SciTech Connect (OSTI)

    Garcia de Abajo, F. J.; Van Hove, M. A.; Fadley, C. S.

    2001-02-15

    A method for the simulation of electron scattering and diffraction in solids and molecules within the cluster approach is presented with explicit applications to photoelectron diffraction, electron scattering in molecules, and low-energy electron diffraction. No approximations are made beyond the muffin-tin model, and, in particular, an exact representation of the free-electron Green function is used. All multiple-scattering paths are accounted for up to an order of scattering that ensures convergence. The method relies upon a convenient separation of the free-electron Green function in rotation matrices and translations along the z axis, which greatly reduces the computation time and storage demand. The evaluation of the multiple-scattering expansion is implemented using the fully convergent recursion method, which permits one to perform an iterative refinement of the final-state wave function, as expressed in the basis set of spherical harmonics attached to each atom of the cluster. Examples are offered in which the direct multiple-scattering expansion and the more elaborated simultaneous relaxation method fail to converge, whereas the recursion method leads to convergence. The computation time needed by the resulting computer program of electron diffraction in atomic clusters to determine the self-consistently scattered wave function is proportional to N{sup 2}(l{sub max}+1){sup 3}, where N is the number of atoms in the cluster and l{sub max} is the maximum angular momentum for which the scattering phase shifts take non-negligible values. Within this method it is possible to establish that in practical cases N>1000 might be needed for a convergence of the cluster size, although the angular averaging inherent in many experiments may reduce this. The recursion method was also modified to reduce the effort in computing angular distributions of photoelectrons and low-energy diffracted electrons, which now require negligible time for each angle of emission once the wave function has been determined for a given electron energy. Angle and energy distributions of core-level photoemission, elastic scattering of electrons from a free molecule, and low-energy electron diffraction in large-unit-cell surfaces are calculated.

  14. Theoretical study of the rhodium dimer interaction with the hydrogen molecule

    SciTech Connect (OSTI)

    Castillo, S.; Cruz, A.; Cuan, A.

    1995-12-31

    The C{sub 2v} potential energy surfaces for the end-on and side-on approaches of H{sub 2} to the rhodium dimer were studied through self-consistent-field (SCF) and multiconfigurational SCF calculations, followed by extensive variational plus second-order multireference Moller-Plesset perturbational configuration interaction (CIPSI) calculations. Relativistic effective core potentials were used to replace the core electrons of the rhodium atoms. Together with the Rh{sub 2}-H{sub 2} interaction, the spectroscopic constants for the {sup 5}{summation}{sub g}{sup +}, {sup 1}{summation}{sub g}{sup +}, {sup 3}II{sub {mu}}, and {sup 1}II{sub {mu}} states of Rh{sub 2} are reported. It was found that the potential energy curves of the parallel and the perpendicular Rh{sub 2}({sup 5}{summation}{sub g}) interaction with H{sub 2} show that the rhodium dimer has the ability to capture and break the H{sub 2} molecule. The parallel interaction presents a soft potential barrier of 7.8 kcal/mol, energy necessary to surmount before the capture and breaking of the H-H bond. In the perpendicular interaction, Rh{sub 2} captures and breaks spontaneously H{sub 2}. The potential energy curve of the parallel Rh{sub 2}({sup 1}{summation}{sub g}) + H{sub 2} interaction shows that Rh{sub 2} also captures and breaks spontaneously the H{sub 2}, with a very deep well of 92.7 kcal/mol, while in the perpendicular approach, Rh{sub 2} has to surmount again a soft barrier of 5.2 kcal/mol to capture and break the H{sub 2} molecule. Finally, the energy curves of the parallel Rh{sub 2}({sup 1,3}II{sub {mu}}) + H{sub 2} interactions present capture and breaking with very small barriers. The perpendicular interactions capture and scisse the hydrogen molecule spontaneously. 35 refs., 6 tabs.

  15. A numerical study of the phase behaviors of drug particle/star triblock copolymer mixtures in dilute solutions for drug carrier application

    SciTech Connect (OSTI)

    Wang, Shanhui; Tong, Chaohui; Zhu, Yuejin

    2014-04-14

    The complex microstructures of drug particle/ABA star triblock copolymer in dilute solutions have been investigated by a theoretical approach which combines the self-consistent field theory and the hybrid particle-field theory. Simulation results reveal that, when the volume fraction of drug particles is smaller than the saturation concentration, the drug particle encapsulation efficiency is 100%, and micelle loading capacity increases with increasing particle volume fraction. When the volume fraction of drug particles is equal to the saturation concentration, the micelles attain the biggest size, and micelle loading capacity reaches a maximum value which is independent of the copolymer volume fraction. When the volume fraction of drug particles is more than the saturation concentration, drug particle encapsulation efficiency decreases with increasing volume fraction of drug particles. Furthermore, it is found that the saturation concentration scales linearly with the copolymer volume fraction. The above simulation results are in good agreement with experimental results.

  16. Solution-Procesed Small-Molecule OLED Luminaire for Interior Illumination

    SciTech Connect (OSTI)

    Parker, Ian

    2012-02-29

    Prototype lighting panels and luminaires were fabricated using DuPont Displaysâ?? solution-processed small-molecule OLED technology. These lighting panels were based on a spatially-patterned, 3-color design, similar in concept to an OLED display panel, with materials chosen to maximize device efficacy. The majority of the processing steps take place in air (rather than high vacuum). Optimization of device architecture, processing and construction was undertaken, with a final prototype design of 50 cm{sup 2} being fabricated and tested. Performance of these panels reached 35 lm/W at illuminant-A. A unique feature of this technology is the ability to color tune the emission, and color temperatures ranging from 2700 to > 6,500K were attained in the final build. Significant attention was paid to low-cost fabrication techniques.

  17. The crystal structure of methane B at 8 GPa—An ?-Mn arrangement of molecules

    SciTech Connect (OSTI)

    Maynard-Casely, H. E. Lundegaard, L. F.; Loa, I.; McMahon, M. I.; Gregoryanz, E.; Nelmes, R. J.; Loveday, J. S.

    2014-12-21

    From a combination of powder and single-crystal synchrotron x-ray diffraction data we have determined the carbon substructure of phase B of methane at a pressure of ?8 GPa. We find this substructure to be cubic with space group I4{sup ¯}3m and 58 molecules in the unit cell. The unit cell has a lattice parameter a = 11.911(1) Å at 8.3(2) GPa, which is a factor of ?2 larger than had previously been proposed by Umemoto et al. [J. Phys.: Condens. Matter 14, 10675 (2002)]. The substructure as now solved is not related to any close-packed arrangement, contrary to previous proposals. Surprisingly, the arrangement of the carbon atoms is isostructural with that of ?-manganese at ambient conditions.

  18. Exciton dissociation and interdot transport in CdSe quantum-dot molecules

    SciTech Connect (OSTI)

    Franceschetti, Alberto; Zunger, Alex

    2001-04-15

    One of the most important parameters that determine the transport properties of a quantum dot array is the exciton dissociation energy, i.e., the energy {Delta}E required to dissociate an exciton into an electron and a hole localized in different dots. We show that a pseudopotential calculation for a dot molecule, coupled with a basic configuration interaction calculation of the exciton energy levels, provides directly the exciton dissociation energy, including the effects of wave function overlap, screened Coulomb attraction between the electron and the hole in different dots, and polarization effects. We find that {Delta}E decreases as the interdot distance decreases and as the dielectric constant of the medium increases.

  19. Collision dynamics of polyatomic molecules containing carbon rings at low temperatures

    SciTech Connect (OSTI)

    Li, Zhiying; Heller, Eric J.; Krems, Roman V.

    2014-09-14

    We explore the collision dynamics of complex hydrocarbon molecules (benzene, coronene, adamantane, and anthracene) containing carbon rings in a cold buffer gas of {sup 3}He. For benzene, we present a comparative analysis of the fully classical and fully quantum calculations of elastic and inelastic scattering cross sections at collision energies between 1 and 10 cm{sup ?1}. The quantum calculations are performed using the time-independent coupled channel approach and the coupled-states approximation. We show that the coupled-states approximation is accurate at collision energies between 1 and 20 cm{sup ?1}. For the classical dynamics calculations, we develop an approach exploiting the rigidity of the carbon rings and including low-energy vibrational modes without holonomic constraints. Our results illustrate the effect of the molecular shape and the vibrational degrees of freedom on the formation of long-lived resonance states that lead to low-temperature clustering.

  20. High resolution mass spectrometry method and system for analysis of whole proteins and other large molecules

    DOE Patents [OSTI]

    Reilly, Peter T. A. (Knoxville, TN) [Knoxville, TN; Harris, William A. (Naperville, IL) [Naperville, IL

    2010-03-02

    A matrix assisted laser desorption/ionization (MALDI) method and related system for analyzing high molecular weight analytes includes the steps of providing at least one matrix-containing particle inside an ion trap, wherein at least one high molecular weight analyte molecule is provided within the matrix-containing particle, and MALDI on the high molecular weight particle while within the ion trap. A laser power used for ionization is sufficient to completely vaporize the particle and form at least one high molecular weight analyte ion, but is low enough to avoid fragmenting the high molecular weight analyte ion. The high molecular weight analyte ion is extracted out from the ion trap, and is then analyzed using a detector. The detector is preferably a pyrolyzing and ionizing detector.

  1. Mixtures of ions and amphiphilic molecules in slit-like pores: A density functional approach

    SciTech Connect (OSTI)

    Pizio, O.; R?ysko, W. Soko?owski, S.; Soko?owska, Z.

    2015-04-28

    We investigate microscopic structure and thermodynamic properties of a mixture that contains amphiphilic molecules and charged hard spheres confined in slit-like pores with uncharged hard walls. The model and the density functional approach are the same as described in details in our previous work [Pizio et al., J. Chem. Phys. 140, 174706 (2014)]. Our principal focus is in exploring the effects brought by the presence of ions on the structure of confined amphiphilic particles. We have found that for some cases of anisotropic interactions, the change of the structure of confined fluids occurs via the first-order transitions. Moreover, if anions and cations are attracted by different hemispheres of amphiphiles, a charge at the walls appears at the zero value of the wall electrostatic potential. For a given thermodynamic state, this charge is an oscillating function of the pore width.

  2. Interaction of mineral surfaces with simple organci molecules by diffuse reflectance IR spectroscopy (DRIFT)

    SciTech Connect (OSTI)

    Joan Thomas; Michael Kelley

    2007-06-18

    Diffuse reflectance Fourier-transform infrared spectroscopy (DRIFTS) was used to characterize multi-layers of lysine, glutamic acid and salicylic acid on ?-alumina and kaolinite surfaces. The results agreed well with those previously obtained by ATR-IR in aqueous media where available, indicating that DRIFT may be regarded as effectively an in-situ spectroscopy for these materials. In the case of salicylic acid adsorption onto ?-alumina, DRIFTS was used to identify monolayer coverage and to detect molecules down to coverage of 3% of a monolayer. The spectroscopic results as to coverage were confirmed by analysis of the solutions used for treatment. The spectra obtained allowed identification of changes in the bonding environment with increasing surface coverage. DRIFTS, offers several advantages in terms of materials, experimental technique and data treatment, motivating further investigations.

  3. Crystallography Without Crystals: Determining the Structure of Individual Biological Molecules and Nanoparticles

    ScienceCinema (OSTI)

    Ourmazd, Abbas [University of Wisconsin, Milwaukee, Wisconsin, USA

    2010-01-08

    Ever shattered a valuable vase into 10 to the 6th power pieces and tried to reassemble it under a light providing a mean photon count of 10 minus 2 per detector pixel with shot noise? If you can do that, you can do single-molecule crystallography. This talk will outline how this can be done in principle. In more technical terms, the talk will describe how the combination of scattering physics and Bayesian algorithms can be used to reconstruct the 3-D diffracted intensity distribution from a collection of individual 2-D diffiraction patterns down to a mean photon count of 10 minus 2 per pixel, the signal level anticipated from the Linac Coherent Light Source, and hence determine the structure of individual macromolecules and nanoparticles.

  4. Enhancement of ultracold molecule formation by local control in the nanosecond regime

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Carini, J. L.; Kallush, S.; Kosloff, R.; Gould, P. L.

    2015-02-01

    We describe quantum simulations of ultracold 87Rb2 molecule formation using photoassociation (PA) with nanosecond-time-scale pulses of frequency chirped light. In particular, we compare the case of a linear chirp to one where the frequency evolution is optimized by local control (LC) of the phase, and find that LC can provide a significant enhancement. The resulting optimal frequency evolution corresponds to a rapid jump from the PA absorption resonance to a downward transition to a bound level of the lowest triplet state. We also consider the case of two frequencies and investigate interference effects. The assumed chirp parameters should be achievablemore »with nanosecond pulse shaping techniques and are predicted to provide a significant enhancement over recent experiments with linear chirps.« less

  5. Single-Molecule Dynamics Reveals Cooperative Binding-Folding in Protein Recognition

    SciTech Connect (OSTI)

    Wang, Jin; Lu, Qiang N.; Lu, H PETER.

    2006-07-01

    The study of associations between two biomolecules is the key to understand molecular recognition and function. Molecular function is often thought to be determined by the underlying structures. Here, combining single molecule study of protein binding with an energy landscape inspired microscopic model, we found strong evidences that bio-molecular recognition is determined by flexibilities in addition to structures. Our model is based on coarse grained molecular dynamics performed on the residue level with the energy function biased towards the native binding structure (Go model). With our model, the underlying free energy landscape of the binding can be explored. Two distinct conformational states as free energy minimum, one with partially folding of CBD and significant binding of CBD to CDC42, and another with native folding of CBD and native binding of CBD to CDC42, are clearly seen. This shows the binding process proceeds with significant interface binding of CBD with CDC42 first without complete folding of CBD. Finally binding and folding are coupled with each other cooperatively to reach the native binding state. The single molecule experimental finding of the dynamic fluctuations between the loosely bound and closely bound conformational states can be identified with theoretically calculated free energy minimum and quantitatively explained in our model as a result of binding associated with large conformational changes. Theoretical predictions have identified certain key residues for binding which are consistent with mutational experiments. The combined study provides a test ground for fundamental mechanisms as well as insights into design and further explorations on biomolecular recognition with large conformational changes.

  6. Sensitivity of transitions in internal rotor molecules to a possible variation of the proton-to-electron mass ratio

    SciTech Connect (OSTI)

    Jansen, Paul; Ubachs, Wim; Bethlem, Hendrick L.; Kleiner, Isabelle; Xu, Li-Hong

    2011-12-15

    Recently, methanol was identified as a sensitive target system to probe variations of the proton-to-electron mass ratio {mu}[Jansen et al., Phys. Rev. Lett. 106, 100801 (2011)]. The high sensitivity of methanol originates from the interplay between overall rotation and hindered internal rotation of the molecule; that is, transitions that convert internal rotation energy into overall rotation energy, or vice versa, have an enhanced sensitivity coefficient, K{sub {mu}}. As internal rotation is a common phenomenon in polyatomic molecules, it is likely that other molecules display similar or even larger effects. In this paper we generalize the concepts that form the foundation of the high sensitivity in methanol and use this to construct an approximate model which makes it possible to estimate the sensitivities of transitions in internal rotor molecules with C{sub 3v} symmetry, without performing a full calculation of energy levels. We find that a reliable estimate of transition sensitivities can be obtained from the three rotational constants (A, B, and C) and three torsional constants (F, V{sub 3}, and {rho}). This model is verified by comparing obtained sensitivities for methanol, acetaldehyde, acetamide, methyl formate, and acetic acid with a full analysis of the molecular Hamiltonian. Of the molecules considered, methanol is by far the most suitable candidate for laboratory and cosmological tests searching for a possible variation of {mu}.

  7. VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

    SciTech Connect (OSTI)

    Vedani, Angelo; Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel ; Dobler, Max; Smieško, Martin

    2012-06-01

    The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen ?, estrogen ?, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor ?, progesterone, thyroid ?, and thyroid ?), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ? In silico technology for estimating the toxic potential of drugs and chemicals. ? Simulation of binding towards 16 proteins suspected to trigger adverse effects. ? Mechanistic interpretation and real-time 3D visualization. ? Accessible over the Internet. ? Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

  8. On the importance of nuclear quantum motions in near edge x-ray absorption fine structure (NEXAFS) spectroscopy of molecules

    SciTech Connect (OSTI)

    Schwartz, Craig P.; Uejio, Janel S.; Saykally, Richard J.; Prendergast, David

    2009-02-26

    We report the effects of sampling nuclear quantum motion with path integral molecular dynamics (PIMD) on calculations of the nitrogen K-edge spectra of two isolated organic molecules. S-triazine, a prototypical aromatic molecule occupying primarily its vibrational ground state at room temperature, exhibits substantially improved spectral agreement when nuclear quantum effects are included via PIMD, as compared to the spectra obtained from either a single fixed-nuclei based calculation or from a series of configurations extracted from a classical molecular dynamics trajectory. Nuclear quantum dynamics can accurately explain the intrinsic broadening of certain features. Glycine, the simplest amino acid, is problematic due to large spectral variations associated with multiple energetically accessible conformations at the experimental temperature. This work highlights the sensitivity of NEXAFS to quantum nuclear motions in molecules, and the necessity of accurately sampling such quantum motion when simulating their NEXAFS spectra.

  9. Separation and counting of single molecules through nanofluidics, programmable electrophoresis, and nanoelectrode-gated tunneling and dielectric detection

    DOE Patents [OSTI]

    Lee, James W.; Thundat, Thomas G.

    2006-04-25

    An apparatus for carrying out the separation, detection, and/or counting of single molecules at nanometer scale. Molecular separation is achieved by driving single molecules through a microfluidic or nanofluidic medium using programmable and coordinated electric fields. In various embodiments, the fluidic medium is a strip of hydrophilic material on nonconductive hydrophobic surface, a trough produced by parallel strips of hydrophobic nonconductive material on a hydrophilic base, or a covered passageway produced by parallel strips of hydrophobic nonconductive material on a hydrophilic base together with a nonconductive cover on the parallel strips of hydrophobic nonconductive material. The molecules are detected and counted using nanoelectrode-gated electron tunneling methods, dielectric monitoring, and other methods.

  10. Artificial Cells for Advanced Drug Delivery - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biomass and Biofuels Biomass and Biofuels Find More Like This Return to Search Artificial Cells for Advanced Drug Delivery Colorado School of Mines Contact CSM About This Technology Technology Marketing SummaryThis invention takes advantage of the unique surface chemistry of a ZnO crystalline nanostructure to catalyze a variety of chemical reactions. DescriptionOne such reaction is the hydrogenation of carbon dioxide to methanol. Alcohols interacts both molecularly and dissociatively with the

  11. FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein Structure Data Taken at ALS FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein Structure Data...

  12. Signatures of the molecular potential in the ellipticity of high-order harmonics from aligned molecules

    SciTech Connect (OSTI)

    Sherratt, Paul A. J.; Ramakrishna, S.; Seideman, Tamar

    2011-05-15

    We explore the information content of the polarization of high-order harmonics emitted from aligned molecules driven by a linearly polarized field. The study builds upon our previous work [Ramakrishna et al., Phys. Rev. A 81, 021802(R) (2010)], which illustrated that the phase of the continuum electronic wave function, and hence the underlying molecular potential, is responsible, at least in part, for the ellipticity observed in harmonic spectra. We use a simple model potential and systematically vary the potential parameters to investigate the sense in which, and the degree to which, the shape of the molecular potential is imprinted onto the polarization of the emitted harmonics. Strong ellipticity is observed over a wide range of potential parameters, suggesting that the emission of elliptically polarized harmonics is a general phenomenon, yet qualitatively determined by the molecular properties. The sensitivity of the ellipticity to the model parameters invites the use of ellipticity measurements as a probe of the continuum wave function and the underlying molecular potential.

  13. Molecule-based approach for computing chemical-reaction rates in upper atmosphere hypersonic flows.

    SciTech Connect (OSTI)

    Gallis, Michail A.; Bond, Ryan Bomar; Torczynski, John Robert

    2009-08-01

    This report summarizes the work completed during FY2009 for the LDRD project 09-1332 'Molecule-Based Approach for Computing Chemical-Reaction Rates in Upper-Atmosphere Hypersonic Flows'. The goal of this project was to apply a recently proposed approach for the Direct Simulation Monte Carlo (DSMC) method to calculate chemical-reaction rates for high-temperature atmospheric species. The new DSMC model reproduces measured equilibrium reaction rates without using any macroscopic reaction-rate information. Since it uses only molecular properties, the new model is inherently able to predict reaction rates for arbitrary nonequilibrium conditions. DSMC non-equilibrium reaction rates are compared to Park's phenomenological non-equilibrium reaction-rate model, the predominant model for hypersonic-flow-field calculations. For near-equilibrium conditions, Park's model is in good agreement with the DSMC-calculated reaction rates. For far-from-equilibrium conditions, corresponding to a typical shock layer, the difference between the two models can exceed 10 orders of magnitude. The DSMC predictions are also found to be in very good agreement with measured and calculated non-equilibrium reaction rates. Extensions of the model to reactions typically found in combustion flows and ionizing reactions are also found to be in very good agreement with available measurements, offering strong evidence that this is a viable and reliable technique to predict chemical reaction rates.

  14. Universal and nonuniversal statistical properties of levels and intensities for chaotic Rydberg molecules

    SciTech Connect (OSTI)

    Lombardi, M.; Seligman, T.H. (Laboratoire de Spectrometrie Physique-Universite Joseph Fourier de Grenoble, Boite Postale No. 87, 38402 Saint Martin d'Heres, CEDEX (France))

    1993-05-01

    We study Rydberg molecules taking into account the interaction between the rotational motion of the nuclei and the radial motion of the electron. This situation can be treated to a good approximation in quantum mechanics by the multichannel quantum-defect method which in turn has a well-defined classical limit. We are able to calculate very long sequences of levels and the corresponding amplitudes of wave packets. This allows us to study the statistical properties of both in detail. Our interest focuses on aspects of quantum chaos'' that can be particularly well understood in this case. Our main result is that, in a completely chaotic classical situation, where statistics of quantum-level spacings follow the expected universal Gaussian-orthogonal-ensemble behavior, and statistics of line intensities display the expected universal Porter-Thomas behavior, nonuniversal properties are explicitly contained in correlations between intensities and spacings, determined by the time needed for the classical system to mix on a length scale given by the quantum wavelength.

  15. Efficient solution-processed small molecule: Cadmium selenide quantum dot bulk heterojunction solar cells

    SciTech Connect (OSTI)

    Gupta, Vinay; Department of Physics, University of California, Santa Barbara, California 93106 ; Upreti, Tanvi; Chand, Suresh

    2013-12-16

    We report bulk heterojunction solar cells based on blends of solution-processed small molecule [7,7?-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b?]dithiophene-2,6-diyl) bis(6-fluoro-4-(5?-hexyl-[2,2?-bithiophen]-5yl)benzo[c] [1,2,5] thiadiazole)] p-DTS(FBTTh{sub 2}){sub 2}: Cadmium Selenide (CdSe) (70:30, 60:40, 50:50, and 40:60) in the device configuration: Indium Tin Oxide /poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/p-DTS(FBTTh{sub 2}){sub 2}: CdSe/Ca/Al. The optimized ratio of p-DTS(FBTTh{sub 2}){sub 2}:CdSe::60:40 leads to a short circuit current density (J{sub sc})?=?5.45?mA/cm{sup 2}, open circuit voltage (V{sub oc})?=?0.727?V, and fill factor (FF)?=?51%, and a power conversion efficiency?=?2.02% at 100 mW/cm{sup 2} under AM1.5G illumination. The J{sub sc} and FF are sensitive to the ratio of p-DTS(FBTTh{sub 2}){sub 2}:CdSe, which is a crucial factor for the device performance.

  16. A single-molecule approach to ZnO defect studies: Single photons and single defects

    SciTech Connect (OSTI)

    Jungwirth, N. R.; Pai, Y. Y.; Chang, H. S.; MacQuarrie, E. R.; Nguyen, K. X.; Fuchs, G. D.

    2014-07-28

    Investigations that probe defects one at a time offer a unique opportunity to observe properties and dynamics that are washed out of ensemble measurements. Here, we present confocal fluorescence measurements of individual defects in ZnO nanoparticles and sputtered films that are excited with sub-bandgap energy light. Photon correlation measurements yield both antibunching and bunching, indicative of single-photon emission from isolated defects that possess a metastable shelving state. The single-photon emission is in the range of ?560–720?nm and typically exhibits two broad spectral peaks separated by ?150?meV. The excited state lifetimes range from 1 to 13?ns, consistent with the finite-size and surface effects of nanoparticles and small grains. We also observe discrete jumps in the fluorescence intensity between a bright state and a dark state. The dwell times in each state are exponentially distributed and the average dwell time in the bright (dark) state does (may) depend on the power of the exciting laser. Taken together, our measurements demonstrate the utility of a single-molecule approach to semiconductor defect studies and highlight ZnO as a potential host material for single-defect based applications.

  17. Assessment of approximate computational methods for conical intersections and branching plane vectors in organic molecules

    SciTech Connect (OSTI)

    Nikiforov, Alexander; Gamez, Jose A.; Thiel, Walter; Huix-Rotllant, Miquel; Filatov, Michael

    2014-09-28

    Quantum-chemical computational methods are benchmarked for their ability to describe conical intersections in a series of organic molecules and models of biological chromophores. Reference results for the geometries, relative energies, and branching planes of conical intersections are obtained using ab initio multireference configuration interaction with single and double excitations (MRCISD). They are compared with the results from more approximate methods, namely, the state-interaction state-averaged restricted ensemble-referenced Kohn-Sham method, spin-flip time-dependent density functional theory, and a semiempirical MRCISD approach using an orthogonalization-corrected model. It is demonstrated that these approximate methods reproduce the ab initio reference data very well, with root-mean-square deviations in the optimized geometries of the order of 0.1 Å or less and with reasonable agreement in the computed relative energies. A detailed analysis of the branching plane vectors shows that all currently applied methods yield similar nuclear displacements for escaping the strong non-adiabatic coupling region near the conical intersections. Our comparisons support the use of the tested quantum-chemical methods for modeling the photochemistry of large organic and biological systems.

  18. Sequential data assimilation for single-molecule FRET photon-counting data

    SciTech Connect (OSTI)

    Matsunaga, Yasuhiro; Kidera, Akinori; Sugita, Yuji

    2015-06-07

    Data assimilation is a statistical method designed to improve the quality of numerical simulations in combination with real observations. Here, we develop a sequential data assimilation method that incorporates one-dimensional time-series data of smFRET (single-molecule Förster resonance energy transfer) photon-counting into conformational ensembles of biomolecules derived from “replicated” molecular dynamics (MD) simulations. A particle filter using a large number of “replicated” MD simulations with a likelihood function for smFRET photon-counting data is employed to screen the conformational ensembles that match the experimental data. We examine the performance of the method using emulated smFRET data and coarse-grained (CG) MD simulations of a dye-labeled polyproline-20. The method estimates the dynamics of the end-to-end distance from smFRET data as well as revealing that of latent conformational variables. The particle filter is also able to correct model parameter dependence in CG MD simulations. We discuss the applicability of the method to real experimental data for conformational dynamics of biomolecules.

  19. Photo-assisted intersystem crossing: The predominant triplet formation mechanism in some isolated polycyclic aromatic molecules excited with pulsed lasers

    SciTech Connect (OSTI)

    Johnson, Philip M.; Sears, Trevor J.

    2015-07-28

    Naphthalene, anthracene, and phenanthrene are shown to have very long-lived triplet lifetimes when the isolated molecules are excited with nanosecond pulsed lasers resonant with the lowest singlet state. For naphthalene, triplet state populations are created only during the laser pulse, excluding the possibility of normal intersystem crossing at the one photon level, and all molecules have triplet lifetimes greater than hundreds of microseconds, similar to the behavior previously reported for phenylacetylene. Although containing 7–12 thousand cm⁻¹ of vibrational energy, the triplet molecules have ionization thresholds appropriate to vibrationless T₁ states. The laser power dependences (slopes of log-log power plots) of the excited singlet and triplet populations are about 0.7 for naphthalene and about 0.5 for anthracene. Kinetic modeling of the power dependences successfully reproduces the experimental results and suggests that the triplet formation mechanism involves an enhanced spin orbit coupling caused by sigma character in states at the 2-photon level. Symmetry Adapted Cluster-Configuration Interaction calculations produced excited state absorption spectra to provide guidance for estimating kinetic rates and the sigma character present in higher electronic states. It is concluded that higher excited state populations are significant when larger molecules are excited with pulsed lasers and need to be taken into account whenever discussing the molecular photodynamics.

  20. Photoluminescence Enhancement in CdSe/ZnS–DNA linked–Au Nanoparticle Heterodimers Probed by Single Molecule Spectroscopy

    SciTech Connect (OSTI)

    Cotlet, M.; Maye, M.M.; Gang, O.

    2010-07-26

    Photoluminescence enhancement of up to 20 fold is demonstrated at the single molecule level for heterodimers composed of a core/shell CdSe/ZnS semiconductive quantum dot and a gold nanoparticle of 60 nm size separated by a 32 nm-long dsDNA linker when employing optical excitation at wavelengths near the surface plasmon resonance of the gold nanoparticle.

  1. Frontiers in Laser Cooling, Single-Molecule Biophysics, and Enrgy Science: A Talk from Leo Holberg and Allen Mills

    ScienceCinema (OSTI)

    Holberg, Leo; Mills, Allen [NIST

    2011-04-28

    Leo Holberg and Allen Mills present a talk at Frontiers in Laser Cooling, Single-Molecule Biophysics and Energy Science, a scientific symposium honoring Steve Chu, director of Lawrence Berkeley National Laboratory and recipient of the 1997 Nobel Prize in Physics. The symposium was held August 30, 2008 in Berkeley.

  2. Integration of biological ion channels onto optically addressable micro-fluidic electrode arrays for single molecule characterization.

    SciTech Connect (OSTI)

    Brozik, Susan Marie; Frink, Laura J. Douglas; Bachand, George David; Keller, David J.; Patrick, Elizabeth L.; Marshall, Jason A.; Ortiz, Theodore P.; Meyer, Lauren A.; Davis, Ryan W.; Brozik, James A.; Flemming, Jeb Hunter

    2004-12-01

    The challenge of modeling the organization and function of biological membranes on a solid support has received considerable attention in recent years, primarily driven by potential applications in biosensor design. Affinity-based biosensors show great promise for extremely sensitive detection of BW agents and toxins. Receptor molecules have been successfully incorporated into phospholipid bilayers supported on sensing platforms. However, a collective body of data detailing a mechanistic understanding of membrane processes involved in receptor-substrate interactions and the competition between localized perturbations and delocalized responses resulting in reorganization of transmembrane protein structure, has yet to be produced. This report describes a systematic procedure to develop detailed correlation between (recognition-induced) protein restructuring and function of a ligand gated ion channel by combining single molecule fluorescence spectroscopy and single channel current recordings. This document is divided into three sections: (1) reported are the thermodynamics and diffusion properties of gramicidin using single molecule fluorescence imaging and (2) preliminary work on the 5HT{sub 3} serotonin receptor. Thirdly, we describe the design and fabrication of a miniaturized platform using the concepts of these two technologies (spectroscopic and single channel electrochemical techniques) for single molecule analysis, with a longer term goal of using the physical and electronic changes caused by a specific molecular recognition event as a transduction pathway in affinity based biosensors for biotoxin detection.

  3. Photo-assisted intersystem crossing: The predominant triplet formation mechanism in some isolated polycyclic aromatic molecules excited with pulsed lasers

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Johnson, Philip M.; Sears, Trevor J.

    2015-07-28

    Naphthalene, anthracene, and phenanthrene are shown to have very long-lived triplet lifetimes when the isolated molecules are excited with nanosecond pulsed lasers resonant with the lowest singlet state. For naphthalene, triplet state populations are created only during the laser pulse, excluding the possibility of normal intersystem crossing at the one photon level, and all molecules have triplet lifetimes greater than hundreds of microseconds, similar to the behavior previously reported for phenylacetylene. Although containing 7–12 thousand cm⁻¹ of vibrational energy, the triplet molecules have ionization thresholds appropriate to vibrationless T₁ states. The laser power dependences (slopes of log-log power plots) ofmore » the excited singlet and triplet populations are about 0.7 for naphthalene and about 0.5 for anthracene. Kinetic modeling of the power dependences successfully reproduces the experimental results and suggests that the triplet formation mechanism involves an enhanced spin orbit coupling caused by sigma character in states at the 2-photon level. Symmetry Adapted Cluster-Configuration Interaction calculations produced excited state absorption spectra to provide guidance for estimating kinetic rates and the sigma character present in higher electronic states. It is concluded that higher excited state populations are significant when larger molecules are excited with pulsed lasers and need to be taken into account whenever discussing the molecular photodynamics.« less

  4. Observation of cold Rb{sub 2} molecules trapped in an optical dipole trap using a laser-pulse-train technique

    SciTech Connect (OSTI)

    Menegatti, Carlos R.; Marangoni, Bruno S.; Marcassa, Luis G.

    2011-11-15

    In this work, we have developed and characterized a laser-pulse-train technique to observe cold Rb{sub 2} molecules trapped in an optical dipole trap. The molecules are produced in a magneto-optical trap, and then loaded into a crossed optical dipole trap. The time evolution of the molecular population is obtained by applying a laser pulse train, which photoionizes the ground-state molecules through intermediate molecular bands. Our results show that this technique allows us to obtain a faster data acquisition rate of the time evolution of the molecule population than other techniques.

  5. Two-photon Photoemission of Organic Semiconductor Molecules on Ag(111)

    SciTech Connect (OSTI)

    Yang, Aram; Yang, Aram

    2008-05-15

    Angle- and time-resolved two-photon photoemission (2PPE) was used to study systems of organic semiconductors on Ag(111). The 2PPE studies focused on electronic behavior specific to interfaces and ultrathin films. Electron time dynamics and band dispersions were characterized for ultrathin films of a prototypical n-type planar aromatic hydrocarbon, PTCDA, and representatives from a family of p-type oligothiophenes.In PTCDA, electronic behavior was correlated with film morphology and growth modes. Within a fewmonolayers of the interface, image potential states and a LUMO+1 state were detected. The degree to which the LUMO+1 state exhibited a band mass less than a free electron mass depended on the crystallinity of the layer. Similarly, image potential states were measured to have free electron-like effective masses on ordered surfaces, and the effective masses increased with disorder within the thin film. Electron lifetimes were correlated with film growth modes, such that the lifetimes of electrons excited into systems created by layer-by-layer, amorphous film growth increased by orders of magnitude by only a few monolayers from the surface. Conversely, the decay dynamics of electrons in Stranski-Krastanov systems were limited by interaction with the exposed wetting layer, which limited the barrier to decay back into the metal.Oligothiophenes including monothiophene, quaterthiophene, and sexithiophene were deposited on Ag(111), and their electronic energy levels and effective masses were studied as a function of oligothiophene length. The energy gap between HOMO and LUMO decreased with increasing chain length, but effective mass was found to depend on domains from high- or low-temperature growth conditions rather than chain length. In addition, the geometry of the molecule on the surface, e.g., tilted or planar, substantially affected the electronic structure.

  6. Size-dependent fluorescence of bioaerosols: Mathematical model using fluorescing and absorbing molecules in bacteria

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hill, Steven C.; Williamson, Chatt C.; Doughty, David C.; Pan, Yong-Le; Santarpia, Joshua L.; Hill, Hanna H.

    2015-02-02

    This paper uses a mathematical model of fluorescent biological particles composed of bacteria and/or proteins (mostly as in Hill et al., 2013 [23]) to investigate the size-dependence of the total fluorescence emitted in all directions. The model applies to particles which have negligible reabsorption of fluorescence within the particle. The specific particles modeled here are composed of ovalbumin and of a generic Bacillus. The particles need not be spherical, and in some cases need not be homogeneous. However, the results calculated in this paper are for spherical homogeneous particles. Light absorbing and fluorescing molecules included in the model are aminomore » acids, nucleic acids, and several coenzymes. Here the excitation wavelength is 266 nm. The emission range, 300 to 370 nm, encompasses the fluorescence of tryptophan. The fluorescence cross section (CF) is calculated and compared with one set of published measured values. We investigate power law (Ady) approximations to CF, where d is diameter, and A and y are parameters adjusted to fit the data, and examine how y varies with d and composition, including the fraction as water. The particle's fluorescence efficiency (QF=CF/geometric-cross-section) can be written for homogeneous particles as QabsRF, where Qabs is the absorption efficiency, and RF, the fraction of the absorbed light emitted as fluorescence, is independent of size and shape. When QF is plotted vs. mid or mi(mr-1)d, where m=mr+imi is the complex refractive index, the plots for different fractions of water in the particle tend to overlap.« less

  7. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    SciTech Connect (OSTI)

    O'Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC).

  8. Size-dependent fluorescence of bioaerosols: Mathematical model using fluorescing and absorbing molecules in bacteria

    SciTech Connect (OSTI)

    Hill, Steven C.; Williamson, Chatt C.; Doughty, David C.; Pan, Yong-Le; Santarpia, Joshua L.; Hill, Hanna H.

    2015-02-02

    This paper uses a mathematical model of fluorescent biological particles composed of bacteria and/or proteins (mostly as in Hill et al., 2013 [23]) to investigate the size-dependence of the total fluorescence emitted in all directions. The model applies to particles which have negligible reabsorption of fluorescence within the particle. The specific particles modeled here are composed of ovalbumin and of a generic Bacillus. The particles need not be spherical, and in some cases need not be homogeneous. However, the results calculated in this paper are for spherical homogeneous particles. Light absorbing and fluorescing molecules included in the model are amino acids, nucleic acids, and several coenzymes. Here the excitation wavelength is 266 nm. The emission range, 300 to 370 nm, encompasses the fluorescence of tryptophan. The fluorescence cross section (CF) is calculated and compared with one set of published measured values. We investigate power law (Ady) approximations to CF, where d is diameter, and A and y are parameters adjusted to fit the data, and examine how y varies with d and composition, including the fraction as water. The particle's fluorescence efficiency (QF=CF/geometric-cross-section) can be written for homogeneous particles as QabsRF, where Qabs is the absorption efficiency, and RF, the fraction of the absorbed light emitted as fluorescence, is independent of size and shape. When QF is plotted vs. mid or mi(mr-1)d, where m=mr+imi is the complex refractive index, the plots for different fractions of water in the particle tend to overlap.

  9. Solvation of molecules in superfluid helium enhances the “interaction induced localization” effect

    SciTech Connect (OSTI)

    Walewski, ?ukasz Forbert, Harald; Marx, Dominik

    2014-04-14

    Atomic nuclei become delocalized at low temperatures as a result of quantum effects, whereas they are point-like in the high temperature (classical) limit. For non-interacting nuclei, the delocalization upon lowering the temperature is quantitatively described in terms of the thermal de Broglie wavelength of free particles. Clearly, light non-interacting nuclei – the proton being a prominent one – are much more delocalized at low temperatures compared to heavy nuclei, such as non-interacting oxygen having water in mind. However, strong interactions due to chemical bonding in conjunction with ultra-low temperatures characteristic to superfluid helium nanodroplets change this common picture substantially for nuclei in molecules or clusters. It turns out that protons shared in hydrogen bonds undergo an extreme “interaction induced localization” at temperatures on the order of 1 K, which compresses the protonic spatial distributions to the size of the much heavier donor or acceptor atoms, such as O or Cl nuclei, corresponding to about 0.1% of the volume occupied by a non-interacting proton at the same temperature. Moreover, applying our recently developed hybrid ab initio path integral molecular dynamics/bosonic path integral Monte Carlo quantum simulation technique to a HCl/water cluster, HCl(H{sub 2}O){sub 4}, we find that helium solvation has a significant additional localizing effect of up to about 30% in volume. In particular, the solvent-induced excess localization is the stronger the lesser the given nucleus is already localized in the gas phase reference situation.

  10. Water-soluble carbon nanotube compositions for drug delivery and medicinal applications

    DOE Patents [OSTI]

    Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dmitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jr., Jodie L.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Mason, Kathy A.; Milas, Luka

    2014-07-22

    Compositions comprising a plurality of functionalized carbon nanotubes and at least one type of payload molecule are provided herein. The compositions are soluble in water and PBS in some embodiments. In certain embodiments, the payload molecules are insoluble in water. Methods are described for making the compositions and administering the compositions. An extended release formulation for paclitaxel utilizing functionalized carbon nanotubes is also described.

  11. The influence of field-free orientation on the predissociation dynamics of the NaI molecule

    SciTech Connect (OSTI)

    Zhao, Ze-Yu; Han, Yong-Chang, E-mail: ychan@dlut.edu.cn; Yu, Jie; Cong, Shu-Lin [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China)] [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China)

    2014-01-28

    The orientation and predissociation dynamics of the NaI molecule are studied by using a time-dependent wavepacket method. The NaI molecule is first pre-oriented by a single-cycle pulse (SCP) in terahertz (THz) region and then predissociated by a femtosecond pump pulse. The influence of the molecular field-free orientation on the predissociation dynamics is studied in detail. We calculate the radial and angular distributions, the molecular orientation degrees, and the time-dependent populations for both the ground and excited electronic states. It is found that the pre-orientation affects the angular distributions significantly, and that it has weak influence on the radial distributions. By varying the delay time between the THz SCP and the pump pulse, the angular distribution of the fragments from the predissociation can be manipulated.

  12. Features of the spectral dependences of transmittance of organic semiconductors based on tert-butyl substituted lutetium phthalocyanine molecules

    SciTech Connect (OSTI)

    Belogorokhov, I. A.; Tikhonov, E. V.; Dronov, M. A.; Belogorokhova, L. I.; Ryabchikov, Yu. V.; Tomilova, L. G.; Khokhlov, D. R.

    2011-11-15

    Vibronic properties of organic semiconductors based on tert-butyl substituted phthalocyanine lutetium diphthalocyanine molecules are studied by IR and Raman spectroscopy. It is shown that substitution of several carbon atoms in initial phthalocyanine (Pc) ligands with {sup 13}C isotope atoms causes a spectral shift in the main absorption lines attributed to benzene, isoindol, and peripheral C-H groups. A comparison of spectral characteristics showed that the shift can vary from 3 to 1 cm{sup -1}.

  13. Gas Phase Reactions between Fuel Molecules and Halogens: A Review of the Reaction between Atomic Chlorine and Ammonia

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Steven Ewa Xuefei Tao Jingjing Alecu Mielke Papajak Xu Yu Zheng Annual Report Combustion Energy Frontier Research Center Princeton, NJ Sept. 23, 2010 Truhlar group University of Minnesota Practical methods for including torsional anharmonicity in thermochemical calculations on complex molecules * We proposed a new approximation called the multi-structural method with torsional anharmonicity (MS-T) to calculate conformational-vibrational-rotational partition functions. * It is applicable for

  14. On the influence of singlet oxygen molecules on the speed of flame propagation in methane-air mixture

    SciTech Connect (OSTI)

    Starik, A.M.; Kozlov, V.E.; Titova, N.S.

    2010-02-15

    The effect of the presence of singlet oxygen molecules O{sub 2}(a{sup 1}{delta}{sub g}) in a CH{sub 4}-air mixture on the speed of laminar flame propagation is considered. The known experimental data on the laminar flame speed and ignition delay are used to validate the developed kinetic model involving electronically excited oxygen molecules O{sub 2}(a{sup 1}{delta}{sub g}) and O{sub 2}(b{sup 1}{sigma}{sub g}{sup +}). Numerical simulation shows that the presence of 10% O{sub 2}(a{sup 1}{delta}{sub g}) in molecular oxygen enables to increase significantly (by a factor of 1.7) the speed of flame propagation in a fuel-lean ({phi}=0.45) methane-air mixture. The main reason for such an acceleration of flame propagation is the intensification of chain reactions due to addition of singlet delta oxygen molecules. For a fuel-rich mixture ({phi}=1.9), the growth in the flame speed is significantly smaller and attains a factor of 1.4. (author)

  15. Rotational fluctuation of molecules in quantum clusters. II. Molecular rotation and superfluidity in OCS-doped helium-4 clusters

    SciTech Connect (OSTI)

    Miura, Shinichi [Institute for Molecular Science, 38 Myodaiji, Okazaki 444-8585 (Japan)

    2007-03-21

    In this paper, quantum fluctuations of a carbonyl sulfide molecule in helium-4 clusters are studied as a function of cluster size N in a small-to-large size regime (2{<=}N{<=}64). The molecular rotation of the dopant shows nonmonotonic size dependence in the range of 10{<=}N{<=}20, reflecting the density distribution of the helium atoms around the molecule. The size dependence on the rotational constant shows a plateau for N{>=}20, which is larger than the experimental nanodroplet value. Superfluid response of the doped cluster is found to show remarkable anisotropy especially for N{<=}20. The superfluid fraction regarding the axis perpendicular to the molecular axis shows a steep increase at N=10, giving the significant enhancement of the rotational fluctuation of the molecule. On the other hand, the superfluid fraction regarding the axis parallel to the molecular axis reaches 0.9 at N=5, arising from the bosonic exchange cycles of the helium atoms around the molecular axis. The anisotropy in the superfluid response is found to be the direct consequence of the configurations of the bosonic exchange cycles.

  16. ELECTRON IRRADIATION OF CARBON DISULFIDE-OXYGEN ICES: TOWARD THE FORMATION OF SULFUR-BEARING MOLECULES IN INTERSTELLAR ICES

    SciTech Connect (OSTI)

    Maity, Surajit; Kaiser, Ralf I. [Department of Chemistry, University of Hawai'i at Manoa, Honolulu, HI 96822 (United States)

    2013-08-20

    The formation of sulfur-bearing molecules in interstellar ices was investigated during the irradiation of carbon disulfide (CS{sub 2})-oxygen (O{sub 2}) ices with energetic electrons at 12 K. The irradiation-induced chemical processing of these ices was monitored online and in situ via Fourier transform infrared spectroscopy to probe the newly formed products quantitatively. The sulfur-bearing molecules produced during the irradiation were sulfur dioxide (SO{sub 2}), sulfur trioxide (SO{sub 3}), and carbonyl sulfide (OCS). Formations of carbon dioxide (CO{sub 2}), carbon monoxide (CO), and ozone (O{sub 3}) were observed as well. To fit the temporal evolution of the newly formed products and to elucidate the underlying reaction pathways, kinetic reaction schemes were developed and numerical sets of rate constants were derived. Our studies suggest that carbon disulfide (CS{sub 2}) can be easily transformed to carbonyl sulfide (OCS) via reactions with suprathermal atomic oxygen (O), which can be released from oxygen-containing precursors such as water (H{sub 2}O), carbon dioxide (CO{sub 2}), and/or methanol (CH{sub 3}OH) upon interaction with ionizing radiation. This investigation corroborates that carbonyl sulfide (OCS) and sulfur dioxide (SO{sub 2}) are the dominant sulfur-bearing molecules in interstellar ices.

  17. Drug-resistant TB Nature-inspired Polymers

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Drug-resistant TB Nature-inspired Polymers MRI for Everyone Mesoscale Maneuvers L o s A l a m o s S c i e n c e a n d Te c h n o l o g y M a g a z i n e | Ja n u a r y 2 0 1 5 "Det Syke Barn" (The Sick Child), by Norwegian artist Edvard Munch, shows the artist's sister on her deathbed, stricken with tuberculosis (TB). Commonly called "consumption," TB was often romanticized as the disease of artists because so many of them died from it (Henry David Thoreau, Frédéric Chopin,

  18. Memorandum, AU-1 Clarification on the Drug Testing Custody and Control Form

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    for Department of Energy Contractors | Department of Energy AU-1 Clarification on the Drug Testing Custody and Control Form for Department of Energy Contractors Memorandum, AU-1 Clarification on the Drug Testing Custody and Control Form for Department of Energy Contractors May 20, 2015 Title 10 Code of Federal Regulations part 707 (10 CFR part 707), Workplace Substance Abuse Programs at DOE Sites, applies to DOE contractors and contains the drug testing requirements for their programs.10 CFR

  19. Memorandum, Drug Testing at DOE - September 14, 2007 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Policy, Guidance & Reports » Security » Memorandum, Drug Testing at DOE - September 14, 2007 Memorandum, Drug Testing at DOE - September 14, 2007 As established in his memorandum dated September 14, 2007, the Secretary has determined that applicants for, and holders of, a Department of Energy (DOE) Q or L access authorization (security clearance) will be in Testing Designated Positions (TDP) as specified in DOE Order 3792.3, Drug-Free Federal Workplace Testing Implementation Program, for

  20. Fact Sheet on the Consequences of a Positive Drug Test | Department of

    Energy Savers [EERE]

    Energy Fact Sheet on the Consequences of a Positive Drug Test Fact Sheet on the Consequences of a Positive Drug Test FACT SHEET ON THE CONSEQUENCES OF A POSITIVE DRUG TEST The Secretary has determined that applicants for, and holders of, a DOE "Q" or "L" access authorization (security clearance) will be in Testing Designated Positions (TDP) as specified in DOE Order 3792.3, Drug-Free Federal Workplace Testing Implementation Program, for federal employees, and Title 10

  1. Reporting Prescription Drugs, Over-the-Counter Medications, and Dietary Supplements

    SciTech Connect (OSTI)

    Center for Human Reliability Studies

    2008-02-01

    Overview of types of prescription drugs and over-the-counter medications that must be reported in DOE's Human Reliability Program.

  2. Developing new optical imaging techniques for single particle and molecule tracking in live cells

    SciTech Connect (OSTI)

    Sun, Wei

    2010-12-15

    Differential interference contrast (DIC) microscopy is a far-field as well as wide-field optical imaging technique. Since it is non-invasive and requires no sample staining, DIC microscopy is suitable for tracking the motion of target molecules in live cells without interfering their functions. In addition, high numerical aperture objectives and condensers can be used in DIC microscopy. The depth of focus of DIC is shallow, which gives DIC much better optical sectioning ability than those of phase contrast and dark field microscopies. In this work, DIC was utilized to study dynamic biological processes including endocytosis and intracellular transport in live cells. The suitability of DIC microscopy for single particle tracking in live cells was first demonstrated by using DIC to monitor the entire endocytosis process of one mesoporous silica nanoparticle (MSN) into a live mammalian cell. By taking advantage of the optical sectioning ability of DIC, we recorded the depth profile of the MSN during the endocytosis process. The shape change around the nanoparticle due to the formation of a vesicle was also captured. DIC microscopy was further modified that the sample can be illuminated and imaged at two wavelengths simultaneously. By using the new technique, noble metal nanoparticles with different shapes and sizes were selectively imaged. Among all the examined metal nanoparticles, gold nanoparticles in rod shapes were found to be especially useful. Due to their anisotropic optical properties, gold nanorods showed as diffraction-limited spots with disproportionate bright and dark parts that are strongly dependent on their orientation in the 3D space. Gold nanorods were developed as orientation nanoprobes and were successfully used to report the self-rotation of gliding microtubules on kinesin coated substrates. Gold nanorods were further used to study the rotational motions of cargoes during the endocytosis and intracellular transport processes in live mammalian cells. New rotational information was obtained: (1) during endocytosis, cargoes lost their rotation freedom at the late stage of internalization; (2) cargoes performed train-like motion when they were transported along the microtubule network by motor proteins inside live cells; (3) During the pause stage of fast axonal transport, cargoes were still bound to the microtubule tracks by motor proteins. Total internal reflection fluorescence microscopy (TIRFM) is another non-invasive and far-field optical imaging technique. Because of its near-field illumination mechanism, TIRFM has better axial resolution than epi-fluorescence microscopy and confocal microscopy. In this work, an auto-calibrated, prism type, angle-scanning TIRFM instrument was built. The incident angle can range from subcritical angles to nearly 90{sup o}, with an angle interval less than 0.2{sup o}. The angle precision of the new instrument was demonstrated through the finding of the surface plasmon resonance (SPR) angle of metal film coated glass slide. The new instrument improved significantly the precision in determining the axial position. As a result, the best obtained axial resolution was {approx} 8 nm, which is better than current existing instruments similar in function. The instrument was further modified to function as a pseudo TIRF microscope. The illumination depth can be controlled by changing the incident angle of the excitation laser beam or adjusting the horizontal position of the illumination laser spot on the prism top surface. With the new technique, i.e., variable-illumination-depth pseudo TIRF microscopy, the whole cell body from bottom to top was scanned.

  3. Determining the exact number of dye molecules attached to colloidal CdSe/ZnS quantum dots in Förster resonant energy transfer assemblies

    SciTech Connect (OSTI)

    Kaiser, Uwe; Jimenez de Aberasturi, Dorleta; Vázquez-González, Margarita; Carrillo-Carrion, Carolina; Niebling, Tobias; Parak, Wofgang J.; Heimbrodt, Wolfram

    2015-01-14

    Semiconductor quantum dots functionalized with organic dye molecules are important tools for biological sensor applications. Energy transfer between the quantum dot and the attached dyes can be utilized for sensing. Though important, the determination of the real number of dye molecules attached per quantum dot is rather difficult. In this work, a method will be presented to determine the number of ATTO-590 dye molecules attached to CdSe/ZnS quantum dots based on time resolved spectral analysis. The energy transfer from the excited quantum dot to the attached ATTO-590 dye leads to a reduced lifetime of the quantum dot's excitons. The higher the concentration of dye molecules, the shorter the excitonic lifetime becomes. However, the number of dye molecules attached per quantum dot will vary. Therefore, for correctly explaining the decay of the luminescence upon photoexcitation of the quantum dot, it is necessary to take into account the distribution of the number of dyes attached per quantum dot. A Poisson distribution of the ATTO-590 dye molecules not only leads to excellent agreement between experimental and theoretical decay curves but also additionally yields the average number of dye molecules attached per quantum dot. In this way, the number of dyes per quantum dot can be conveniently determined.

  4. Luminescent systems based on the isolation of conjugated PI systems and edge charge compensation with polar molecules on a charged nanostructured surface

    DOE Patents [OSTI]

    Ivanov, Ilia N.; Puretzky, Alexander A.; Zhao, Bin; Geohegan, David B.; Styers-Barnett, David J.; Hu, Hui

    2014-07-15

    A photoluminescent or electroluminescent system and method of making a non-luminescent nanostructured material into such a luminescent system is presented. The method of preparing the luminescent system, generally, comprises the steps of modifying the surface of a nanostructured material to create isolated regions to act as luminescent centers and to create a charge imbalance on the surface; applying more than one polar molecule to the charged surface of the nanostructured material; and orienting the polar molecules to compensate for the charge imbalance on the surface of the nanostructured material. The compensation of the surface charge imbalance by the polar molecules allows the isolated regions to exhibit luminescence.

  5. Discovery of Small Molecule Isozyme Non-specific Inhibitors of Mammalian Acetyl-CoA Carboxylase 1 and 2

    SciTech Connect (OSTI)

    Corbett, J.; Freeman-Cook, K; Elliott, R; Vajdos, F; Rajamohan, F; Kohls, D; Marr, E; Harwood Jr., H; Esler, W; et al.

    2010-01-01

    Screening Pfizer's compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.

  6. Re-Defining Photovoltaic Efficiency Through Molecule Scale Control. Final Report

    SciTech Connect (OSTI)

    Yardley, James T.

    2015-04-30

    The direct conversion of sunlight into electricity represents one of the most important general means for sustainable energy production. Most modern photovoltaic cells are based on some form of semiconductor material such as silicon that is described by a characteristic energy or ''bandgap''. For solar rays with photon energy lower than the bandgap no absorption occurs and thus no energy is generated. For solar rays with photon energy greater than the bandgap, light may be absorbed to create a pair of electrical charges but only one bandgap of energy is created, leaving any additional energy lost as heat. Thus low bandgap materials can use a great part of the spectrum but can lose much of that energy; high bandgap materials fail to capture much of the spectrum. Thus there is a limit to the efficiency of such a solar cell that turns out to be about 32%. This limit is known as the Shockely-Queisser Limit. The Columbia EFRC program is dedicated to exploration of concepts that in principle can provide for efficiencies beyond this limit. One concept that this EFRC has explored for enhancing the efficiency of solar photovoltaic cells is called “Singlet Fission.” In this concept the absorption of light rays with photon energy at least twice the value of the basic bandgap for the system can produce two pairs of electrical charge carriers. If properly implemented this in principle can significantly reduce the energy lost as heat and give rise to solar cell efficiencies greater than the Shockley-Queisser limit. The problem is that there are virtually no materials that can undergo this process effectively. We have developed new materials that have demonstrated singlet fission efficiencies of almost 100%. We understand how these materials work and we have learned how to design many more systems in the future. So far we have only demonstrated the basic capability for efficient singlet fission. Much more work will be required to design and engineer specific materials that can be used practically in a solar cell system. In addition much work will be required to envision and demonstrate effective device structures that can utilize this concept. However these discoveries do provide the basis for an entirely new set of opportunities for more efficient solar energy generation moving beyond the Shockley-Queisser limit. A second part of the EFRC research program has been to investigate the material and device properties of an entirely new set of materials based on two-dimensional sheets (“ultra-thin”) with thicknesses of only one atom, or a single molecule or just a few atoms. These materials can exhibit conducting, insulating, and semiconducting character and thus they can form the basis for entirely new types of electrical devices. Recent fundamental investigations of these materials, at Columbia and elsewhere, demonstrate clearly that the flow of electrical charges in these systems is fundamentally different from the nature of electrical current flow in conventional materials. This fact presents many possibilities for new photovoltaic device concepts. The EFRC research team has achieved world leadership in the creation and understanding of these materials and in developing the fabrication techniques necessary to create useful devices from them. We have developed the basic fabrication methodology to build structures of these materials into complex device structures, layer by layer. Our EFRC research team has pioneered the synthesis and understanding for graphene, perhaps the simplest of these materials. Graphene can function as a highly transparent conducting material, capable of funneling an electrical charge over reasonable distances without significant energy loss. The EFRC program has also pioneered the development of ultra-thin sheets that function in a way analogous to semiconductor materials as well as sheets that act as electrical insulators. These developments therefore enable the construction of solar cells based on totally different physics from conventional cells. Because the electrons in these ultra-thin sheets interact strongly they will exhibit behaviors quite different from conventional materials with potential to operate at efficiencies beyond the Shockley-Queisser limit. In our EFRC program we have laid out many of the fundamental properties of these materials including the development of unique fabrication techniques. We discovered several new effects that demonstrate strong electron coupling. We have demonstrated the first solar cell that can actually generate electrical power at a high basic efficiency from these fundamentally new materials. There is much more science and technology required before these devices can become practical, but there is also very strong activity worldwide to build electronic devices from these materials, thus providing infrastructure and technical capability to develop these concepts.

  7. DETECTION OF FeCN (X {sup 4}{Delta}{sub i} ) IN IRC+10216: A NEW INTERSTELLAR MOLECULE

    SciTech Connect (OSTI)

    Zack, L. N.; Halfen, D. T.; Ziurys, L. M.

    2011-06-01

    A new interstellar molecule, FeCN (X {sup 4}{Delta}{sub i} ), has been detected in the envelope of the carbon-rich asymptotic giant branch star, IRC+10216. This work is the first definitive detection of an iron-bearing molecule in the interstellar medium and is based on newly measured rest frequencies. Eight successive rotational transitions of this linear free radical in the lowest spin ladder, {Omega} = 7/2, were observed at 2 and 3 mm using the Arizona Radio Observatory (ARO) 12 m telescope. Three transitions appear as single, unblended features at the 1-2 mK level and exhibit characteristic IRC+10216 line profiles; one had previously been observed with the IRAM 30 m telescope. Two other transitions are partially blended, but exhibit distinct emission at the FeCN frequencies. The remaining transitions are either completely contaminated, or are too high in energy. Comparison of the ARO and IRAM data suggests a source size for FeCN of {approx}30'' in IRC+10216, indicating an outer shell distribution, as expected for a free radical. The column density derived for FeCN is N{sub tot} = 8.6 x 10{sup 11} cm{sup -2} with a rotational temperature of T{sub rot} = 21 K. The fractional abundance of this molecule is [FeCN]/[H{sub 2}] {approx} 2-7 x 10{sup -10}-comparable to that of MgCN and KCN in IRC+10216. FeCN is likely formed by gas-phase reactions of Fe{sup +} or neutral iron; the latter has a significant gas-phase abundance in the outer shell. The detection of FeCN is further evidence that metal cyanides/isocyanides dominate the chemistry of refractory elements in IRC+10216.

  8. Resonance enhanced multiphoton and single-photon ionization of molecules and molecular fragments. Final report, May 1993--April 1997

    SciTech Connect (OSTI)

    McKoy, V.

    1998-09-01

    Resonance enhanced multiphoton ionization (REMPI) utilizes pulsed laser radiation to prepare a molecule in an excited state via absorption of one or more photons and to subsequently ionize that level before it decays. A remarkable feature of REMPI is that the very narrow bandwidth of laser radiation makes it possible to select a specific rotational level in the initial (ground) state and to prepare the excited state of interest in a single rotational level. Thus, by suitable choice of the excitation step, it is possible to selectively ionize a species that may be present. The key objective of the effort is to carry out quantitative studies of REMPI of molecules and molecular fragments, as well as of single-photon ionization of these species by coherent VUV radiation, in order to provide a robust description of significant spectral features of interest in related experiments and needed insight into the underlying dynamics of these spectra. A major focus of the effort is joint theoretical and experimental studies of these ion rotational distributions which are being widely studied by the zero-kinetic-energy (ZEKE) technique. This technique, which is based on the detection of photoelectrons resulting from pulsed-field ionization of very high Rydberg states lying just below an ion threshold, makes it possible to obtain cation distributions with subwavenumber resolution. The unprecedented resolution of this ZEKE technique is opening up entirely new vistas in studies of photoionization dynamics, ion spectroscopy, and state-selected ion-molecule reactions. Emerging applications built on the ultra-high resolution of this technique include its use for accurate determination of thermochemically important ionization energies, for characterization of ion rovibrational level structure of large organic molecules, of elemental clusters, and of weakly bound molecular complexes, for probing reactive fragments, and for pump-probe photoelectron studies of wavepacket dynamics. This surge of experimental activity in ultra-high resolution studies of molecular photoelectron spectra continues to raise new theoretical challenges and has provided the stimulus for several of the collaborations with experimental groups in North America and Europe.

  9. Final Report on ``Theories of Strong Electron Correlations in Molecules and Solids’’ - DE-FG02-97ER45640

    SciTech Connect (OSTI)

    Cox, Daniel L

    2013-04-15

    The PI led theoretical studies of correlated hybridization in transition metal complexes, compounds, and molecules, and of electron transport in DNA associated with nanoelectronic conformations attached to gold electrodes and in the presence of DNA repair proteins.

  10. Long-lived charge carrier generation in ordered films of a covalent perylenediimide–diketopyrrolopyrrole–perylenediimide molecule

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hartnett, Patrick E.; Dyar, Scott M.; Margulies, Eric A.; Shoer, Leah E.; Cook, Andrew W.; Eaton, Samuel W.; Marks, Tobin J.; Wasielewski, Michael R.

    2015-07-31

    The photophysics of a covalently linked perylenediimide–diketopyrrolopyrrole–perylenediimide acceptor–donor–acceptor molecule (PDI–DPP–PDI, 1) were investigated and found to be markedly different in solution versus in unannealed and solvent annealed films. Photoexcitation of 1 in toluene results in quantitative charge separation in τ = 3.1 ± 0.2 ps, with charge recombination in τ = 340 ± 10 ps, while in unannealed/disordered films of 1, charge separation occurs in τ < 250 fs, while charge recombination displays a multiexponential decay in ~6 ns. The absence of long-lived, charge separation in the disordered film suggests that few free charge carriers are generated. In contrast, uponmore » CH₂Cl₂ vapor annealing films of 1, grazing-incidence X-ray scattering shows that the molecules form a more ordered structure. Photoexcitation of the ordered films results in initial formation of a spin-correlated radical ion pair (electron–hole pair) as indicated by magnetic field effects on the formation of free charge carriers which live for ~4 μs. This result has significant implications for the design of organic solar cells based on covalent donor–acceptor systems and shows that long-lived, charge-separated states can be achieved by controlling intramolecular charge separation dynamics in well-ordered systems.« less

  11. Evidence for small-molecule-mediated loop stabilization in the structure of the isolated Pin1 WW domain

    SciTech Connect (OSTI)

    Mortenson, David E.; Kreitler, Dale F.; Yun, Hyun Gi; Gellman, Samuel H., E-mail: gellman@chem.wisc.edu; Forest, Katrina T., E-mail: gellman@chem.wisc.edu [University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2013-12-01

    Two structures of a small protein with a defined tertiary fold, the isolated Pin1 WW domain, have been determined via racemic crystallization with small-molecule additives. These additives, which are either racemic or achiral, appear to stabilize a dynamic loop region of the structure. The human Pin1 WW domain is a small autonomously folding protein that has been useful as a model system for biophysical studies of ?-sheet folding. This domain has resisted previous attempts at crystallization for X-ray diffraction studies, perhaps because of intrinsic conformational flexibility that interferes with the formation of a crystal lattice. Here, the crystal structure of the human Pin1 WW domain has been obtained via racemic crystallization in the presence of small-molecule additives. Both enantiomers of a 36-residue variant of the Pin1 WW domain were synthesized chemically, and the l- and d-polypeptides were combined to afford diffracting crystals. The structural data revealed packing interactions of small carboxylic acids, either achiral citrate or a d,l mixture of malic acid, with a mobile loop region of the WW-domain fold. These interactions with solution additives may explain our success in crystallization of this protein racemate. Molecular-dynamics simulations starting from the structure of the Pin1 WW domain suggest that the crystal structure closely resembles the conformation of this domain in solution. The structural data presented here should provide a basis for further studies of this important model system.

  12. Long-lived charge carrier generation in ordered films of a covalent perylenediimide–diketopyrrolopyrrole–perylenediimide molecule

    SciTech Connect (OSTI)

    Hartnett, Patrick E.; Dyar, Scott M.; Margulies, Eric A.; Shoer, Leah E.; Cook, Andrew W.; Eaton, Samuel W.; Marks, Tobin J.; Wasielewski, Michael R.

    2015-07-31

    The photophysics of a covalently linked perylenediimide–diketopyrrolopyrrole–perylenediimide acceptor–donor–acceptor molecule (PDI–DPP–PDI, 1) were investigated and found to be markedly different in solution versus in unannealed and solvent annealed films. Photoexcitation of 1 in toluene results in quantitative charge separation in ? = 3.1 ± 0.2 ps, with charge recombination in ? = 340 ± 10 ps, while in unannealed/disordered films of 1, charge separation occurs in ? < 250 fs, while charge recombination displays a multiexponential decay in ~6 ns. The absence of long-lived, charge separation in the disordered film suggests that few free charge carriers are generated. In contrast, upon CH?Cl? vapor annealing films of 1, grazing-incidence X-ray scattering shows that the molecules form a more ordered structure. Photoexcitation of the ordered films results in initial formation of a spin-correlated radical ion pair (electron–hole pair) as indicated by magnetic field effects on the formation of free charge carriers which live for ~4 ?s. This result has significant implications for the design of organic solar cells based on covalent donor–acceptor systems and shows that long-lived, charge-separated states can be achieved by controlling intramolecular charge separation dynamics in well-ordered systems.

  13. Shape resonances in ground-state diatomic molecules: General trends and the example of RbCs

    SciTech Connect (OSTI)

    Londono, B. E.; Mahecha, J. E.; Luc-Koenig, E.; Crubellier, A.

    2010-07-15

    The presence of shape resonances due to tunneling through the centrifugal barrier modifies strongly the dynamics of cold atom scattering. As shown on the example of the ground and lowest triplet electronic states of the {sup 85}Rb{sup 133}Cs molecule, the crucial parameter is, as usual for cold collisions, the scattering length. A general description of shape resonances of diatomic molecules is given from three simple single channel asymptotic models, whose respective performances are discussed. The first model, which consists of a R{sup -6} potential limited at short range by a repulsive wall, positioned to reproduce the s-wave scattering length, accounts satisfactorily for the main system-independent properties of shape resonances. Introduction in the model of energy- and angular-momentum-dependent nodal lines specific to the inner part of the potential greatly improves its efficiency. When the energy and angular momentum dependence of the nodal lines cannot be deduced from full potential calculations or from experiment, a rough, but universal, estimate of these properties is obtained by extending the R{sup -6} behavior of the potential up to the origin.

  14. Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium

    SciTech Connect (OSTI)

    Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro

    2013-06-01

    Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular side-effects among long term cancer survivors. Vascular modulation warrants nitric oxide (NO) signal transduction, which targets the vascular endothelium. We hypothesize that TC, CP and EP interference with the nitric oxide downstream signaling specifically, could lead to cardiovascular dysfunctions. The results demonstrate that while all three drugs attenuate NO and cyclic guanosine mono-phosphate (cGMP) production in endothelial cells, they caused elevated levels of NO in the plasma and RBC. However, PBMC and platelets did not show any significant changes under treatment. This implies that the drug effects are specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177) localization patterns in endothelial cells were observed following drug treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein was decreased under the treatment of drugs. Altered actin polymerization was also observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed this effect. Incubation with the drugs decreased endothelial cell migration whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally molecular docking studies showed that all three drugs exhibited a strong binding affinity with the catalytic domain of human sGC. In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO–sGC–cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. - Highlights: • NO production is reduced in endothelial cells under breast cancer drug treatment. • Cellular cGMP level is decreased under the treatments of breast cancer drugs. • Breast cancer drugs induce vasoconstriction by interfering with NO pathway. • NO donors, cGMP analogs rescue breast cancer drug induced endothelial dysfunctions.

  15. Synthesis and characterization of polylactide/doxorubicin/magnetic nanoparticles composites for drug delivery

    SciTech Connect (OSTI)

    Mhlanga, Nikiwe; Ray, Suprakas Sinha

    2015-05-22

    Magnetic iron oxide nanoparticles have potential to transform conventional therapeutics, through targeted delivery by external magnetic field modulation. Conventional drug delivery lacks specificity; both normal and infected cells are exposed to toxic drugs. Consequently, the toxicity towards healthy cells leads to detrimental side effects which are formidable. However, iron oxide research in biomedicine has been hindered by their lack of stability. This study reports on the stabilization of iron oxide by polylactide (PLA). Besides affording stable iron oxide, PLA is also good for sustained delivery of the drug. PLA/doxorubicin/magnetic nanoparticles (PLA/DOX/MNPs) spheres were synthesized by solvent evaporation method and DOX anticancer drug was encapsulated. The spheres were characterized using scanning electron microscope, Fourier transform infrared microscope, thermogravimetric analyzer and UV-visible spectroscopy, which ascertained formation of the anticipated spheres and incorporation of DOX. In vitro drug release studies were carried out in both phosphate buffer (pH 7.4) and acetate buffer (pH 4.6) and they showed the same trend in both mediums. Drug release kinetics followed Higuchi model, which proved drug release by diffusion via a diffusion gradient.

  16. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    SciTech Connect (OSTI)

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ? 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ? 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug-induced cholestasis index (DICI) as measure of a drug's cholestatic signature • In vitro findings correlate well with clinical reports on cholestasis.

  17. FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure Data Taken at ALS FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein Structure Data Taken at ALS FDA Approves Drug for Type 2 Diabetes Invented with Aid of Protein Structure Data Taken at ALS Print Friday, 24 May 2013 13:44 In January 2013, the U.S. Food and Drug Administration approved NESINA for the treatment of type 2 diabetes in adults as an adjunct to diet and exercise. NESINA uses a novel mechanism of action to lower blood glucose levels. A dipeptidyl

  18. Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

    SciTech Connect (OSTI)

    Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

    2013-12-01

    The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (? 10 ?M) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential source of cardiac arrhythmias. • 18-Methoxycoronaridine has a lower affinity for cardiac ion channels than ibogaine.

  19. Comparison of light out-coupling enhancements in single-layer blue-phosphorescent organic light emitting diodes using small-molecule or polymer hosts

    SciTech Connect (OSTI)

    Chang, Yung-Ting; Liu, Shun-Wei; Yuan, Chih-Hsien; Lee, Chih-Chien; Ho, Yu-Hsuan; Wei, Pei-Kuen; Chen, Kuan-Yu; Lee, Yi-Ting; Wu, Min-Fei; Chen, Chin-Ti E-mail: chihiwu@cc.ee.ntu.edu.tw; Wu, Chih-I E-mail: chihiwu@cc.ee.ntu.edu.tw

    2013-11-07

    Single-layer blue phosphorescence organic light emitting diodes (OLEDs) with either small-molecule or polymer hosts are fabricated using solution process and the performances of devices with different hosts are investigated. The small-molecule device exhibits luminous efficiency of 14.7?cd/A and maximum power efficiency of 8.39?lm/W, which is the highest among blue phosphorescence OLEDs with single-layer solution process and small molecular hosts. Using the same solution process for all devices, comparison of light out-coupling enhancement, with brightness enhancement film (BEF), between small-molecule and polymer based OLEDs is realized. Due to different dipole orientation and anisotropic refractive index, polymer-based OLEDs would trap less light than small molecule-based OLEDs internally, about 37% better based simulation results. In spite of better electrical and spectroscopic characteristics, including ambipolar characteristics, higher carrier mobility, higher photoluminescence quantum yield, and larger triplet state energy, the overall light out-coupling efficiency of small molecule-based devices is worse than that of polymer-based devices without BEF. However, with BEF for light out-coupling enhancement, the improved ratio in luminous flux and luminous efficiency for small molecule based device is 1.64 and 1.57, respectively, which are significantly better than those of PVK (poly-9-vinylcarbazole) devices. In addition to the theoretical optical simulation, the experimental data also confirm the origins of differential light-outcoupling enhancement. The maximum luminous efficiency and power efficiency are enhanced from 14.7?cd/A and 8.39?lm/W to 23?cd/A and 13.2?lm/W, respectively, with laminated BEF, which are both the highest so far for single-layer solution-process blue phosphorescence OLEDs with small molecule hosts.

  20. EXPERIMENTAL STUDY OF CO{sub 2} FORMATION BY SURFACE REACTIONS OF NON-ENERGETIC OH RADICALS WITH CO MOLECULES

    SciTech Connect (OSTI)

    Oba, Yasuhiro; Watanabe, Naoki; Kouchi, Akira; Hama, Tetsuya; Pirronello, Valerio

    2010-04-01

    Surface reactions between carbon monoxide and non-energetic hydroxyl radicals were carried out at 10 K and 20 K in order to investigate possible reaction pathways to yield carbon dioxide in dense molecular clouds. Hydroxyl radicals, produced by dissociating water molecules in microwave-induced plasma, were cooled down to 100 K prior to the introduction of CO. The abundances of species were monitored in situ using a Fourier transform infrared spectrometer. Formation of CO{sub 2} was clearly observed, even at 10 K, suggesting that reactions of CO with OH proceed with little or no activation barrier. The present results indicate that CO{sub 2} formation, due to reactions between CO and OH, occurs in tandem with H{sub 2}O formation, and this may lead to the formation of CO{sub 2} ice in polar environments, as typically observed in molecular clouds.

  1. Effects of polymethylmethacrylate-transfer residues on the growth of organic semiconductor molecules on chemical vapor deposited graphene

    SciTech Connect (OSTI)

    Kratzer, Markus Teichert, Christian; Bayer, Bernhard C.; Kidambi, Piran R.; Matkovi?, Aleksandar; Gaji?, Radoš; Cabrero-Vilatela, Andrea; Weatherup, Robert S.; Hofmann, Stephan

    2015-03-09

    Scalably grown and transferred graphene is a highly promising material for organic electronic applications, but controlled interfacing of graphene thereby remains a key challenge. Here, we study the growth characteristics of the important organic semiconductor molecule para-hexaphenyl (6P) on chemical vapor deposited graphene that has been transferred with polymethylmethacrylate (PMMA) onto oxidized Si wafer supports. A particular focus is on the influence of PMMA residual contamination, which we systematically reduce by H{sub 2} annealing prior to 6P deposition. We find that 6P grows in a flat-lying needle-type morphology, surprisingly independent of the level of PMMA residue and of graphene defects. Wrinkles in the graphene typically act as preferential nucleation centers. Residual PMMA does however limit the length of the resulting 6P needles by restricting molecular diffusion/attachment. We discuss the implications for organic device fabrication, with particular regard to contamination and defect tolerance.

  2. Electronic transport in biphenyl single-molecule junctions with carbon nanotubes electrodes: The role of molecular conformation and chirality

    SciTech Connect (OSTI)

    Brito Silva, C. A. Jr.; Granhen, E. R. [Pos-Graduacao em Engenharia Eletrica, Universidade Federal do Para, 66075-900 Belem, PA (Brazil); Silva, S. J. S. da; Leal, J. F. P. [Pos-Graduacao em Fisica, Universidade Federal do Para, 66075-110 Belem, PA (Brazil); Del Nero, J. [Departamento de Fisica, Universidade Federal do Para, 66075-110 Belem, PA (Brazil); Divisao de Metrologia de Materiais, Instituto Nacional de Metrologia, Normalizacao e Qualidade Industrial, 25250-020 Duque de Caxias, RJ (Brazil); Instituto de Fisica, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro, RJ (Brazil); Pinheiro, F. A. [Instituto de Fisica, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro, RJ (Brazil)

    2010-08-15

    We investigate, by means of ab initio calculations, electronic transport in molecular junctions composed of a biphenyl molecule attached to metallic carbon nanotubes. We find that the conductance is proportional to cos{sup 2} {theta}, with {theta} the angle between phenyl rings, when the Fermi level of the contacts lies within the frontier molecular orbitals energy gap. This result, which agrees with experiments in biphenyl junctions with nonorganic contacts, suggests that the cos{sup 2} {theta} law has a more general applicability, irrespective of the nature of the electrodes. We calculate the geometrical degree of chirality of the junction, which only depends on the atomic positions, and demonstrate that it is not only proportional to cos{sup 2} {theta} but also is strongly correlated with the current through the system. These results indicate that molecular conformation plays the preponderant role in determining transport properties of biphenyl-carbon nanotubes molecular junctions.

  3. Surface-supported Ag islands stabilized by a quantum size effect: Their interaction with small molecules relevant to ethylene epoxidation

    SciTech Connect (OSTI)

    Shao, Dahai

    2013-05-15

    This dissertation focuses on how QSE-stabilized, surface-supported Ag nanoclusters will interact with ethylene or oxygen. Experiments are performed to determine whether the QSE-mediated Ag islands react differently toward adsorption of ethylene or oxygen, or whether the adsorption of these small molecules will affect the QSE-mediated stability of Ag islands. Studies of the interaction of oxygen with Ag/Si(111)-7×7 were previously reported, but these studies were performed at a low Ag coverage where 3D Ag islands were not formed. So the study of such a system at a higher Ag coverage will be a subject of this work. The interaction of ethylene with Ag/Si(111)-7×7, as well as the interaction of oxygen with Ag/NiAl(110) are also important parts of this study.

  4. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

    SciTech Connect (OSTI)

    Yanagawa, Takashi; Shinozaki, Tetsuya; Watanabe, Hideomi; Saito, Kenichi; Raz, Avraham; Takagishi, Kenji

    2012-04-15

    Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

  5. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect (OSTI)

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  6. ORISE Research Participation Programs at the U.S. Food and Drug

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Administration Research Participation Programs at the U.S. Food and Drug Administration (FDA) Home About FDA About ORISE Current Research Opportunities Site Map Contact ORISE Facebook Twitter Applicants Current Research Participants Sponsors/Mentors How to Do Business with ORISE search Search Welcome to the ORISE Research Participation Programs at the U.S. Food and Drug Administration (FDA). On this site you will find information about these educational and training programs, designed to

  7. Spontaneous Liver Rupture After Treatment With Drug-Eluting Beads (Journal

    Office of Scientific and Technical Information (OSTI)

    Article) | SciTech Connect Spontaneous Liver Rupture After Treatment With Drug-Eluting Beads Citation Details In-Document Search Title: Spontaneous Liver Rupture After Treatment With Drug-Eluting Beads Spontaneous rupture of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) is a rare and life-threatening complication. Pathophysiologic mechanisms are not yet fully known; it is suggested that rupture is preceded by reactive tissue edema and intratumerous

  8. ATHENA desktop human "body" could reduce need for animal drug tests

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ATHENA could reduce need for animal drug tests ATHENA desktop human "body" could reduce need for animal drug tests ATHENA project team is developing four human organ constructs that are based on a significantly miniaturized platform. March 26, 2014 Los Alamos National Laboratory scientist Rashi Iyer leads the ATHENA organ project. Los Alamos National Laboratory scientist Rashi Iyer leads the ATHENA organ project. Contact Nancy Ambrosiano Communications Office (505) 667-0471 Email

  9. Structural and optoelectronic properties of hybrid bulk-heterojunction materials based on conjugated small molecules and mesostructured TiO{sub 2}

    SciTech Connect (OSTI)

    Phan, Hung [Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 (United States); Jahnke, Justin P.; Chmelka, Bradley F. [Department of Chemical Engineering, University of California, Santa Barbara, California 93106 (United States); Nguyen, Thuc-Quyen, E-mail: quyen@chem.ucsb.edu [Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 (United States); Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia)

    2014-06-09

    Improved hybrid bulk-heterojunction materials was fabricated by spin-casting a benchmark conjugated small molecule, namely, 3,6-bis(5-(benzofuran-2-yl)thiophen-2-yl)-2,5-bis(2-ethylhexyl) pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP(TBFu){sub 2}), into mesostructured TiO{sub 2}. Due to both a reduced molecular size and less hydrophobic nature of the conjugated molecules (relative to conjugated polymers), homogeneous and improved infiltration into the mesoporous TiO{sub 2} are achieved without the need for pre-treatment of the TiO{sub 2}. Remarkably, this small molecule can realize loadings of up to 25% of the total pore volume—2.5× the typical loadings achieved for conjugated polymers. The small molecule loading was determined using dynamic secondary ion mass spectroscopy and absorption spectroscopy. Further characterization such as charge transfer and nanoscale conducting atomic force microscopy helps to demonstrate the promise and viability of small molecule donors for hybrid optoelectronic devices.

  10. Dose critical in-vivo detection of anti-cancer drug levels in blood

    DOE Patents [OSTI]

    Miller, Holly H.; Hirschfeld, deceased, Tomas B.

    1991-01-01

    A method and apparatus are disclosed for the in vivo and in vitro detection and measurement of dose critical levels of DNA-binding anti-cancer drug levels in biological fluids. The apparatus comprises a laser based fiber optic sensor (optrode) which utilizes the secondary interactions between the drug and an intercalating fluorochrome bound to a probe DNA, which in turn is attached to the fiber tip at one end thereof. The other end of the optical fiber is attached to an illumination source, detector and recorder. The fluorescence intensity is measured as a function of the drug concentration and its binding constant to the probe DNA. Anticancer drugs which lend themselves to analysis by the use of the method and the optrode of the present invention include doxorubicin, daunorubicin, carminomycin, aclacinomycin, chlorambucil, cyclophosphamide, methotrexate, 5-uracil, arabinosyl cytosine, mitomycin, cis-platinum 11 diamine dichloride procarbazine, vinblastine vincristine and the like. The present method and device are suitable for the continuous monitoring of the levels of these and other anticancer drugs in biological fluids such as blood, serum, urine and the like. The optrode of the instant invention also enables the measurement of the levels of these drugs from a remote location and from multiple samples.

  11. Application of quantitative time-lapse imaging (QTLI) for evaluation of Mrp2-based drug–drug interaction induced by liver metabolites

    SciTech Connect (OSTI)

    Nakanishi, Takeo; Ikenaga, Miho; Fukuda, Hajime; Matsunaga, Norikazu; Tamai, Ikumi

    2012-09-01

    We previously reported a quantitative time-lapse imaging (QTLI)-based analysis method to assess drug–drug interactions (DDI) at multidrug resistance-associated protein 2 (Mrp2) in rat sandwich-cultured hepatocyte (SCH) system, utilizing the fluorescent Mrp2 substrate, 5-(and 6)-carboxy-2?,7?-dichlorofluorescein (CDF). Here, we aimed to examine the feasibility of using QTLI to evaluate DDI involving drug metabolite(s) generated in hepatocytes. We used estradiol (E2) and bilirubin as model compounds; both are not substrates of MRP2, whereas their hepatic metabolites, estradiol-17?-glucuronide (E17G) or bilirubin glucuronides, are known to be its substrates as well as inhibitors. When rat SCHs were pre-exposed with E2, fluorescence of CDF accumulated in bile canaliculi decreased depending upon both the duration of pre-exposure and the concentration of extracellular E2. The decrease corresponded with the increase in intracellular concentration of E17G in hepatocytes. Furthermore, cytotoxicity of vinblastine, a substrate of MRP2, was enhanced in SCHs treated with E2. Similarly, CDF accumulated in bile canaliculi was significantly reduced in rat SCHs pre-exposed with bilirubin. In conclusion, these results suggest that phase II biotransformation of a competitor is reflected in alteration of MRP2-mediated CDF transport detected in QTLI. The QTLI might provide a convenient platform to evaluate transporter-based DDIs involving hepatic metabolites of drug candidates without the need to identify the metabolites. -- Highlights: ? Mrp2-mediated CDF transport is inhibited by E2, but not E17G in vesicle study. ? Both E2 and E17G do not compromise CDF formation from CDFDA in hepatocytes. ? CDF accumulation in bile canaliculi is inhibited by E2 or E17G in QTLI. ? Increasing exposure to E2 decreases CDF accumulation in bile canaliculi in QTLI. ? QTLI is feasible to assess Mrp2-based DDI involving drug metabolite in hepatocytes.

  12. Subunits of highly Fluorescent Protein R-Phycoerythrin as Probes for Cell Imaging and Single-Molecule Detection

    SciTech Connect (OSTI)

    Dragan Isailovic

    2005-12-17

    The purposes of our research were: (1) To characterize subunits of highly fluorescent protein R-Phycoerythrin (R-PE) and check their suitability for single-molecule detection (SMD) and cell imaging, (2) To extend the use of R-PE subunits through design of similar proteins that will be used as probes for microscopy and spectral imaging in a single cell, and (3) To demonstrate a high-throughput spectral imaging method that will rival spectral flow cytometry in the analysis of individual cells. We first demonstrated that R-PE subunits have spectroscopic and structural characteristics that make them suitable for SMD. Subunits were isolated from R-PE by high-performance liquid chromatography (HPLC) and detected as single molecules by total internal reflection fluorescence microscopy (TIRFM). In addition, R-PE subunits and their enzymatic digests were characterized by several separation and detection methods including HPLC, capillary electrophoresis, sodium dodecyl sulfate-polyacrilamide gel electrophoresis (SDS-PAGE) and HPLC-electrospray ionization mass spectrometry (ESI-MS). Favorable absorption and fluorescence of the R-PE subunits and digest peptides originate from phycoerythrobilin (PEB) and phycourobilin (PUB) chromophores that are covalently attached to cysteine residues. High absorption coefficients and strong fluorescence (even under denaturing conditions), broad excitation and emission fluorescence spectra in the visible region of electromagnetic spectrum, and relatively low molecular weights make these molecules suitable for use as fluorescence labels of biomolecules and cells. We further designed fluorescent proteins both in vitro and in vivo (in Escherichia coli) based on the highly specific attachment of PEB chromophore to genetically expressed apo-subunits of R-PE. In one example, apo-alpha and apo-beta R-PE subunits were cloned from red algae Polisiphonia boldii (P. boldii), and expressed in E. coli. Although expressed apo-subunits formed inclusion bodies, fluorescent holo-subunits were formed after incubation of E. coli cells with PEB. Spectroscopic characterization of holo-subunits confirmed that the attachment of PEB chromophore to apo-subunits yielded holo-subunits containing both PEB and urobilin (UB). Fluorescence and differential interference contrast (DIC) microscopy showed polar location of holo-subunit inclusion bodies in E. coli cells. In another example, R-PE apo-subunits were genetically fused to cytoplasmic and periplasmic versions of E. coli maltose binding protein (MBP). Fluorescent proteins formed after attachment of PEB to MBP-subunit fusions in vitro and in vivo contained PEB as the sole chromophore, were soluble, and displayed high orange fluorescence. Fluorescence microscopy showed that fusions are located either throughout cells or at cell poles. In addition, cells containing fluorescent holo-subunits or MBP-subunit fusions were up to ten times brighter than control cells as measured by flow cytometry. Results show that the fluorescent proteins formed after non-enzymatic attachment of PEB to R-PE subunit fusions could be used as reporters of gene expression and protein localization in cells as well as fluorescence labels in flow cytometry. Finally, we demonstrated a high-throughput method able to record emission fluorescence spectra of individual cells containing fluorescent proteins. Upon excitation with a 488 mn argon-ion laser many bacterial cells were imaged by a 20X microscope objective while they moved through a capillary tube. Fluorescence was dispersed by a transmission diffraction grating, and an intensified charge-coupled device (ICCD) camera simultaneously recorded the zero and the first orders of the fluorescence from each cell. Single-cell fluorescence spectra were reconstructed from the distance between zero-order and first-order maxima as well as the length and the pixel intensity distribution of the first-order images. By using this approach, the emission spectrum of E. coli cells expressing green fluorescent protein (GFP) was reconstructed. Also, fluorescence spectra of E

  13. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Underlying the magnetocaloric effect is the idea that magnetism is the result of the ... with the magnetic field, the magnetic entropy (disorder) of the system decreases; if ...

  14. Roaming Molecule Dynamics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... The recent discovery of roaming atom dynamics in the photodissociation of formaldehyde (Arthur Suits, Joel Bowman, and co-workers) led to a study at the CRF to determine whether ...

  15. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Conversely, introducing a magnetic field to certain materials will cause the material to heat up. This happens because, as the spins in such (paramagnetic) materials align with...

  16. Cool Magnetic Molecules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    enhanced magnetic refrigeration at very low temperatures. Not Your Mother's Refrigerator Magnets Some day soon, magnets could do more than clutter up the front of your...

  17. Food and drug reward: overlapping circuits in human obesity and addiction

    SciTech Connect (OSTI)

    Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Baler, R.

    2012-12-01

    Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects - partly mediated by dopamine increases in the limbic system - that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that investigate the role of dopamine in drug addiction and in obesity and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

  18. Mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite composite for targeted drug delivery

    SciTech Connect (OSTI)

    Gu, Lina; He, Xiaomei; Wu, Zhenyu

    2014-11-15

    Highlights: • Mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite composite was synthesized by a simple, efficient and environmental friendly method. • The prepared material had a large surface area, high pore volume, and good magnetic separability. • DOX-loaded Fe{sub 3}O{sub 4}/hydroxyapatite composite exhibited surprising slow drug release behavior and pH-dependent behavior. - Abstract: In this contribution, we introduced a simple, efficient, and green method of preparing a mesoporous Fe{sub 3}O{sub 4}/hydroxyapatite (HA) composite. The as-prepared material had a large surface area, high pore volume, and good magnetic separability, which made it suitable for targeted drug delivery systems. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug release behavior of Fe{sub 3}O{sub 4}/HA composite. The drug release profiles displayed a little burst effect and pH-dependent behavior. The release rate of DOX at pH 5.8 was larger than that at pH 7.4, which could be attributed to DOX protonation in acid medium. In addition, the released DOX concentrations remained at 0.83 and 1.39 ?g/ml at pH 7.4 and 5.8, respectively, which indicated slow, steady, and safe release rates. Therefore, the as-prepared Fe{sub 3}O{sub 4}/hydroxyapatite composite could be an efficient platform for targeted anticancer drug delivery.

  19. A spectroscopic view of internal conversion in a small polyatomic molecule: Sub-Doppler intracavity dye laser spectroscopy of thioformaldehyde

    SciTech Connect (OSTI)

    Clouthier, D.J. (Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055 (United States)); Huang, G.; Merer, A.J. (Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B. C. V6T 1Z1 (Canada))

    1992-08-01

    Intracavity dye laser spectroscopy has been used to obtain sub-Doppler spectra of selected rotational lines in the {ital {tilde A}} {sup 1}{ital A}{sub 2}--{ital {tilde X}} {sup 1}{ital A}{sub 1} 4{sup 1}{sub 0} band of thioformaldehyde with very high resolution and sensitivity. Many of the spectra show extra lines due to perturbations involving high vibrational levels of the ground state. Most of the perturbations observed for {ital K}{sup {prime}}{sub {ital a}} = 0 and 4 are found to correlate well with previous observations of anomalously long single rotational level fluorescence lifetimes and reduced quantum yields (J. Dunlop and D. J. Clouthier, J. Chem. Phys. {bold 93}, 6371 (1990)). {ital S}{sub 1}--{ital S}{sub 0} interaction matrix elements of 0.001--0.006 cm{sup {minus}1} are found for levels involved in simple two level perturbations. The large number of small random perturbations by levels of the ground state is indicative of the first stages of the onset of quantum chaos in a small molecule. Some larger perturbations in the rotational structure are also observed; these are caused by additional local interactions with levels of the nearby triplet state.

  20. Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation

    SciTech Connect (OSTI)

    Li, Ying; Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023 ; Huang, Xiaohua; Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian 116044 ; An, Yue; Ren, Feng; Yang, Zara Zhuyun; Zhu, Hongmei; Zhou, Lei; Department of Anatomy and Developmental Biology, Monash University, Clayton 3800 ; He, Xiaowen; Schachner, Melitta; Xiao, Zhicheng; Department of Anatomy and Developmental Biology, Monash University, Clayton 3800 ; Ma, Keli; Li, Yali; Department of Anatomy, National University of Singapore, Singapore 119078

    2013-10-25

    Highlights: •Down-regulating FUT9 and ST3Gal4 expression blocks L1-induced neuronal differentiation of ESCs. •Up-regulating FUT9 and ST3Gal4 expression in L1-ESCs depends on the activation of PLC?. •L1 promotes ESCs to differentiate into neuron through regulating cell surface glycosylation. -- Abstract: Cell recognition molecule L1 (CD171) plays an important role in neuronal survival, migration, differentiation, neurite outgrowth, myelination, synaptic plasticity and regeneration after injury. Our previous study has demonstrated that overexpressing L1 enhances cell survival and proliferation of mouse embryonic stem cells (ESCs) through promoting the expression of FUT9 and ST3Gal4, which upregulates cell surface sialylation and fucosylation. In the present study, we examined whether sialylation and fucosylation are involved in ESC differentiation through L1 signaling. RNA interference analysis showed that L1 enhanced differentiation of ESCs into neurons through the upregulation of FUT9 and ST3Gal4. Furthermore, blocking the phospholipase C? (PLC?) signaling pathway with either a specific PLC? inhibitor or knockdown PLC? reduced the expression levels of both FUT9 and ST3Gal4 mRNAs and inhibited L1-mediated neuronal differentiation. These results demonstrate that L1 promotes neuronal differentiation from ESCs through the L1-mediated enhancement of FUT9 and ST3Gal4 expression.

  1. Multi-layer Lanczos iteration approach to calculations of vibrational energies and dipole transition intensities for polyatomic molecules

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yu, Hua-Gen

    2015-01-28

    We report a rigorous full dimensional quantum dynamics algorithm, the multi-layer Lanczos method, for computing vibrational energies and dipole transition intensities of polyatomic molecules without any dynamics approximation. The multi-layer Lanczos method is developed by using a few advanced techniques including the guided spectral transform Lanczos method, multi-layer Lanczos iteration approach, recursive residue generation method, and dipole-wavefunction contraction. The quantum molecular Hamiltonian at the total angular momentum J = 0 is represented in a set of orthogonal polyspherical coordinates so that the large amplitude motions of vibrations are naturally described. In particular, the algorithm is general and problem-independent. An applicationmore » is illustrated by calculating the infrared vibrational dipole transition spectrum of CH₄ based on the ab initio T8 potential energy surface of Schwenke and Partridge and the low-order truncated ab initio dipole moment surfaces of Yurchenko and co-workers. A comparison with experiments is made. The algorithm is also applicable for Raman polarizability active spectra.« less

  2. Interaction energy and itinerant ferromagnetism in a strongly interacting Fermi gas in the absence of molecule formation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    He, Lianyi

    2014-11-26

    In this study, we investigate the interaction energy and the possibility of itinerant ferromagnetism in a strongly interacting Fermi gas at zero temperature in the absence of molecule formation. The interaction energy is obtained by summing the perturbative contributions of Galitskii-Feynman type to all orders in the gas parameter. It can be expressed by a simple phase-space integral of an in-medium scattering phase shift. In both three and two dimensions (3D and 2D), the interaction energy shows a maximum before reaching the resonance from the Bose-Einstein condensate side, which provides a possible explanation of the experimental measurements of the interactionmore » energy. This phenomenon can be theoretically explained by the qualitative change of the nature of the binary interaction in the medium. The appearance of an energy maximum has significant effects on the itinerant ferromagnetism. In 3D, the ferromagnetic transition is reentrant and itinerant ferromagnetism exists in a narrow window around the energy maximum. In 2D, the present theoretical approach suggests that itinerant ferromagnetism does not exist, which reflects the fact that the energy maximum becomes much lower than the energy of the fully polarized state.« less

  3. Studies of minute quantities of natural abundance molecules using 2D heteronuclear correlation spectroscopy under 100kHz MAS

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Nishiyama, Y.; Kobayashi, T.; Malon, M.; Singappuli-Arachchige, D.; Slowing, I. I.; Pruski, M.

    2015-02-16

    Two-dimensional 1H{13C} heteronuclear correlation solid-state NMR spectra of naturally abundant solid materials are presented, acquired using the 0.75-mm magic angle spinning (MAS) probe at spinning rates up to 100 kHz. In spite of the miniscule sample volume (290 nL), high-quality HSQC-type spectra of bulk samples as well as surface-bound molecules can be obtained within hours of experimental time. The experiments are compared with those carried out at 40 kHz MAS using a 1.6-mm probe, which offered higher overall sensitivity due to a larger rotor volume. The benefits of ultrafast MAS in such experiments include superior resolution in 1H dimension withoutmore » resorting to 1H–1H homonuclear RF decoupling, easy optimization, and applicability to mass-limited samples. As a result, the HMQC spectra of surface-bound species can be also acquired under 100 kHz MAS, although the dephasing of transverse magnetization has significant effect on the efficiency transfer under MAS alone.« less

  4. Improved production of Br atoms near zero speed by photodissociating laser aligned Br{sub 2} molecules

    SciTech Connect (OSTI)

    Deng, L. Z., E-mail: lzdeng@phy.ecnu.edu.cn; Yin, J. P., E-mail: jpyin@phy.ecnu.edu.cn [State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai 200062 (China)

    2014-10-28

    We theoretically investigated the improvement on the production rate of the decelerated bromine (Br) atoms near zero speed by photodissociating laser aligned Br{sub 2} precursors. Adiabatic alignment of Br{sub 2} precursors exposed to long laser pulses with duration on the order of nanoseconds was investigated by solving the time-dependent Schrödinger equation. The dynamical fragmentation of adiabatically aligned Br{sub 2} precursors was simulated and velocity distribution of the Br atoms produced was analyzed. Our study shows that the larger the degree of the precursor alignment, ?cos{sup 2}???, the higher the production rate of the decelerated Br atoms near zero speed. For Br{sub 2} molecules with an initial rotational temperature of ?1 K, a ?cos{sup 2}??? value of ?0.88 can result in an improvement factor of over ?20 on the production rate of the decelerated Br atoms near zero speed, requiring a laser intensity of only ?1 × 10{sup 12} W/cm{sup 2} for alignment.

  5. Electron correlations and two-photon states in polycyclic aromatic hydrocarbon molecules: A peculiar role of geometry

    SciTech Connect (OSTI)

    Aryanpour, Karan; Shukla, Alok; Mazumdar, Sumit; College of Optical Sciences, University of Arizona, Tucson, Arizona 85721

    2014-03-14

    We present numerical studies of one- and two-photon excited states ordering in a number of polycyclic aromatic hydrocarbon molecules: coronene, hexa-peri-hexabenzocoronene, and circumcoronene, all possessing D{sub 6h} point group symmetry versus ovalene with D{sub 2h} symmetry, within the Pariser-Parr-Pople model of interacting ?-electrons. The calculated energies of the two-photon states as well as their relative two-photon absorption cross-sections within the interacting model are qualitatively different from single-particle descriptions. More remarkably, a peculiar role of molecular geometry is found. The consequence of electron correlations is far stronger for ovalene, where the lowest spin-singlet two-photon state is a quantum superposition of pairs of lowest spin triplet states, as in the linear polyenes. The same is not true for D{sub 6h} group hydrocarbons. Our work indicates significant covalent character, in valence bond language, of the ground state, the lowest spin triplet state and a few of the lowest two-photon states in D{sub 2h} ovalene but not in those with D{sub 6h} symmetry.

  6. Theoretical study of quantum molecular reaction dynamics and of the effects of intense laser radiation on a diatomic molecule

    SciTech Connect (OSTI)

    Dardi, P.S.

    1984-11-01

    Within the very broad field of molecular dynamics, we have concentrated on two simple yet important systems. The systems are simple enough so that they are adequately described with a single Born-Oppenheimer potential energy surface and that the dynamics can be calculated accurately. They are important because they give insight into solving more complicated systems. First we discuss H + H/sub 2/ reactive scattering. We present an exact formalism for atom-diatom reactive scattering which avoids the problem of finding a coordinate system appropriate for both reactants and products. We present computational results for collinear H + H/sub 2/ reactive scattering which agree very well with previous calculations. We also present a coupled channel distorted wave Born approximation for atom-diatom reactive scattering which we show is a first order approximation to our exact formalism. We present coupled channel DWBA results for three dimensional H + H/sub 2/ reactive scattering. The second system is an isolated HF molecule in an intense laser field. Using classical trajectories and quantum dynamics, we look at energy absorbed and transition probabilities as a function of the laser pulse time and also averaged over the pulse time. Calculations are performed for both rotating and nonrotating HF. We examine one and two photon absorption about the fundamental frequency, multiphoton absorption, and overtone absorption. 127 references, 31 figures, 12 tables.

  7. Conservative and dissipative force field for simulation of coarse-grained alkane molecules: A bottom-up approach

    SciTech Connect (OSTI)

    Trément, Sébastien; Rousseau, Bernard, E-mail: bernard.rousseau@u-psud.fr [Laboratoire de Chimie-Physique, UMR 8000 CNRS, Université Paris-Sud, Orsay (France)] [Laboratoire de Chimie-Physique, UMR 8000 CNRS, Université Paris-Sud, Orsay (France); Schnell, Benoît; Petitjean, Laurent; Couty, Marc [Manufacture Française des Pneumatiques MICHELIN, Centre de Ladoux, 23 place des Carmes, 63000 Clermont-Ferrand (France)] [Manufacture Française des Pneumatiques MICHELIN, Centre de Ladoux, 23 place des Carmes, 63000 Clermont-Ferrand (France)

    2014-04-07

    We apply operational procedures available in the literature to the construction of coarse-grained conservative and friction forces for use in dissipative particle dynamics (DPD) simulations. The full procedure rely on a bottom-up approach: large molecular dynamics trajectories of n-pentane and n-decane modeled with an anisotropic united atom model serve as input for the force field generation. As a consequence, the coarse-grained model is expected to reproduce at least semi-quantitatively structural and dynamical properties of the underlying atomistic model. Two different coarse-graining levels are studied, corresponding to five and ten carbon atoms per DPD bead. The influence of the coarse-graining level on the generated force fields contributions, namely, the conservative and the friction part, is discussed. It is shown that the coarse-grained model of n-pentane correctly reproduces self-diffusion and viscosity coefficients of real n-pentane, while the fully coarse-grained model for n-decane at ambient temperature over-predicts diffusion by a factor of 2. However, when the n-pentane coarse-grained model is used as a building block for larger molecule (e.g., n-decane as a two blobs model), a much better agreement with experimental data is obtained, suggesting that the force field constructed is transferable to large macro-molecular systems.

  8. Surface-induced anisotropic orientations of interfacial ethanol molecules at air/sapphire (1-102) and ethanol/sapphire (1-102) interfaces

    SciTech Connect (OSTI)

    Sung, J.; Waychunas, G. A.; Shen, Y. R.

    2011-06-01

    Sum frequency vibrational spectroscopy was used to study the interfacial arrangement of ethanol molecules at the vapor/α-Al{sub 2}O{sub 3} (1{bar 1}02 ) and α-Al{sub 2}O{sub 3} (1{bar 1}02 )/ethanol liquid interfaces. The spectra in the C-H range show that ethanol molecules adsorbed from vapor onto α-Al{sub 2}O{sub 3} (1{bar 1}02 ) surface have a welldefined anisotropic arrangement following the structure of the α-Al{sub 2}O{sub 3} (1{bar 1}02 ) surface. The arrangement can be explained by the formation of two specific hydrogen bonds between the adsorbed ethanol molecule and hydroxyls on the sapphire surface. At the α-Al{sub 2}O{sub 3} (1{bar 1}02 )/ethanol liquid interface, the first ethanol monolayer assumes a similar anisotropic arrangement as in the case of an ethanol monolayer on the dry sapphire surface. The second monolayer has a rather broad orientation distribution that is azimuthally nearly isotropic, but with molecules flipped 180 degrees with respect to those in the first monolayer.

  9. Benchmark atomization energy of ethane : importance of accurate zero-point vibrational energies and diagonal Born-Oppenheimer corrections for a 'simple' organic molecule.

    SciTech Connect (OSTI)

    Karton, A.; Martin, J. M. L.; Ruscic, B.; Chemistry; Weizmann Institute of Science

    2007-06-01

    A benchmark calculation of the atomization energy of the 'simple' organic molecule C2H6 (ethane) has been carried out by means of W4 theory. While the molecule is straightforward in terms of one-particle and n-particle basis set convergence, its large zero-point vibrational energy (and anharmonic correction thereto) and nontrivial diagonal Born-Oppenheimer correction (DBOC) represent interesting challenges. For the W4 set of molecules and C2H6, we show that DBOCs to the total atomization energy are systematically overestimated at the SCF level, and that the correlation correction converges very rapidly with the basis set. Thus, even at the CISD/cc-pVDZ level, useful correlation corrections to the DBOC are obtained. When applying such a correction, overall agreement with experiment was only marginally improved, but a more significant improvement is seen when hydrogen-containing systems are considered in isolation. We conclude that for closed-shell organic molecules, the greatest obstacles to highly accurate computational thermochemistry may not lie in the solution of the clamped-nuclei Schroedinger equation, but rather in the zero-point vibrational energy and the diagonal Born-Oppenheimer correction.

  10. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect (OSTI)

    Tamura, Akitoshi Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  11. Use of supercritical fluid solution expansion processes for drug delivery, particle synthesis, and thin film deposition

    SciTech Connect (OSTI)

    Hybertson, B.M.

    1992-01-01

    Properties of the gases and aerosols resulting from the expansion of supercritical fluid solutions were studied. Film deposition, particle formation, and drug delivery processes using supercritical fluids were developed. Thin films of palladium, copper, aluminum, silver, and silicon dioxide were deposited by a method called supercritical fluid transport-chemical deposition (SFT-CD). In each case, a precursor compound was dissolved in a supercritical fluid and the solution was allowed to expand through a restrictor nozzle into a reaction chamber at subcritical pressure, resulting in the formation of aerosol particles of the precursor. A chemical reaction was induced to occur at the surface of a substrate, resulting in deposition of a thin film. Micron-sized particles of aluminum fluoride and copper oxide were synthesized by a method called supercritical fluid transport-chemical formation of particles (SFT-CFP). The process was similar to that in SFT-CD, but the chemical reactions were induced to occur in the gas phase instead of at a substrate surface, resulting in the formation of fine particles. A new method of pulmonary drug delivery called supercritical fluid drug delivery (SFDD) was conceived and demonstrated. In SFDD a drug compound is dissolved in a supercritical fluid, and the solution is allowed to expand through a restrictor nozzle. The resultant aerosol is directly inhaled by a human or animal subject and the fine drug particles are deposited in the lungs. Menthol, vanillin, camphor, cholesterol, Sudan III, and Oil Blue N were used as model drug compounds for SFDD. Delivery of [alpha]-tocopherol to rat lung tissue was demonstrated, with observed increases of 80-290% above background levels.

  12. SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

    SciTech Connect (OSTI)

    Cormack, R; Ngwa, W; Makrigiorgos, G; Tangutoori, S; Rajiv, K; Sridhar, S

    2014-06-15

    Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities ?,?) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in ?,? or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing ? or ? maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest benefit with drug release over weeks. If in-vivo drug concentrations are not able to approach saturation concentration, durations of days is optimal. DOD 1R21CA16977501; A. David Mazzone Awards Program 2012PD164.

  13. Arranging Prescription Drug Coverage for Extended Stays (Travel or Long-Term Work Assignments) When Outside the United States

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Arranging Prescription Drug Coverage for Extended Stays (Travel or Long-Term Work Assignments) When Outside the United States Planning an extended vacation or working abroad? rx_lanl_override_0311 Maintaining prescription coverage and accessing care for long-term stays abroad What you need to know about override requests and obtaining Rx drugs. Your BCBSNM prescription drug coverage limits override requests to a 90-day supply. Override requests cannot be approved - and are not available -

  14. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; Liang, Wenguang G.; Enée, Emmanuelle; Marechal, Xavier; Charton, Julie; Totobenazara, Jane; Berte, Gonzague; Jahklal, Jouda; et al

    2015-09-23

    Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer’s disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisinglymore » impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.« less

  15. ROVIBRATIONAL LINE LISTS FOR NINE ISOTOPOLOGUES OF THE CO MOLECULE IN THE X {sup 1}?{sup +} GROUND ELECTRONIC STATE

    SciTech Connect (OSTI)

    Li, Gang; Gordon, Iouli E.; Rothman, Laurence S. [Harvard-Smithsonian Center for Astrophysics, Atomic and Molecular Physics Division, Cambridge, MA 02138 (United States); Tan, Yan; Hu, Shui-Ming [Hefei National Laboratory for Sciences at Microscale, University of Science and Technology of China, 230026 Hefei (China); Kassi, Samir; Campargue, Alain [Laboratoire Interdisciplinaire de Physique, CNRS UMR 5588, Université Joseph Fourier de Grenoble, B.P. 87, F-38402 Saint-Martin-d'Hères Cedex (France); Medvedev, Emile S., E-mail: igordon@cfa.harvard.edu [The Institute of Problems of Chemical Physics, Russian Academy of Science, Prospect Akademika Semenova 1, 142432 Chernogolovka (Russian Federation)

    2015-01-01

    Extensive rovibrational line lists were computed for nine isotopologues of the CO molecule, namely, {sup 12}C{sup 16}O, {sup 12}C{sup 17}O, {sup 12}C{sup 18}O, {sup 13}C{sup 16}O, {sup 13}C{sup 17}O, {sup 13}C{sup 18}O, {sup 14}C{sup 16}O, {sup 14}C{sup 17}O, and {sup 14}C{sup 18}O in the ground electronic state with v ? 41, ?v ? 11, and J ? 150. The line intensity and position calculations were carried out using a newly determined piece-wise dipole moment function (DMF) in conjunction with the wavefunctions calculated from an experimentally determined potential energy function from Coxon and Hajigeorgiou. A direct-fit method that simultaneously fits all the reliable experimental rovibrational matrix elements has been used to construct the dipole moment function near equilibrium internuclear distance. In order to extend the amount and quality of input experimental parameters, new Cavity Ring Down Spectroscopy experiments were carried out to enable measurements of the lines in the 4-0 band with low uncertainty as well as the first measurements of lines in the 6-0 band. A new high-level ab initio DMF, derived from a finite field approach has been calculated to cover internuclear distances far from equilibrium. Accurate partition sums have been derived for temperatures up to 9000 K. In addition to air- and self-induced broadening and shift parameters, those induced by CO{sub 2} and H{sub 2} are now provided for planetary applications. A complete set of broadening and shift parameters was calculated based on sophisticated extrapolation of high-quality measured data. The line lists, which follow HITRAN formalism, are provided as supplementary material.

  16. Novel short antibacterial and antifungal peptides with low cytotoxicit...

    Office of Scientific and Technical Information (OSTI)

    From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting ...

  17. A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    De Pillis, L. G.; Radunskaya, A.

    2001-01-01

    We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

  18. A two transition state model for radical-molecule reactions : applications to isomeric branching in the OH-isoprene reaction.

    SciTech Connect (OSTI)

    Greenwald, E. E.; North, S. W.; Georgievskii, Y.; Klippenstein, S. J.; Chemistry; Texas A&M Univ.; SNL

    2007-06-28

    A two transition state model is applied to the prediction of the isomeric branching in the addition of hydroxyl radical to isoprene. The outer transition state is treated with phase space theory fitted to long-range transition state theory calculations on an electrostatic potential energy surface. High-level quantum chemical estimates are applied to the treatment of the inner transition state. A one-dimensional master equation based on an analytic reduction from two-dimensions for a particular statistical assumption about the rotational part of the energy transfer kernel is employed in the calculation of the pressure dependence of the addition process. We find that an accurate treatment of the two separate transition state regions, at the energy and angular momentum resolved level, is essential to the prediction of the temperature dependence of the addition rate. The transition from a dominant outer transition state to a dominant inner transition state is shown to occur at about 275 K, with significant effects from both transition states over the 30-500 K temperature range. Modest adjustments in the ab initio predicted inner saddle point energies yield predictions that are in quantitative agreement with the available high-pressure limit experimental observations and qualitative agreement with those in the falloff regime. The theoretically predicted capture rate is reproduced to within 10% by the expression [1.71 x 10-10(T/298)-2.58 exp(-608.6/RT) + 5.47 x 10-11(T/298)-1.78 exp(-97.3/RT); with R = 1.987 and T in K] cm3 molecule-1 s-1 over the 30-500 K range. A 300 K branching ratio of 0.67:0.02:0.02:0.29 was determined for formation of the four possible OH-isoprene adduct isomers 1, 2, 3, and 4, respectively, and was found to be relatively insensitive to temperature. An Arrhenius activation energy of -0.77 kcal/mol was determined for the high-pressure addition rate constants around 300 K.

  19. Discovery and Characterization of a Cell-Permeable, Small-Molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site

    SciTech Connect (OSTI)

    Yang, Jingsong; Campobasso, Nino; Biju, Mangatt P.; Fisher, Kelly; Pan, Xiao-Qing; Cottom, Josh; Galbraith, Sarah; Ho, Thau; Zhang, Hong; Hong, Xuan; Ward, Paris; Hofmann, Glenn; Siegfried, Brett; Zappacosta, Francesca; Washio, Yoshiaki; Cao, Ping; Qu, Junya; Bertrand, Sophie; Wang, Da-Yuan; Head, Martha S.; Li, Hu; Moores, Sheri; Lai, Zhihong; Johanson, Kyung; Burton, George; Erickson-Miller, Connie; Simpson, Graham; Tummino, Peter; Copeland, Robert A.; Oliff, Allen

    2014-10-02

    c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the {alpha}I helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the {alpha}I helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. DPH represents the first cell-permeable, small-molecule tool compound for c-Abl activation.

  20. Structures of Pseudomonas aeruginosa ?-ketoacyl-(acyl-carrier-protein) synthase II (FabF) and a C164Q mutant provide templates for antibacterial drug discovery and identify a buried potassium ion and a ligand-binding site that is an artefact of the crystal form

    SciTech Connect (OSTI)

    Baum, Bernhard; Lecker, Laura S. M.; Zoltner, Martin; Jaenicke, Elmar; Schnell, Robert; Hunter, William N.; Brenk, Ruth

    2015-07-28

    Three crystal structures of recombinant P. aeruginosa FabF are reported: the apoenzyme, an active-site mutant and a complex with a fragment of a natural product inhibitor. The characterization provides reagents and new information to support antibacterial drug discovery. Bacterial infections remain a serious health concern, in particular causing life-threatening infections of hospitalized and immunocompromised patients. The situation is exacerbated by the rise in antibacterial drug resistance, and new treatments are urgently sought. In this endeavour, accurate structures of molecular targets can support early-stage drug discovery. Here, crystal structures, in three distinct forms, of recombinant Pseudomonas aeruginosa ?-ketoacyl-(acyl-carrier-protein) synthase II (FabF) are presented. This enzyme, which is involved in fatty-acid biosynthesis, has been validated by genetic and chemical means as an antibiotic target in Gram-positive bacteria and represents a potential target in Gram-negative bacteria. The structures of apo FabF, of a C164Q mutant in which the binding site is altered to resemble the substrate-bound state and of a complex with 3-(benzoylamino)-2-hydroxybenzoic acid are reported. This compound mimics aspects of a known natural product inhibitor, platensimycin, and surprisingly was observed binding outside the active site, interacting with a symmetry-related molecule. An unusual feature is a completely buried potassium-binding site that was identified in all three structures. Comparisons suggest that this may represent a conserved structural feature of FabF relevant to fold stability. The new structures provide templates for structure-based ligand design and, together with the protocols and reagents, may underpin a target-based drug-discovery project for urgently needed antibacterials.

  1. Resilience of all-carbon molecules C sub 60 , C sub 70 , and C sub 84 : A surface-scattering time-of-flight investigation

    SciTech Connect (OSTI)

    Beck, R.D.; St. John, P.; Alvarez, M.M.; Diederich, F.; Whetten, R.L. )

    1991-10-17

    Ion beam scattering experiments on the larger carbon molecules (C{sub 60}{sup {plus minus}}, C{sub 70}{sup +} C{sub 80}{sup +}) demonstrate their exceptionally high stability with respect to impact-induced fragmentation processes. The charged molecules are formed by ultraviolet laser desorption of high purity molecular samples into a pulsed helium jet. Extracted ions impact Si(100) or graphite (0001) in a high-resolution ion beam/surface collider with mass time-of-flight and angular analysis. Collisions are highly inelastic processes: a large fraction of the entire perpendicular momentum component is lost, and 60 {plus minus} 20% of the component is either lost or exchanged. No more than 10% of the incident ions are returned, which is attributed to neutralization during the collision event. In contrast to all molecular ions (benzene and naphthalene cations) and cluster (alkali-metal halides), these molecules exhibit no evidence for impact-induced fragmentation, even at impact energies exceeding 200 eV. In the case of C{sub 60}{sup {minus}}, both the intact parent ion and ejected electrons are detected, with the latter becoming dominant above 120 eV impact energy. C{sub 60}{sup +} is found to have an exceptionally low energy threshold for inducing sputtering processes of adsorbed overlayers on graphite. Some of these results may be interpretable in terms of the unique structural-energetic characteristics of the fullerene family. The results are compared to recent computer simulations of the impact event, which predict high resilience for these molecules.

  2. Development of monoclonal antibodies to human microsomal epoxide hydrolase and analysis of “preneoplastic antigen”-like molecules

    SciTech Connect (OSTI)

    Duan, Hongying; Yoshimura, Kazunori; Kobayashi, Nobuharu; Sugiyama, Kazuo; Sawada, Jun-ichi; Saito, Yoshiro; Morisseau, Christophe; Hammock, Bruce D.; Akatsuka, Toshitaka

    2012-04-01

    Microsomal epoxide hydrolase (mEH) is a drug metabolizing enzyme which resides on the endoplasmic reticulum (ER) membrane and catalyzes the hydration of reactive epoxide intermediates that are formed by cytochrome P450s. mEH is also thought to have a role in bile acid transport on the plasma membrane of hepatocytes. It is speculated that efficient execution of such multiple functions is secured by its orientation and association with cytochrome P450 enzymes on the ER membrane and formation of a multiple transport system on the plasma membrane. In certain disease status, mEH loses its association with the membrane and can be detected as distinct antigens in the cytosol of preneoplastic foci of liver (preneoplastic antigen), in the serum in association with hepatitis C virus infection (AN antigen), or in some brain tumors. To analyze the antigenic structures of mEH in physiological and pathological conditions, we developed monoclonal antibodies against different portions of mEH. Five different kinds of antibodies were obtained: three, anti-N-terminal portions; one anti-C-terminal; and one, anti-conformational epitope. By combining these antibodies, we developed antigen detection methods which are specific to either the membrane-bound form or the linearized form of mEH. These methods detected mEH in the culture medium released from a hepatocellular carcinoma cell line and a glioblastoma cell line, which was found to be a multimolecular complex with a unique antigenic structure different from that of the membrane-bound form of mEH. These antibodies and antigen detection methods may be useful to study pathological changes of mEH in various human diseases. -- Highlights: ? Monoclonal antibodies against different portions of mEH were developed. ? They discriminate between the membrane-bound and the linearized forms of mEH. ? We analyze the antigenic structure of the altered form of mEH in tumor cells. ? Preneoplastic antigen is a multimolecular complex of mEH with a unique structure.

  3. Drug Discovery

    ScienceCinema (OSTI)

    Ellingson; Sally

    2014-05-23

    Sally Ellingson harnesses the massive power of supercomputing to seek the next generation of pharmaceuticals

  4. Drug Discovery

    SciTech Connect (OSTI)

    Ellingson; Sally

    2014-05-02

    Sally Ellingson harnesses the massive power of supercomputing to seek the next generation of pharmaceuticals

  5. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    ScienceCinema (OSTI)

    Forte, Trudy

    2011-04-28

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  6. Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

    SciTech Connect (OSTI)

    Valerio, Luis G.; Cross, Kevin P.

    2012-05-01

    Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describe the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ? We characterize a new in silico model to predict mutagenicity of drug impurities. ? The model predicts Salmonella mutagenicity and will be useful for safety assessment. ? We examine toxicity fingerprints and toxicophores of this Ames assay model. ? We compare these attributes to those found in drug impurities known to FDA/CDER. ? We validate the model and find it has a desired predictive performance.

  7. Experimental search for the radiative capture reaction d + d {yields} {sup 4}He + {gamma} from the dd{mu} muonic molecule state J = 1

    SciTech Connect (OSTI)

    Baluev, V. V.; Bogdanova, L. N.; Bom, V. R.; Demin, D. L.; Eijk, C. W. E. van; Filchenkov, V. V.; Grafov, N. N.; Grishechkin, S. K.; Gritsaj, K. I.; Konin, A. D.; Mikhailyukov, K. L.; Rudenko, A. I.; Vinogradov, Yu. I.; Volnykh, V. P.; Yukhimchuk, A. A.; Yukhimchuk, S. A.

    2011-07-15

    A search for the muon-catalyzed fusion reaction d + d {yields} {sup 4}He + {gamma} in the dd{mu} muonic molecule was performed using the experimental installation TRITON with BGO detectors for {gamma}-quanta. A high-pressure target filled with deuterium was exposed to the negative muon beam of the JINR Phasotron to detect {gamma}-quanta with the energy 23.8 MeV. An experimental estimation for the yield of radiative deuteron capture from the dd{mu} state J = 1 was obtained at the level of {eta}{sub {gamma}} {<=} 8 Multiplication-Sign 10{sup -7} per fusion.

  8. Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells

    SciTech Connect (OSTI)

    El-Awady, Raafat A.; Saleh, Ekram M.; Ezz, Marwa; Elsayed, Abeer M.

    2011-09-15

    Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy efficacy in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug's mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide {+-} celecoxib following different incubation schedules were analyzed. We found antagonism between celecoxib and the four drugs in the breast cancer cells MCF7 following all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells. Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosis with damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers. Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule. - Graphical abstract: Display Omitted Highlights: > Celecoxib may enhance effects of anticancer drugs. > Its combination with four drugs was tested in five cancer cell lines. > It antagonized the effects of the four drugs in the breast cancer cell line MCF7. > Doxorubicin's cytotoxic effects were antagonized by celecoxib in four cell lines. > Cell cycle, apoptosis and DNA damage explain the different interactive effects.

  9. P1-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors with Potent Antiviral Activity against Drug-Resistant Viruses

    SciTech Connect (OSTI)

    DeGoey, David A.; Grampovnik, David J.; Chen, Hui-Ju; Flosi, William J.; Klein, Larry L.; Dekhtyar, Tatyana; Stoll, Vincent; Mamo, Mulugeta; Molla, Akhteruzzaman; Kempf, Dale J.

    2013-03-07

    Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported.

  10. The rare crystallographic structure of d(CGCGCG){sub 2}: The natural spermidine molecule bound to the minor groove of left-handed Z-DNA d(CGCGCG){sub 2} at 10 {sup o}C

    SciTech Connect (OSTI)

    Ohishi, Hirofumi . E-mail: ohishi@gly.oups.ac.jp; Tozuka, Yoshitaka; Da-Yang, Zhou; Ishida, Toshimasa; Nakatani, Kazuhiko

    2007-06-22

    Several crystal structure analyses of complexes of synthetic polyamine compounds, including N {sup 1}-(2-(2-aminoethylamino))ethyl)ethane-1,2-diamine PA(222) and N {sup 1}-(2-(2-(2-aminoethylamino)ethylamino)ethyl)ethane-1,2-diamine PA(2222), and left-handed Z-DNA d(CGCGCG){sub 2} have been reported. However, until now, there have been no examples of naturally occurring polyamines bound to the minor groove of the left-handed Z-DNA of d(CGCGCG){sub 2} molecule. We have found that spermidine, a natural polyamine, is connected to the minor groove of left-handed Z-DNA of d(CGCGCG){sub 2} molecule in a crystalline complex grown at 10 {sup o}C. The electron density of the DNA molecule was clear enough to determine that the spermidine was connected in the minor groove of two symmetry related molecules of left-handed Z-DNA d(CGCGCG){sub 2}. This is the first example that a spermidine molecule can form a bridge conformation between two symmetry related molecules of left-handed Z-DNA d(CGCGCG){sub 2} in the minor groove.

  11. State-selective laser photoionization of neutral benzene molecules ejected from keV ion bombarded C{sub 6}H{sub 6}/Ag{l_brace}111{r_brace}

    SciTech Connect (OSTI)

    Meserole, C. A.; Vandeweert, E.; Chatterjee, R.; Chakraborty, B. R.; Garrison, B. J.; Winograd, N.; Postawa, Z.

    1998-12-16

    One-color two-photon ionization spectroscopy was used to probe state-selectively neutral benzene molecules desorbed from a benzene overlayer physisorbed on a Ag{l_brace}111{r_brace} surface upon 8 keV Ar{sup +} bombardment. Time distributions were measured for benzene molecules ejected in the zero level of the molecular ground state and in the first state of the {nu}{sub 6} ' vibration. These distributions are found to show a strong dependence both on the internal energy of the ejected molecules and the degree of coverage of the Ag surface. Up to monolayer coverages, benzene molecules are ejected by direct collisions with Ag particles sputtered from the underlying substrate. Molecules with higher internal energy leave the surface with a distribution shifted towards lower flight times. At multilayer coverages, a second, thermal-like ejection mechanism gains significance. It is suggested that only molecules excited near the benzene-vacuum interface, survive the ejection process without being deexcited.

  12. Ultra-low-temperature reactions of C({sup 3}P{sub 0}) atoms with benzene molecules in helium droplets

    SciTech Connect (OSTI)

    Krasnokutski, Serge A. Huisken, Friedrich

    2014-12-07

    The reaction of carbon atoms with benzene has been investigated in liquid helium droplets at T = 0.37 K. We found an addition of the carbon atom to form an initial intermediate complex followed by a ring opening and the formation of a seven-membered ring. In contrast to a previous gas phase study, the reaction is frozen after these steps and the loss of hydrogen does not occur. A calorimetric technique was applied to monitor the energy balance of the reaction. It was found that more than 267 kJ mol{sup ?1} were released in this reaction. This estimation is in line with quantum chemical calculations of the formation energy of a seven-membered carbon ring. It is suggested that reactions of this kind could be responsible for the low abundance of small polycyclic aromatic hydrocarbon molecules in the interstellar medium. We also found the formation of weakly bonded water-carbon adducts, in which the carbon atom is linked to the oxygen atom of the water molecule with a binding energy of about 33.4 kJ mol{sup ?1}.

  13. Free-complement local-Schrödinger-equation method for solving the Schrödinger equation of atoms and molecules: Basic theories and features

    SciTech Connect (OSTI)

    Nakatsuji, Hiroshi Nakashima, Hiroyuki

    2015-02-28

    The free-complement (FC) method is a general method for solving the Schrödinger equation (SE): The produced wave function has the potentially exact structure as the solution of the Schrödinger equation. The variables included are determined either by using the variational principle (FC-VP) or by imposing the local Schrödinger equations (FC-LSE) at the chosen set of the sampling points. The latter method, referred to as the local Schrödinger equation (LSE) method, is integral-free and therefore applicable to any atom and molecule. The purpose of this paper is to formulate the basic theories of the LSE method and explain their basic features. First, we formulate three variants of the LSE method, the AB, HS, and H{sup T}Q methods, and explain their properties. Then, the natures of the LSE methods are clarified in some detail using the simple examples of the hydrogen atom and the Hooke’s atom. Finally, the ideas obtained in this study are applied to solving the SE of the helium atom highly accurately with the FC-LSE method. The results are very encouraging: we could get the world’s most accurate energy of the helium atom within the sampling-type methodologies, which is comparable to those obtained with the FC-VP method. Thus, the FC-LSE method is an easy and yet a powerful integral-free method for solving the Schrödinger equation of general atoms and molecules.

  14. Protein folding and non-conventional drug design: a primer for nuclear structure physicists

    SciTech Connect (OSTI)

    Broglia, R.A. [Dipartimento di Fisica, Universita di Milano, Via Celoria 16, I-20133 Milan (Italy); INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy); Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Tiana, G.; Provasi, D. [Dipartimento di Fisica, Universita di Milano, Via Celoria 16, I-20133 Milan (Italy); INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy)

    2004-02-27

    Some of the paradigms emerging from the study of the phenomena of phase transitions in finite many-body systems, like e.g. the atomic nucleus can be used at profit to solve the protein folding problem within the framework of simple (although not oversimplified) models. From this solution a paradigm emerges for the design of non-conventional drugs, which inhibit enzymatic action without inducing resistance (mutations). The application of these concepts to the design of an inhibitor to the HIV-protease central in the life cycle of the HIV virus is discussed.

  15. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    SciTech Connect (OSTI)

    Pua, Uei

    2013-06-15

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  16. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    SciTech Connect (OSTI)

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  17. Structure-Based Design of Novel HIV-1 Protease Inhibitors to Combat Drug Resistance

    SciTech Connect (OSTI)

    Ghosh,A.; Sridhar, P.; Leshchenko, S.; Hussain, A.; Li, J.; Kovalevsky, A.; Walters, D.; Wedelind, J.; Grum-Tokars, V.; et al.

    2006-01-01

    Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 Angstroms resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.

  18. Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

    SciTech Connect (OSTI)

    Krokidis, Miltiadis Spiliopoulos, Stavros Katsanos, Konstantinos Sabharwal, Tarun

    2013-04-15

    Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

  19. Local magnetism in the molecule-based metamagnet [Ru2(O2CMe)4]3[Cr(CN)6] probed with implanted muons

    SciTech Connect (OSTI)

    Lancaster, T.; Pratt, F. L.; Blundell, S. J.; Steele, Andrew J.; Baker, Peter J.; Wright, Jack D.; Fishman, Randy Scott; Miller, Joel S.

    2011-01-01

    We present a muon-spin relaxation study of local magnetism in the molecule-based metamagnet [Ru2(O2CMe)4]3[Cr(CN)6]. We observe magnetic order with TN = 33 K, although above 25 K the sublattice spins become less rigid and a degree of static magnetic disorder is observed. The comparison of measurements in applied magnetic field with simulations allows us to understand the origin of the muon response across the metamagnetic transition and to map out the phase diagram of the material. Applied hydrostatic pressures of up to 6 kbar lead to an increase in the local magnetic field along with a complex change in the internal magnetic field distribution.

  20. Visualizing electron delocalization, electron-proton correlations, and the Einstein-Podolsky-Rosen paradox during the photodissociation of a diatomic molecule using two ultrashort laser pulses

    SciTech Connect (OSTI)

    Chelkowski, Szczepan; Bandrauk, Andre D.

    2010-06-15

    We investigate theoretically the dissociative ionization of an H{sub 2}{sup +} molecule using two ultrashort laser (pump-probe) pulses. The pump pulse prepares a dissociating nuclear wave packet on an ungerade surface of H{sub 2}{sup +}. Next, an ultraviolet [or extreme ultraviolet (XUV)] probe pulse ionizes this dissociating state at large (R=20-100 bohr) internuclear distance. We calculate the momenta distributions of protons and photoelectrons which show a (two-slit-like) interference structure. A general, simple interference formula is obtained which depends on the electron and protons momenta, as well as, on the pump-probe delay and also on the durations and polarizations of the laser pulses. This pump-probe scheme reveals a striking quantum delocalization of the electron over two protons which intuitively should be localized on just one of the protons separated by the distance R much larger than the atomic Bohr orbit.

  1. Improving the efficiency of configurational-bias Monte Carlo: A density-guided method for generating bending angle trials for linear and branched molecules

    SciTech Connect (OSTI)

    Sepehri, Aliasghar; Loeffler, Troy D.; Chen, Bin

    2014-08-21

    A new method has been developed to generate bending angle trials to improve the acceptance rate and the speed of configurational-bias Monte Carlo. Whereas traditionally the trial geometries are generated from a uniform distribution, in this method we attempt to use the exact probability density function so that each geometry generated is likely to be accepted. In actual practice, due to the complexity of this probability density function, a numerical representation of this distribution function would be required. This numerical table can be generated a priori from the distribution function. This method has been tested on a united-atom model of alkanes including propane, 2-methylpropane, and 2,2-dimethylpropane, that are good representatives of both linear and branched molecules. It has been shown from these test cases that reasonable approximations can be made especially for the highly branched molecules to reduce drastically the dimensionality and correspondingly the amount of the tabulated data that is needed to be stored. Despite these approximations, the dependencies between the various geometrical variables can be still well considered, as evident from a nearly perfect acceptance rate achieved. For all cases, the bending angles were shown to be sampled correctly by this method with an acceptance rate of at least 96% for 2,2-dimethylpropane to more than 99% for propane. Since only one trial is required to be generated for each bending angle (instead of thousands of trials required by the conventional algorithm), this method can dramatically reduce the simulation time. The profiling results of our Monte Carlo simulation code show that trial generation, which used to be the most time consuming process, is no longer the time dominating component of the simulation.

  2. Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

    SciTech Connect (OSTI)

    Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla

    2012-08-31

    Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

  3. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    SciTech Connect (OSTI)

    Henninger, Christian; Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf ; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard; Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNF?) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline-based anticancer therapy. -- Highlights: ? Normal tissue damage is the therapy limiting side effect of anthracyclines. ? The effect of lovastatin on doxorubicin-induced hepatic damage was analyzed in vivo. ? Lovastatin protects the liver against DNA damage induced by doxorubicin. ? Lovastatin protects against acute and subacute doxorubicin-induced hepatotoxicity. ? Hepatoprotection by lovastatin is independent of the shingolipid metabolism.

  4. Cadmium effect on microsomal drug-metabolizing enzyme activity in rat livers with respect to differences in age and sex

    SciTech Connect (OSTI)

    Ando, M.

    1982-04-01

    The effect of cadmium on the hepatic microsomal drug-metabolizing enzyme system was investigated. Cadmium chloride caused the conversion of cytochrome P-450 to P-420 in rat liver microsomes. The destruction of cytochrome P-450 by cadmium caused the reduction of microsomal drug-metabolizing enzyme activity and prolonged the pentobarbital sleeping time. There is a sex-related difference in the ability of cadmium to inhibit the hepatic drug metabolism in rats: male rats are more sensitive to cadmium than females. The effective period when cadmium prolonged their sleep depended upon the age of rats; older rats were more sensitive to cadmium than younger ones. The maximum increase of sleeping time depended upon the dose level of cadium, and the rate constant of the equations seems to depend upon the age of the animals.

  5. Separations method for polar molecules

    DOE Patents [OSTI]

    Thoma, Steven G.; Bonhomme, Francois R.

    2004-07-27

    A method for separating at least one compound from a liquid mixture containing different compounds where anew crystalline manganese phosphate composition with the formula Mn.sub.3 (PO.sub.4).sub.4.2(H.sub.3 NCH.sub.2 CH.sub.2).sub.3 N.6(H.sub.2 O) is dispersed in the liquid mixture, selectively intercalating one or more compounds into the crystalline structure of the Mn.sub.3 (PO.sub.4).sub.4.2(H.sub.3 NCH.sub.2 CH.sub.2).sub.3 N.6(H.sub.2 O).

  6. Soliton molecules: Experiments and optimization

    SciTech Connect (OSTI)

    Mitschke, Fedor

    2014-10-06

    Stable compound states of several fiber-optic solitons have recently been demonstrated. In the first experiment their shape was approximated, for want of a better description, by a sum of Gaussians. Here we discuss an optimization strategy which helps to find preferable shapes so that the generation of radiative background is reduced.

  7. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    SciTech Connect (OSTI)

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Di Leo, Rosa; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H.W.; Curmi, Paul M.G.; Mabbutt, Bridget C.

    2012-02-15

    The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.

  8. Photoluminescence spectroscopy of YVO{sub 4}:Eu{sup 3+} nanoparticles with aromatic linker molecules: A precursor to biomedical functionalization

    SciTech Connect (OSTI)

    Senty, T. R.; Yalamanchi, M.; Cushing, S. K.; Seehra, M. S.; Bristow, A. D.; Zhang, Y.; Shi, X.

    2014-04-28

    Photoluminescence spectra of YVO{sub 4}:Eu{sup 3+} nanoparticles are presented, with and without the attachment of organic molecules that are proposed for linking to biomolecules. YVO{sub 4}:Eu{sup 3+} nanoparticles with 5% dopant concentration were synthesized via wet chemical synthesis. X-ray diffraction and transmission electron microscopy show the expected wakefieldite structure of tetragonal particles with an average size of 17?nm. Fourier-transform infrared spectroscopy determines that metal-carboxylate coordination is successful in replacing native metal-hydroxyl bonds with three organic linkers, namely, benzoic acid, 3-nitro 4-chloro-benzoic acid, and 3,4-dihydroxybenzoic acid, in separate treatments. UV-excitation photoluminescence spectra show that the position and intensity of the dominant {sup 5}D{sub 0} – {sup 7}F{sub 2} electric-dipole transition at 619?nm are unaffected by the benzoic acid and 3-nitro 4-chloro-benzoic acid treatments. Attachment of 3,4-dihydroxybenzoic acid produces an order-of-magnitude quenching in the photoluminescence, due to the presence of high-frequency vibrational modes in the linker. Ratios of the dominant electric- and magnetic-dipole transitions confirm infrared measurements, which indicate that the bulk crystal of the nanoparticle is unchanged by all three treatments.

  9. The influence of chemisorbed molecules on mass transfer in H-ZSM-5-type zeolites and the location of Broensted acid sites

    SciTech Connect (OSTI)

    Caro, J.; Buelow, M. ); Kaerger, J.; Pfeifer, H. )

    1988-11-01

    Heterogeneous catalysis is one of the most important applications of zeolites. Therefore, various methods have been developed to determine the strength and concentration of Bronsted acid sites in zeolites. Among them, in the last few years, {sup 1}H MAS NMR has become a powerful tool. In addition to the accessibility of the acid sites probed by chemisorption of N-bases, the steric environment of these catalytically active sites is of importance since it imposes constraints on the geometry of the transition state. However, only a few studies have been reported on this topic. Information was obtained from quantum chemical calculations, catalytic experiments, I.R. spectroscopy, and the arrangement of guest molecules. From these investigations it has been concluded that in H-ZSM-5 the channel intersections should be preferential location centers for the Bronsted acid sites. In adsorption technology, in the use of zeolites as shape-selective adsorbents, modification of the molecular sieve properties by chemisorption of nitrogen-containing bases (N-compounds) has become a common technique. The authors have applied the NMR pulsed field gradient technique to study the influence of chemisorbed N-compounds on transport properties of molecular sieves, considering the chemisorbed compounds as transport obstacles.

  10. Including screening in van der Waals corrected density functional theory calculations: The case of atoms and small molecules physisorbed on graphene

    SciTech Connect (OSTI)

    Silvestrelli, Pier Luigi; Ambrosetti, Alberto

    2014-03-28

    The Density Functional Theory (DFT)/van der Waals-Quantum Harmonic Oscillator-Wannier function (vdW-QHO-WF) method, recently developed to include the vdW interactions in approximated DFT by combining the quantum harmonic oscillator model with the maximally localized Wannier function technique, is applied to the cases of atoms and small molecules (X=Ar, CO, H{sub 2}, H{sub 2}O) weakly interacting with benzene and with the ideal planar graphene surface. Comparison is also presented with the results obtained by other DFT vdW-corrected schemes, including PBE+D, vdW-DF, vdW-DF2, rVV10, and by the simpler Local Density Approximation (LDA) and semilocal generalized gradient approximation approaches. While for the X-benzene systems all the considered vdW-corrected schemes perform reasonably well, it turns out that an accurate description of the X-graphene interaction requires a proper treatment of many-body contributions and of short-range screening effects, as demonstrated by adopting an improved version of the DFT/vdW-QHO-WF method. We also comment on the widespread attitude of relying on LDA to get a rough description of weakly interacting systems.

  11. Solid-state chemistry of molecular metal oxide clusters. Multiple, sequential C-H activation processes in the hydrogenation of coordinated cyclooctene. Lattice mobility of small organic molecules

    SciTech Connect (OSTI)

    Siedle, A.R.; Newmark, R.A.; Sahyun, M.R.V.; Lyon, P.A.; Hunt, S.L.; Skarjune, R.P. )

    1989-10-25

    Reaction of solid ((Ph{sub 3}P){sub 2}Ir(C{sub 8}H{sub 12})){sub 3}PW{sub 12}O{sub 40} with D{sub 2} gas produces cyclooctane containing up to 16 deuterium atoms. The c-C{sub 8}D{sub n}H{sub 16-n} isotopomer distribution is analyzed by Poisson statistics and interpreted in terms of C-H activation involving Ir-D-C-H exchange in an intermediate species containing coordinated cyclooctene. The results are compared with those from D{sub 2} reduction of ((Ph{sub 3}P){sub 2}Ir(C{sub 8}H{sub 12}))(PF{sub 6}) in the solid state and in acetone solution, in which cases, an additional exchange process operates. Solid-state {sup 2}H NMR shows that, even at low temperatures, small organic molecules such as cyclooctane and benzene undergo nearly isotropic motion.

  12. Multiple-robot drug delivery strategy through coordinated teams of microswimmers

    SciTech Connect (OSTI)

    Kei Cheang, U; Kim, Min Jun; Lee, Kyoungwoo; Julius, Anak Agung

    2014-08-25

    Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and the strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.

  13. Research Directed at Developing a Classical Theory to Describe Isotope Separation of Polyatomic Molecules Illuminated by Intense Infrared Radiation. Final Report for period May 7, 1979 to September 30, 1979; Extension December 31, 1997

    DOE R&D Accomplishments [OSTI]

    Lamb, W. E. Jr.

    1981-12-01

    This final report describes research on the theory of isotope separation produced by the illumination of polyatomic molecules by intense infrared laser radiation. This process is investigated by treating the molecule, sulfur hexafluoride, as a system of seven classical particles that obey the Newtonian equations of motion. A minicomputer is used to integrate these differential equations. The particles are acted on by interatomic forces, and by the time-dependent electric field of the laser. We have a very satisfactory expression for the interaction of the laser and the molecule which is compatible with infrared absorption and spectroscopic data. The interatomic potential is capable of improvement, and progress on this problem is still being made. We have made several computer runs of the dynamical behavior of the molecule using a reasonably good model for the interatomic force law. For the laser parameters chosen, we find that typically the molecule passes quickly through the resonance region into the quasi-continuum and even well into the real continuum before dissociation actually occurs. When viewed on a display terminal, the motions are exceedingly complex. As an aid to the visualization of the process, we have made a number of 16 mm movies depicting a three-dimensional representation of the motion of the seven particles. These show even more clearly the enormous complexity of the motions, and make clear the desirability of finding ways of characterizing the motion in simple ways without giving all of the numerical detail. One of the ways to do this is to introduce statistical parameters such as a temperature associated with the distribution of kinetic energies of the single particle. We have made such an analysis of our data runs, and have found favorable indications that such methods will prove useful in keeping track of the dynamical histories.

  14. Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines

    SciTech Connect (OSTI)

    Brandon, Esther F.A.; Bosch, Tessa M.; Deenen, Maarten J.; Levink, Rianne; Wal, Everdina van der; Meerveld, Joyce B.M. van; Bijl, Monique; Beijnen, Jos H. |; Schellens, Jan H.M. |; Meijerman, Irma . E-mail: I.Meijerman@pharm.uu.nl

    2006-02-15

    Human cell lines are often used for in vitro biotransformation and transport studies of drugs. In vivo, genetic polymorphisms have been identified in drug-metabolizing enzymes and ABC-drug transporters leading to altered enzyme activity, or a change in the inducibility of these enzymes. These genetic polymorphisms could also influence the outcome of studies using human cell lines. Therefore, the aim of our study was to pharmacogenotype four cell lines frequently used in drug metabolism and transport studies, HepG2, IGROV-1, CaCo-2 and LS180, for genetic polymorphisms in biotransformation enzymes and drug transporters. The results indicate that, despite the presence of some genetic polymorphisms, no real effects influencing the activity of metabolizing enzymes or drug transporters in the investigated cell lines are expected. However, this characterization will be an aid in the interpretation of the results of biotransformation and transport studies using these in vitro cell models.

  15. High open-circuit voltage small-molecule p-DTS(FBTTh 2 )2.ICBA bulk heterojunction solar cells – morphology, excited-state dynamics, and photovoltaic performance

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ko Kyaw, Aung Ko; Gehrig, Dominik; Zhang, Jie; Huang, Ye; Bazan, Guillermo C.; Laquai, Frédéric; Nguyen, Thuc -Quyen

    2014-11-27

    The photovoltaic performance of bulk heterojunction solar cells using the solution-processable small molecule donor 7,7'-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b']dithiophene-2,6-diyl)bis(6-fluoro-4-(5'-hexyl-[2,2'-bithiophene]-5-yl)benzo[c][1,2,5]thiadiazole) (p-DTS(FBTTh2)2 in combination with indene-C60 bis-adduct (ICBA) as an acceptor is systematically optimized by altering the processing conditions. A high open-circuit voltage of 1 V, more than 0.2 V higher than that of a p-DTS(FBTTh2)2:PC70BM blend, is achieved. However, the power conversion efficiency remains around 5% and thus is lower than ~8% previously reported for p-DTS(FBTTh2)2:PC70BM. Transient absorption (TA) pump–probe spectroscopy over a wide spectral (Vis-NIR) and dynamic (fs to μs) range in combination with multivariate curve resolution analysis of the TA data reveals thatmore » generation of free charges is more efficient in the blend with PC70BM as an acceptor. In contrast, blends with ICBA create more coulombically bound interfacial charge transfer (CT) states, which recombine on the sub-nanosecond timescale by geminate recombination. Furthermore, the ns to μs charge carrier dynamics in p-DTS(FBTTh2)2:ICBA blends are only weakly intensity dependent implying a significant contribution of recombination from long-lived CT states and trapped charges, while those in p-DTS(FBTTh2)2:PC70BM decay via an intensity-dependent recombination mechanism indicating that spatially separated (free) charge carriers are observed, which can be extracted as photocurrent from the device.« less

  16. Organo-sulfur molecules enable iron-based battery electrodes to meet the challenges of large-scale electrical energy storage

    SciTech Connect (OSTI)

    Yang, B; Malkhandi, S; Manohar, AK; Prakash, GKS; Narayanan, SR

    2014-07-03

    Rechargeable iron-air and nickel-iron batteries are attractive as sustainable and inexpensive solutions for large-scale electrical energy storage because of the global abundance and eco-friendliness of iron, and the robustness of iron-based batteries to extended cycling. Despite these advantages, the commercial use of iron-based batteries has been limited by their low charging efficiency. This limitation arises from the iron electrodes evolving hydrogen extensively during charging. The total suppression of hydrogen evolution has been a significant challenge. We have found that organo-sulfur compounds with various structural motifs (linear and cyclic thiols, dithiols, thioethers and aromatic thiols) when added in milli-molar concentration to the aqueous alkaline electrolyte, reduce the hydrogen evolution rate by 90%. These organo-sulfur compounds form strongly adsorbed layers on the iron electrode and block the electrochemical process of hydrogen evolution. The charge-transfer resistance and double-layer capacitance of the iron/electrolyte interface confirm that the extent of suppression of hydrogen evolution depends on the degree of surface coverage and the molecular structure of the organo-sulfur compound. An unanticipated electrochemical effect of the adsorption of organo-sulfur molecules is "de-passivation" that allows the iron electrode to be discharged at high current values. The strongly adsorbed organo-sulfur compounds were also found to resist electro-oxidation even at the positive electrode potentials at which oxygen evolution can occur. Through testing on practical rechargeable battery electrodes we have verified the substantial improvements to the efficiency during charging and the increased capability to discharge at high rates. We expect these performance advances to enable the design of efficient, inexpensive and eco-friendly iron-based batteries for large-scale electrical energy storage.

  17. Interaction between S100P and the anti-allergy drug cromolyn

    SciTech Connect (OSTI)

    Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin

    2014-11-21

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

  18. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    SciTech Connect (OSTI)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M. . E-mail: meike.mevissen@vpi.unibe.ch

    2006-11-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 {mu}g/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)

  19. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

    SciTech Connect (OSTI)

    Kostadinova, Radina; Boess, Franziska; Suter, Laura; Weiser, Thomas; Singer, Thomas; Roth, Adrian

    2013-04-01

    Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ? 3D liver co-cultures maintain liver specific functions for up to three months. ? Activities of Cytochrome P450s remain drug- inducible accross three months. ? 3D liver co-cultures recapitulate drug-induced liver toxicity observed in vivo. ? 3D liver co-cultures can detect species-specific drug toxicity observed in vivo. ? This in vitro model may improve assessment of human relevance of preclinical findings.

  20. Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

    SciTech Connect (OSTI)

    Vickers, Alison E.M.; Heale, Jason; Sinclair, John R.; Morris, Stephen; Rowe, Josh M.; Fisher, Robyn L.

    2012-04-01

    Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ? 10 ?M MMI. Thyroid from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (? 15–84 ?M), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (? 10 ?M) and PTU (100 ?M). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ? 2-fold) and only at higher MMI concentrations (? 1500 ?M, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ? Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ? TPO inhibition by MMI or PTU altered hormone synthesis and release genes. ? Rat thyroid was more sensitive to the drug effects than human tissue.

  1. Multi-functional ultrathin PdxCu1-x and Pt~PdxCu1-x one-dimensional nanowire motifs for various small molecule oxidation reactions

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Liu, Haiqing; Wong, Stanislaus S.; Adzic, Radoslav R.

    2015-11-18

    Developing novel electrocatalysts for small molecule oxidation processes, including formic acid oxidation (FAOR), methanol oxidation reaction (MOR), and ethanol oxidation reaction (EOR), denoting the key anodic reactions for their respective fuel cell configurations, is a significant and relevant theme of recent efforts in the field. Herein, in this report, we demonstrated a concerted effort to couple and combine the benefits of small size, anisotropic morphology, and tunable chemical composition in order to devise a novel “family” of functional architectures. In particular, we have fabricated not only ultrathin 1-D Pd1–xCux alloys but also Pt-coated Pd1–xCux (i.e., Pt~Pd1–xCux; herein the ~ indicatesmore » an intimate association, but not necessarily actual bond formation, between the inner bimetallic core and the Pt outer shell) core–shell hierarchical nanostructures with readily tunable chemical compositions by utilizing a facile, surfactant-based, wet chemical synthesis coupled with a Cu underpotential deposition technique. Our main finding is that our series of as-prepared nanowires are functionally flexible. More precisely, we demonstrate that various examples within this “family” of structural motifs can be tailored for exceptional activity with all 3 of these important electrocatalytic reactions. In particular, we note that our series of Pd1–xCux nanowires all exhibit enhanced FAOR activities as compared with not only analogous Pd ultrathin nanowires but also commercial Pt and Pd standards, with Pd9Cu representing the “optimal” composition. Moreover, our group of Pt~Pd1–xCux nanowires consistently outperformed not only commercial Pt NPs but also ultrathin Pt nanowires by several fold orders of magnitude for both the MOR and EOR reactions in alkaline media. As a result, the variation of the MOR and EOR performance with the chemical composition of our ultrathin Pt~Pd1–xCux nanowires was also discussed.« less

  2. Synthesis and Exploratory Catalysis of 3d Metals: Group-Transfer Reactions, and the Activation and Functionalization of Small Molecules Including Greenhouse Gases

    SciTech Connect (OSTI)

    Mindiola, Daniel J.

    2014-05-07

    Our work over the past three years has resulted in the development of electron rich and low-coordinate vanadium fragments, molecular nitrides of vanadium and parent imide systems of titanium, and the synthesis of phosphorus containing molecules of the 3d transition metal series. Likewise, with financial support from BES Division in DOE (DE-FG02-07ER15893), we now completed the full characterization of the first single molecular magnet (SMM) of Fe(III). We demonstrated that this monomeric form of Fe(III) has an unusual slow relaxation of the magnetization under zero applied field. To make matters more interesting, this system also undergoes a rare example of an intermediate to high-spin transition (an S = 3/2 to S = 5/2 transition). In 2010 we reported the synthesis of the first neutral and low-coordinate vanadium complexes having the terminal nitride functionality. We have now completed a full study to understand formation of the nitride ligand from the metastable azide precursor, and have also explored the reactivity of the nitride ligand in the context of incomplete and complete N-atom transfer. During the 2010-2013 period we also discovered a facile approach to assemble low-coordinate and low-valent vanadium(II) complexes and exploit their multielectron chemistry ranging from 1-3 electrons. Consequently, we can now access 3d ligand frameworks such as cyclo-P3 (and its corresponding radical anion), nitride radical anions and cations, low-coordinate vanadium oxo’s, and the first example of a vanadium thionitrosyl complex. A cis-divacant iron(IV) imido having some ligand centered radical has been also discovered, and we are in the process of elucidating its electronic structure (in particular the sign of zero field splitting and the origin of its magnitude), bonding and reactivity. We have also revisited some paramagnetic and classic metallocene compounds with S >1/2 ground states in order to understand their reactivity patterns and electronic structure. Lastly, we are completing the synthesis and characterization of a titanium nitride anion and formation of the first example of boryl and aluminyl imido titanium complexes.

  3. CARS study of linewidths of the Q-branch of hydrogen molecules at high temperatures in a pulsed high-pressure H{sub 2}-O{sub 2} combustion chamber

    SciTech Connect (OSTI)

    Vereschagin, Konstantin A; Vereschagin, Alexey K; Smirnov, Valery V; Stelmakh, O M; Fabelinskii, V I; Clauss, W; Klimenko, D N; Oschwald, M

    2005-03-31

    The results of measurements of individual line widths of the Q-branch of a hydrogen molecule and the corresponding coefficients of broadening caused by collisions with water molecules at T = 2700 K in a repetitively pulsed high-pressure (50-200 atm) hydrogen-oxygen combustion chamber are presented. CARS spectra of individual Q{sub 1}-Q{sub 7} hydrogen lines, pressure pulses, and the broadband CARS spectra of the entire Q-branch of hydrogen are recorded simultaneously during a single laser pulse. The shape of line profiles was analysed using a Fabry-Perot interferometer. The temperature in the volume being probed was determined from the 'broadband' CARS spectra. The entire body of the experimental results gives information on the spectral linewidths, temperature and pressure in the combustion chamber during CARS probing. (laser applications and other topics in quantum electronics)

  4. Subtle Changes in Peptide Conformation Profoundly Affect Recognition of the Non-Classical MHC Class I Molecule HLA-E by the CD94?NKG2 Natural Killer Cell Receptors

    SciTech Connect (OSTI)

    Hoare, Hilary L.; Sullivan, Lucy C.; Clements, Craig S.; Ely, Lauren K.; Beddoe, Travis; Henderson, Kate N.; Lin, Jie; Reid, Hugh H.; Brooks, Andrew G.; Rossjohn, Jamie

    2008-03-31

    Human leukocyte antigen (HLA)-E is a non-classical major histocompatibility complex class I molecule that binds peptides derived from the leader sequences of other HLA class I molecules. Natural killer cell recognition of these HLA-E molecules, via the CD94-NKG2 natural killer family, represents a central innate mechanism for monitoring major histocompatibility complex expression levels within a cell. The leader sequence-derived peptides bound to HLA-E exhibit very limited polymorphism, yet subtle differences affect the recognition of HLA-E by the CD94-NKG2 receptors. To better understand the basis for this peptide-specific recognition, we determined the structure of HLA-E in complex with two leader peptides, namely, HLA-Cw*07 (VMAPRALLL), which is poorly recognised by CD94-NKG2 receptors, and HLA-G*01 (VMAPRTLFL), a high-affinity ligand of CD94-NKG2 receptors. A comparison of these structures, both of which were determined to 2.5-{angstrom} resolution, revealed that allotypic variations in the bound leader sequences do not result in conformational changes in the HLA-E heavy chain, although subtle changes in the conformation of the peptide within the binding groove of HLA-E were evident. Accordingly, our data indicate that the CD94-NKG2 receptors interact with HLA-E in a manner that maximises the ability of the receptors to discriminate between subtle changes in both the sequence and conformation of peptides bound to HLA-E.

  5. Using Clinical Data, Hypothesis Generation Tools and PubMed Trends to Discover the Association between Diabetic Retinopathy and Antihypertensive Drugs

    SciTech Connect (OSTI)

    Senter, Katherine G; Sukumar, Sreenivas R; Patton, Robert M; Chaum, Ed

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of blindness and common complication of diabetes. Many diabetic patients take antihypertensive drugs to prevent cardiovascular problems, but these drugs may have unintended consequences on eyesight. Six common classes of antihypertensive drug are angiotensin converting enzyme (ACE) inhibitors, alpha blockers, angiotensin receptor blockers (ARBs), -blockers, calcium channel blockers, and diuretics. Analysis of medical history data might indicate which of these drugs provide safe blood pressure control, and a literature review is often used to guide such analyses. Beyond manual reading of relevant publications, we sought to identify quantitative trends in literature from the biomedical database PubMed to compare with quantitative trends in the clinical data. By recording and analyzing PubMed search results, we found wide variation in the prevalence of each antihypertensive drug in DR literature. Drug classes developed more recently such as ACE inhibitors and ARBs were most prevalent. We also identified instances of change-over-time in publication patterns. We then compared these literature trends to a dataset of 500 diabetic patients from the UT Hamilton Eye Institute. Data for each patient included class of antihypertensive drug, presence and severity of DR. Graphical comparison revealed that older drug classes such as diuretics, calcium channel blockers, and -blockers were much more prevalent in the clinical data than in the DR and antihypertensive literature. Finally, quantitative analysis of the dataset revealed that patients taking -blockers were statistically more likely to have DR than patients taking other medications, controlling for presence of hypertension and year of diabetes onset. This finding was concerning given the prevalence of -blockers in the clinical data. We determined that clinical use of -blockers should be minimized in diabetic patients to prevent retinal damage.

  6. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    SciTech Connect (OSTI)

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2012-10-01

    Although estrogen receptor (ER)? agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ER? have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ER? agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ER?-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ER? in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ? Liver injury induced by drugs or chemicals was investigated in mice. ? Liver injury was suppressed by pretreatment with tamoxifen in female mice. ? Mmd2, whose function was unknown, could be a candidate gene for liver protection. ? Tamoxifen up-regulated Mmd2 mRNA expression via ER?.

  7. A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities

    SciTech Connect (OSTI)

    Valencia, Antoni; Prous, Josep; Mora, Oscar; Sadrieh, Nakissa; Valerio, Luis G.

    2013-12-15

    As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry?, a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90% was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 ± 1% sensitivity, 81 ± 1% specificity, 83 ± 1% concordance and 79 ± 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. - Highlights: • A new in silico QSAR model to predict Ames mutagenicity is described. • The model is extensively validated with chemicals from the FDA and the public domain. • Validation tests show desirable high sensitivity and high negative predictivity. • The model predicted 14 reportedly difficult to predict drug impurities with accuracy. • The model is suitable to support risk evaluation of potentially mutagenic compounds.

  8. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    SciTech Connect (OSTI)

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.

  9. Prediction of multi-drug resistance transporters using a novel sequence analysis method [version 2; referees: 2 approved

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    McDermott, Jason E.; Bruillard, Paul; Overall, Christopher C.; Gosink, Luke; Lindemann, Stephen R.

    2015-03-09

    There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequencesimilarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first showmore » that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.« less

  10. Approaches to efficiently estimate solvation and explicit water energetics in ligand binding: the use of WaterMap [WaterMap and Its Implementation in Drug Discovery

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yang, Yue; Wong, Sergio E.; Lightstone, Felice C.

    2012-09-08

    Solvents play quite an important role in most chemical and biological processes. It is widely accepted that the presence of water or other solvents in many chemical reactions can result in much lower energy barrier. In enzymatic catalysis, water mediated reaction pathways have been observed in various studies. In addition, different conformation flexibility and hydrogen bond patterns have been discovered for cyclic peptides in the presence of membrane and water, further illustrating the impact of solvent in biological activities such like membrane penetration. moreover, as will be discussed later in this review, water also plays a critical role in host-guestmore » chemistry and thus is essential to drug design. As such, it is not surprising that accounting for solvents is critical in drug discovery since drugs must modulate biological systems.« less

  11. Opportunities for Russian Nuclear Weapons Institute developing computer-aided design programs for pharmaceutical drug discovery. Final report

    SciTech Connect (OSTI)

    1996-09-23

    The goal of this study is to determine whether physicists at the Russian Nuclear Weapons Institute can profitably service the need for computer aided drug design (CADD) programs. The Russian physicists` primary competitive advantage is their ability to write particularly efficient code able to work with limited computing power; a history of working with very large, complex modeling systems; an extensive knowledge of physics and mathematics, and price competitiveness. Their primary competitive disadvantage is their lack of biology, and cultural and geographic issues. The first phase of the study focused on defining the competitive landscape, primarily through interviews with and literature searches on the key providers of CADD software. The second phase focused on users of CADD technology to determine deficiencies in the current product offerings, to understand what product they most desired, and to define the potential demand for such a product.

  12. Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

    SciTech Connect (OSTI)

    Atienzar, Franck A.; Novik, Eric I.; Gerets, Helga H.; Parekh, Amit; Delatour, Claude; Cardenas, Alvaro; MacDonald, James; Yarmush, Martin L.; Dhalluin, Stéphane

    2014-02-15

    Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes.

  13. Accurate determination of pair potentials for a C{sub w}H{sub x}N{sub y}O{sub z} system of molecules: A semiempirical method

    SciTech Connect (OSTI)

    Thiel, M. van; Ree, F.H.; Haselman, L.C.

    1995-03-01

    Statistical mechanical chemical equilibrium calculations of the properties of high-pressure high-temperature reactive C,H,N,O mixtures are made to derive an accurate self-consistent set of inter-molecular potentials for the product molecules. Previous theoretical efforts to predict such properties relied in part on Corresponding States theory and shock wave data of argon. More recent high-pressure Hugoniot measurements on a number of elements and molecules allow more accurate determination of the potentials of these materials, and explicit inclusion of additional dissociation products. The present discussion briefly reviews the previous analysis and the method used to produce a self-consistent set of potentials from shock data on N{sub 2}, O{sub 2}, H{sub 2}, NO, an N{sub 2} + O{sub 2} mixture, carbon, CO{sub 2}, and CO, as well as some simple explosive product mixtures from detonation of hexanitrobenzene, PETN, and a mixture of hydrazine nitrate, hydrazine and water. The results are tested using the data from an HMX explosive formulations. The effect of the non-equilibrium nature of carbon clusters is estimated using data for TNT as a standard to determine a nonequilibrium equation of state for carbon. The resulting parameter set is used in a survey of 27 explosives. For the subset that contains no fluorine or two-phase carbon effects the rms deviation from experimental detonation velocity is 1.2%.

  14. A density functional tight binding/force field approach to the interaction of molecules with rare gas clusters: Application to (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters

    SciTech Connect (OSTI)

    Iftner, Christophe; Simon, Aude; Korchagina, Kseniia; Rapacioli, Mathias; Spiegelman, Fernand

    2014-01-21

    We propose in the present paper a SCC-DFTB/FF (Self-Consistent-Charge Density Functional based Tight Binding/Force-Field) scheme adapted to the investigation of molecules trapped in rare gas environments. With respect to usual FF descriptions, the model involves the interaction of quantum electrons in a molecule with rare gas atoms in an anisotropic scheme. It includes polarization and dispersion contributions and can be used for both neutral and charged species. Parameters for this model are determined for hydrocarbon-argon complexes and the model is validated for small hydrocarbons. With the future aim of studying polycyclic aromatic hydrocarbons in Ar matrices, extensive benchmark calculations are performed on (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters against DFT and CCSD(T) calculations for the smaller sizes, and more generally against other experimental and theoretical data. Results on the structures and energetics (isomer ordering and energy separation, cohesion energy per Ar atom) are presented in detail for n = 1–8, 13, 20, 27, and 30, for both neutrals and cations. We confirm that the clustering of Ar atoms leads to a monotonous decrease of the ionization potential of benzene for n ? 20, in line with previous experimental and FF data.

  15. Influence of the support of CoMo sulfide catalysts and of the addition of potassium and platinum on the catalytic performances for the hydrodeoxygenation of carbonyl, carboxyl, and guaiacol-type molecules

    SciTech Connect (OSTI)

    Centeno, A.; Laurent, E.; Delmon, B. [Universite Catholique de Louvain, Louvain-la-Neuve (Belgium)] [Universite Catholique de Louvain, Louvain-la-Neuve (Belgium)

    1995-07-01

    The present work corresponds to part of a program aimed at upgrading oil obtained by pyrolysis of biomass by hydrotreatment (hydrodeoxygenation HDO). CoMo sulfide catalysts, nonsupported, supported on different supports (alumina, carbon, silica), or modified by K or Pt, were used. The authors used a model reacting mixture containing compounds representative of the molecules that must react to permit a primary stabilisation of the pyrolytic oil: 4-methy lacetophenone (4-MA), diethylsebacate (DES), and guaiacol (GUA). In the reaction of the carbonyl group of the 4-MA it is shown that no important role is played by any acid-base mechanism; dispersion determines the activity. Acidity of the support influences the formation of active sites for decarboxylation and hydrogenation of the carboxyl group of DES. It was confirmed that guaiacol-type molecules lead to coking reactions. The role of acidity in the mechanism of these reactions is confirmed, but the modifications made in the catalysts in this work are still not sufficient to control coke deposition. The catalysts supported on carbon lead to the direct elimination of the methoxyl group of the guaiacol. Carbon, on the whole, seems to be a promising support. This work suggests that appropriate modifications of the hydrotreating catalysts can lead to a more effective process for stabilisation of the bio-oils by reaction with hydrogen. 55 refs., 3 figs., 5 tabs.

  16. Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Echevarria, Desarae; Gutfraind, Alexander; Boodram, Basmattee; Major, Marian; Del Valle, Sara; Cotler, Scott J.; Dahari, Harel

    2015-08-21

    New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

  17. Three-dimensional structures of Plasmodium falciparum spermidine synthase with bound inhibitors suggest new strategies for drug design

    SciTech Connect (OSTI)

    Sprenger, Janina; Svensson, Bo; Hålander, Jenny; Carey, Jannette; Persson, Lo; Al-Karadaghi, Salam

    2015-03-01

    In this work, X-ray crystallography was used to examine ligand complexes of spermidine synthase from the malaria parasite Plasmodium falciparum (PfSpdS). The enzymes of the polyamine-biosynthesis pathway have been proposed to be promising drug targets in the treatment of malaria. Spermidine synthase (SpdS; putrescine aminopropyltransferase) catalyzes the transfer of the aminopropyl moiety from decarboxylated S-adenosylmethionine to putrescine, leading to the formation of spermidine and 5?-methylthioadenosine (MTA). In this work, X-ray crystallography was used to examine ligand complexes of SpdS from the malaria parasite Plasmodium falciparum (PfSpdS). Five crystal structures were determined of PfSpdS in complex with MTA and the substrate putrescine, with MTA and spermidine, which was obtained as a result of the enzymatic reaction taking place within the crystals, with dcAdoMet and the inhibitor 4-methylaniline, with MTA and 4-aminomethylaniline, and with a compound predicted in earlier in silico screening to bind to the active site of the enzyme, benzimidazol-(2-yl)pentan-1-amine (BIPA). In contrast to the other inhibitors tested, the complex with BIPA was obtained without any ligand bound to the dcAdoMet-binding site of the enzyme. The complexes with the aniline compounds and BIPA revealed a new mode of ligand binding to PfSpdS. The observed binding mode of the ligands, and the interplay between the two substrate-binding sites and the flexible gatekeeper loop, can be used in the design of new approaches in the search for new inhibitors of SpdS.

  18. High-throughput behavioral phenotyping of drug and alcohol susceptibility traits in the expanded panel of BXD recombinant inbred strains

    SciTech Connect (OSTI)

    Philip, Vivek M [ORNL; Ansah, T [University of Tennessee Health Science Center, Memphis; Blaha, C, [University of Tennessee Health Science Center, Memphis; Cook, Melloni N. [University of Memphis; Hamre, Kristin M. [University of Tennessee Health Science Center, Memphis; Lariviere, William R [University of Pittsburgh; Matthews, Douglas B [Baylor University; Goldowitz, Daniel [University of British Columbia, Vancouver; Chesler, Elissa J [ORNL

    2010-01-01

    Genetic reference populations, particularly the BXD recombinant inbred strains, are a valuable resource for the discovery of the bio-molecular substrates and genetic drivers responsible for trait variation and co- ariation. This approach can be profitably applied in the analysis of susceptibility and mechanisms of drug and alcohol use disorders for which many predisposing behaviors may predict occurrence and manifestation of increased preference for these substances. Many of these traits are modeled by common mouse behavioral assays, facilitating the detection of patterns and sources of genetic co-regulation of predisposing phenotypes and substance consumption. Members of the Tennessee Mouse Genome Consortium have obtained behavioral phenotype data from 260 measures related to multiple behavioral assays across several domains: self-administration, response to, and withdrawal from cocaine, MDMA, morphine and alcohol; novelty seeking; behavioral despair and related neurological phenomena; pain sensitivity; stress sensitivity; anxiety; hyperactivity; and sleep/wake cycles. All traits have been measured in both sexes and the recently expanded panel of 69 additional BXD recombinant inbred strains (N=69). Sex differences and heritability estimates were obtained for each trait, and a comparison of early (N = 32) and recent BXD RI lines was performed. Primary data is publicly available for heritability, sex difference and genetic analyses using www.GeneNetwork.org. These analyses include QTL detection and genetic analysis of gene expression. Stored results from these analyses are available at http://ontologicaldiscovery.org for comparison to other genomic analysis results. Together with the results of related studies, these data form a public resource for integrative systems genetic analysis of neurobehavioral traits.

  19. Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance

    SciTech Connect (OSTI)

    Mickisch, G.H.; Merlino, G.T.; Galski, H.; Gottesman, M.M.; Pastan, I. )

    1991-01-15

    The development of preclinical models for the rapid testing of agents that circumvent multidrug resistance in cancer is a high priority of research on drug resistance. A common form of multidrug resistance in human cancer results from expression of the MDR1 gene, which encodes a M{sub r} 170,000 glycoprotein that functions as a plasma membrane energy-dependent multidrug efflux pump. The authors have engineered transgenic mice that express this multidrug transporter in their bone marrow and demonstrated that these animals are resistant to leukopenia by a panel of anticancer drugs including anthracyclines, vinca alkaloids, etoposide, taxol, and actinomycin D. Differential leukocyte counts indicate that both neutrophils and lympohcytes are pretected. Drugs such as cisplatin, methotrexate, and 5-fluorouracil, which are not handled by the multidrug transporter, produce bone marrow suppression in both normal and transgenic mice. The resistance conferred by the MDR1 gene can be circumvented in a dose-dependent manner by simultaneous administration of agents previously shown to be inhibitors of the multidrug transporter in vitro, including verapamil isomers, quinidine, and quinine. They conclude that MDR1-transgenic mice provide a rapid and reliable system to determine the bioactivity of agents that reverse multidrug resistance in animals.

  20. Parallel Molecular Dynamics Program for Molecules

    Energy Science and Technology Software Center (OSTI)

    1995-03-07

    ParBond is a parallel classical molecular dynamics code that models bonded molecular systems, typically of an organic nature. It uses classical force fields for both non-bonded Coulombic and Van der Waals interactions and for 2-, 3-, and 4-body bonded (bond, angle, dihedral, and improper) interactions. It integrates Newton''s equation of motion for the molecular system and evaluates various thermodynamical properties of the system as it progresses.