National Library of Energy BETA

Sample records for disease orthopedic maternity

  1. In-vivo orthopedic implant diagnostic device for sensing load, wear, and infection

    DOE Patents [OSTI]

    Evans, III, Boyd McCutchen; Thundat, Thomas G.; Komistek, Richard D.; Dennis, Douglas A.; Mahfouz, Mohamed

    2006-08-29

    A device for providing in vivo diagnostics of loads, wear, and infection in orthopedic implants having at least one load sensor associated with the implant, at least one temperature sensor associated with the implant, at least one vibration sensor associated with the implant, and at least one signal processing device operatively coupled with the sensors. The signal processing device is operable to receive the output signal from the sensors and transmit a signal corresponding with the output signal.

  2. SU-E-I-63: Quantitative Evaluation of the Effects of Orthopedic Metal Artifact Reduction (OMAR) Software On CT Images for Radiotherapy Simulation

    SciTech Connect (OSTI)

    Jani, S [Sharp Memorial Hospital, San Diego, CA (United States)

    2014-06-01

    Purpose: CT simulation for patients with metal implants can often be challenging due to artifacts that obscure tumor/target delineation and normal organ definition. Our objective was to evaluate the effectiveness of Orthopedic Metal Artifact Reduction (OMAR), a commercially available software, in reducing metal-induced artifacts and its effect on computed dose during treatment planning. Methods: CT images of water surrounding metallic cylindrical rods made of aluminum, copper and iron were studied in terms of Hounsfield Units (HU) spread. Metal-induced artifacts were characterized in terms of HU/Volume Histogram (HVH) using the Pinnacle treatment planning system. Effects of OMAR on enhancing our ability to delineate organs on CT and subsequent dose computation were examined in nine (9) patients with hip implants and two (2) patients with breast tissue expanders. Results: Our study characterized water at 1000 HU with a standard deviation (SD) of about 20 HU. The HVHs allowed us to evaluate how the presence of metal changed the HU spread. For example, introducing a 2.54 cm diameter copper rod in water increased the SD in HU of the surrounding water from 20 to 209, representing an increase in artifacts. Subsequent use of OMAR brought the SD down to 78. Aluminum produced least artifacts whereas Iron showed largest amount of artifacts. In general, an increase in kVp and mA during CT scanning showed better effectiveness of OMAR in reducing artifacts. Our dose analysis showed that some isodose contours shifted by several mm with OMAR but infrequently and were nonsignificant in planning process. Computed volumes of various dose levels showed <2% change. Conclusions: In our experience, OMAR software greatly reduced the metal-induced CT artifacts for the majority of patients with implants, thereby improving our ability to delineate tumor and surrounding organs. OMAR had a clinically negligible effect on computed dose within tissues. Partially funded by unrestricted educational grant from Philips.

  3. Preconception maternal polychlorinated biphenyl concentrations and the secondary sex ratio

    SciTech Connect (OSTI)

    Taylor, Kira C. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States); Department of Epidemiology, 1518 Clifton Road, NE Atlanta, GA 30322 (United States); Jackson, Leila W. [Department of Epidemiology and Biostatistics, WG37, Case Western Reserve University School of Medicine, 10900 Euclid Avenue Cleveland, OH 44106-4945 (United States); Lynch, Courtney D. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States); Kostyniak, Paul J. [Toxicology Research Center, 134 Cary Hall, University at Buffalo, State of New York, 3434 Main St., Buffalo, NY 14214-3000 (United States); Buck Louis, Germaine M. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States)]. E-mail: louisg@mail.nih.gov

    2007-01-15

    The secondary sex ratio is the ratio of male to female live births and historically has ranged from 102 to 106 males to 100 females. Temporal declines have been reported in many countries prompting authors to hypothesize an environmental etiology. Blood specimens were obtained from 99 women aged 24-34 prior to attempting pregnancy and quantified for 76 polychlorinated biphenyl (PCB) congeners using dual column gas chromatography with electron capture detection. Women were prospectively followed until pregnancy or 12 cycles of trying. The odds of a male birth for three PCB groupings (total, estrogenic, anti-estrogenic) controlling for maternal characteristics were estimated using logistic regression. Among the 50 women with live births and PCB data, 26 female and 24 male infants were born (ratio 0.92). After adjusting for age and body mass index, odds of a male birth were elevated among women in the second (OR=1.29) and third (OR=1.48) tertiles of estrogenic PCBs; odds (OR=0.70) were reduced among women in the highest tertile of anti-estrogenic PCBs. All confidence intervals included one. The direction of the odds ratios in this preliminary study varied by PCB groupings, supporting the need to study specific PCB patterns when assessing environmental influences on the secondary sex ratio.

  4. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect (OSTI)

    Ronco, Ana Maria, E-mail: amronco@inta.cl [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Saez, Daniel [Faculty of Veterinary Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Hirsch, Sandra [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile); Zepeda, Ramiro [Faculty of Medicine, University of Chile, Casilla 138-11, Santiago (Chile); Llanos, Miguel N. [Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago (Chile)

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  5. Beryllium disease

    SciTech Connect (OSTI)

    Not Available

    1991-12-20

    After two workers at the nuclear weapons plant at Oak Ridge National Laboratory in Tennessee were diagnosed earlier this year with chronic beryllium disease (CBD), a rare and sometimes fatal scarring of the lungs, the Department of Energy ordered up a 4-year probe. Now, part of that probe has begun - tests conducted by the Oak Ridge Associated Universities' Center for Epidemiological Research measuring beryllium sensitivity in 3,000 people who've been exposed to the metal's dust since Manhattan Project managers opened the Y-12 plant at Oak Ridge in 1943. Currently, 119 Y-12 employees process beryllium, which has a number of industrial uses, including rocket heat shields and nuclear weapon and electrical components. The disease often takes 20 to 25 years to develop, and the stricken employees haven't worked with beryllium for years. There is no cure for CBD, estimated to strike 2% of people exposed to the metal. Anti-inflammatory steroids alleviate such symptoms as a dry cough, weight loss, and fatigue. Like other lung-fibrosis diseases that are linked to lung cancer, some people suspect CBD might cause some lung cancer. While difficult to diagnose, about 900 cases of CBD have been reported since a Beryllium Case Registry was established in 1952. The Department of Energy (DOE) estimates that about 10,000 DOE employees and 800,000 people in private industry have worked with beryllium.

  6. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

    SciTech Connect (OSTI)

    Patterson, Tucker A.; Twaddle, Nathan C.; Roegge, Cindy S.; Callicott, Ralph J.; Fisher, Jeffrey W.; Doerge, Daniel R.

    2013-02-15

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 ?g/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 ?g/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ? Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ? Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ? BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ? BPA levels in monkey placenta are similar to other metabolically active tissues. ? Some published human cord blood data for BPA are inconsistent with these measurements.

  7. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    SciTech Connect (OSTI)

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  8. Interim Chronic Beryllium Disease

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

    1999-12-08

    Establishes Departmental expectations for addressing chronic beryllium disease throughout the Department until a Departmental rule on beryllium is promulgated. This Notice was replaced by final rule 10 CFR Part 850, Chronic Beryllium Disease Prevention Program, published December 8, 1999.

  9. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

    SciTech Connect (OSTI)

    Shorey, Lyndsey E.; Madeen, Erin P.; Atwell, Lauren L.; Ho, Emily; Löhr, Christiane V.; Pereira, Clifford B.; Dashwood, Roderick H.; Williams, David E.

    2013-07-01

    Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C for transplacental protection. • SFN is abundant in cruciferous vegetables and may enhance risk in this model. • SFN and its mercapturic acid metabolites were measurable in neonatal plasma.

  10. Adventures in Infectious Diseases

    ScienceCinema (OSTI)

    Fisher-Hoch, Susan [University of Texas School of Public Health

    2014-06-25

    Dr. Susan Fisher-Hoch, Virologist and Epidemiologist, will discuss her research and travels associated with viral hemorrhagic fevers. From the Ebola outbreak in Reston, Virginia to outbreaks of Crimean Congo Hemorrhagic Fever in South Africa, Senegal, and Saudi Arabia, Dr. Fisher-Hoch has studied and tracked the pathophysiology of these viral diseases. These studies have led her from the Center for Disease Control in the United States, to Lyon, France where she was instrumental in designing, constructing, and rendering operational a laboratory capable of containing some of the world's most dangerous diseases.

  11. Gas bubble disease: introduction

    SciTech Connect (OSTI)

    Fickeisen, D.H.; Schneider, M.J.; Wedemeyer, G.A.

    1980-11-01

    In 1970, gas bubble disease was identified as a serious problem affecting salmonids in the Columbia and Snake river systems. The source of supersaturation was entrainment of air into water spilling over hydroelectric dams. Regional research projects focusing on tolerance bioassays were immediately implemented. Since then, the scope of gas bubble disease research has broadened to include problems in other aquatic systems, with other species. Emphasis has shifted from defining tolerance limits in bioassay systems to exploring behavioral and physiological aspects. Various methods of degasifying supersaturated water have been developed.

  12. Using Wikipedia to forecast diseases

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

    Using Wikipedia to forecast diseases Using Wikipedia to forecast diseases Scientists can now monitor and forecast diseases around the globe more effectively by analyzing views of Wikipedia articles. November 13, 2014 Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Contact Nancy Ambrosiano Communications Office (505)

  13. Etiology of Early Lifestage Diseases, Project 84-44, 1985 Final Report.

    SciTech Connect (OSTI)

    Sauter, R.W.

    1986-10-01

    Each year hatcheries experience loss of eggs, fry and fingerlings due to a group of poorly defined diseases called White Spot and Coagulated Yolk. Samples of maternal blood and ovarian fluid (coelomic fluid), as well as unfertilized eggs, were collected at spawning and subsequently tested for the presence of bacteria. Our tests reveal that there is a wide range in mortality rates experienced by the progeny of different brood salmon. Microbiologic tests revealed that these eggs contained a variety of both Gram positive and Gram negative bacteria within their yolk and that the fluids from the females who produced these lots were contaminated with a variety of bacteria. In contrast the eggs and maternal fluids from the six egg lots which experienced the lowest mortalities did not contain high numbers of Gram positive bacteria and contributed only 5% of the total mortalities observed within the 30 egg lots tested. From the 60 egg lots tested over two brood years we have isolated 18 different bacterial genera containing 32 different species from within the yolk surface sterilized, unfertilized eggs. Our tests suggest that Aeromonas hydrophila, Pseudomonas (3 species) Staphylococcus aureus, Vibrio sp., Corynebacterium hoffmanii, Listeria sp. and Bacillus sp. when detected within the yolk of eggs sampled from egg lots prior to fertilization will be associated with higher than normal mortality rates when the remainder of the egg lots containing these bacteria are incubated and reared. 36 refs., 16 figs.

  14. Interactive effects of maternal and environmental exposure to coal combustion wastes decrease survival of larval southern toads (Bufo terrestris)

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

    Interactive effects of maternal and environmental exposure to coal combustion wastes decrease survival of larval southern toads (Bufo terrestris) Brian S. Metts a, * , Kurt A. Buhlmann a , David E. Scott a , Tracey D. Tuberville a , William A. Hopkins b a Savannah River Ecology Laboratory, Drawer E, Aiken, SC 29802, USA b Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, VA 24061, USA a r t i c l e i n f o Article history: Received 16 August 2011 Received in revised form

  15. Early detection of contagious diseases

    DOE Patents [OSTI]

    Colston, Jr., Billy W. (San Ramon, CA); Milanovich, Fred P. (Lafayette, CA); Estacio, Pedro (Mission San Jose, CA); Chang, John (Walnut Creek, CA)

    2011-08-09

    This invention provides an electronic proximity apparatus and a surveillance method using such an apparatus for alerting individuals that are exposed to a contagious disease. When a person becomes symptomatic and is diagnosed as positive for a given contagious agent, individuals that have recently maintained a threshold proximity with respect to an infected individual are notified and advised to seek immediate medial care. Treatment of individuals in the very early phases of infection (pre-symptomatic) significantly reduces contagiousness of the infected population first exposed to the contagious disease, thus preventing spread of the disease throughout the general population.

  16. Patching genes to fight disease

    SciTech Connect (OSTI)

    Holzman, D.

    1990-09-03

    The National Institutes of Health has approved the first gene therapy experiments, one of which will try to cure cancer by bolstering the immune system. The applications of such therapy are limited, but the potential aid to people with genetic diseases is great.

  17. Etiology of gas bubble disease

    SciTech Connect (OSTI)

    Bouck, G.R.

    1980-11-01

    Gas bubble disease is a noninfectious, physically induced process caused by uncompensated hyperbaric pressure of total dissolved gases. When pressure compensation is inadequate, dissolved gases may form emboli (in blood) and emphysema (in tissues). The resulting abnormal physical presence of gases can block blood vessels (hemostasis) or tear tissues, and may result in death. Population mortality is generally skewed, in that the median time to death occurs well before the average time to death. Judged from mortality curves, three stages occur in gas bubble disease: (1) a period of gas pressure equilibrium, nonlethal cavitation, and increasing morbidity; (2) a period of rapid and heavy mortality; and (3) a period of protracted survival, despite lesions, and dysfunction that eventually terminates in total mortality. Safe limits for gas supersaturation depend on species tolerance and on factors that differ among hatcheries and rivers, between continuous and intermittent exposures, and across ranges of temperature and salinity.

  18. New Clues in Predicting Alzheimer's Disease

    ScienceCinema (OSTI)

    Jagust, William

    2013-05-29

    Theres a new clue in the search to identify the harbingers of Alzheimers disease. More info: http://newscenter.lbl.gov/feature-stories/2008/12/16/predict-alzheimers-disease/

  19. Protein Instability and Lou Gehrig's Disease

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

    Protein Instability and Lou Gehrig's Disease Protein Instability and Lou Gehrig's Disease Print Wednesday, 25 March 2015 00:00 A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called

  20. Therapeutic target for protozoal diseases

    DOE Patents [OSTI]

    Rathore, Dharmendar (Blacksburg, VA); Jani, Dewal (Blacksburg, VA); Nagarkatti, Rana (Blacksburg, VA)

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  1. Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

    SciTech Connect (OSTI)

    Ribes, Diana; Fuentes, Silvia; Torrente, Margarita; Colomina, M. Teresa [Department of Psychology and Research Center for Behavioral Assessment (CRAMC), 'Rovira i Virgili' University, Sescelades Campus, 43007 Tarragona, Catalonia (Spain); Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, 'Rovira i Virgili' University, Sant Llorenc 21, 43201 Reus, Catalonia (Spain); Domingo, Jose L., E-mail: joseluis.domingo@urv.ca [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, 'Rovira i Virgili' University, Sant Llorenc 21, 43201 Reus, Catalonia (Spain)

    2010-02-15

    Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

  2. Protein Instability and Lou Gehrig's Disease

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

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  3. Protein Instability and Lou Gehrig's Disease

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

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  4. Protein Instability and Lou Gehrig's Disease

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

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  5. Protein Instability and Lou Gehrig's Disease

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

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  6. Protein Instability and Lou Gehrig's Disease

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

    called superoxide dismutase (SOD). The study provides evidence that those proteins linked to more severe forms of the disease are less stable structurally and more prone to...

  7. Influence of metal(loid) bioaccumulation and maternal transfer on embryo-larval development in fish exposed to a major coal ash spill

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

    Greeley, Jr., Mark Stephen; Adams, S. Marshall; Elmore, Logan R.; McCracken, Mary Kitty

    2016-01-03

    In December 2008, an earthen retaining wall at the Tennessee Valley Authority (TVA) Kingston Fossil Fuel Plant failed and released 4.1 million m3 of coal ash to rivers flowing into Watts Bar Reservoir in east Tennessee, United States (U.S.). As part of a comprehensive effort to evaluate the risks to aquatic resources from this spill – the largest in U.S. history – we compared bioaccumulation and maternal transfer of selenium (Se), arsenic (As), and mercury (Hg) in adult redear sunfish (Lepomis macrolophus), collected two years after the spill from both coal-ash exposed and non-exposed areas of the Emory and Clinchmore » Rivers, with the success of embryo-larval development in their offspring. Whole body and ovary concentrations of Se in female sunfish at three study sites downstream of the spill were significantly elevated (site means = 4.9–5.3 and 6.7–9.0 mg/kg d.w. whole body and ovary concentrations, respectively) compared with concentrations in fish from reference sites upstream of the spill site (2.2–3.2 mg/kg d.w. for whole bodies and 3.6–4.8 mg/kg d.w. for ovaries). However, Se concentrations in coal ash-exposed areas remain below proposed U.S. Environmental Protection Agency (USEPA) criteria for the protection of aquatic life. Site-to-site variation in fish concentrations of As and Hg were not well-correlated with ash-exposure, reflecting the multiple sources of these metal(loid)s in the affected watersheds. In 7-day laboratory tests of embryos and larvae derived from in vitro crosses of eggs and sperm from these field-collected sunfish, fertilization success, hatching success, embryo-larval survival, and incidences of developmental abnormalities did not differ significantly between ash-exposed and non-exposed fish. Furthermore, these developmental endpoints were not correlated with whole body or ovary concentrations of Se, As, or Hg in the maternal fish, or with fish size, ovary weight, or gonadal-somatic indices. Furthermore, results from this and related studies associated with the Kingston coal ash spill are consistent with proposed USEPA fish-based water quality criteria for Se, and to date continue to suggest that long-term exposures to sediment containing residual ash may not present a significant chronic risk to fish populations exposed to this major coal ash release.« less

  8. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect (OSTI)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  9. Protein Instability and Lou Gehrig's Disease

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

    1941 at the age of only 38. Recently, an award-winning movie about the famous physicist, Stephen Hawking, depicted the disease's devastating physical toll. ALS kills by destroying...

  10. Visualizing Brain Metals in Health and Disease

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

    Visualizing Brain Metals in Health and Disease figure 1 Fig. 1. Rapid-scanning x-ray ... The beam intensity was monitored with a N2-filled ion chamber (I0). The brain slice was ...

  11. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect (OSTI)

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  12. Global disease monitoring and forecasting with Wikipedia

    SciTech Connect (OSTI)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.

  13. Chronic beryllium disease: Diagnosis and management

    SciTech Connect (OSTI)

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  14. Global disease monitoring and forecasting with Wikipedia

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

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: accessmore » logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.« less

  15. Treatment of Anthrax Disease Frequently Asked Questions

    SciTech Connect (OSTI)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  16. Science On Tap - Understanding HIV and Infectious Diseases

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

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine...

  17. Software speeds detection of diseases and cancer-treatment targets

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

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of...

  18. Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease

    Broader source: Energy.gov [DOE]

    This document provides a listing of medical facilities within the United States with experience in evaluating Chronic Beryllium Disease.

  19. NIOSH Alert-Preventing Sentization and Disease from Beryllium | Department

    Office of Environmental Management (EM)

    of Energy NIOSH Alert-Preventing Sentization and Disease from Beryllium NIOSH Alert-Preventing Sentization and Disease from Beryllium February 3, 2011 Preventing Sensitization and Disease from Beryllium Exposure The National Institute for Occupational Safety and Health (NIOSH) requests assistance in preventing beryllium sensitization and chronic beryllium disease. Development of these conditions requires exposure to beryllium and is affected by both job tasks and genetic factors. Some jobs

  20. Automated diagnostic kiosk for diagnosing diseases

    DOE Patents [OSTI]

    Regan, John Frederick; Birch, James Michael

    2014-02-11

    An automated and autonomous diagnostic apparatus that is capable of dispensing collection vials and collections kits to users interesting in collecting a biological sample and submitting their collected sample contained within a collection vial into the apparatus for automated diagnostic services. The user communicates with the apparatus through a touch-screen monitor. A user is able to enter personnel information into the apparatus including medical history, insurance information, co-payment, and answer a series of questions regarding their illness, which is used to determine the assay most likely to yield a positive result. Remotely-located physicians can communicate with users of the apparatus using video tele-medicine and request specific assays to be performed. The apparatus archives submitted samples for additional testing. Users may receive their assay results electronically. Users may allow the uploading of their diagnoses into a central databank for disease surveillance purposes.

  1. Optical detection dental disease using polarized light

    DOE Patents [OSTI]

    Everett, Matthew J. (Livermore, CA); Colston, Jr., Billy W. (Livermore, CA); Sathyam, Ujwal S. (Livermore, CA); Da Silva, Luiz B. (Danville, CA); Fried, Daniel (San Francisco, CA)

    2003-01-01

    A polarization sensitive optical imaging system is used to detect changes in polarization in dental tissues to aid the diagnosis of dental disease such as caries. The degree of depolarization is measured by illuminating the dental tissue with polarized light and measuring the polarization state of the backscattered light. The polarization state of this reflected light is analyzed using optical polarimetric imaging techniques. A hand-held fiber optic dental probe is used in vivo to direct the incident beam to the dental tissue and collect the reflected light. To provide depth-resolved characterization of the dental tissue, the polarization diagnostics may be incorporated into optical coherence domain reflectometry and optical coherence tomography (OCDR/OCT) systems, which enables identification of subsurface depolarization sites associated with demineralization of enamel or bone.

  2. Chronic Beryllium Disease Prevention Program Report

    SciTech Connect (OSTI)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  3. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's penumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  4. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's pneumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  5. Inexpensive handheld tests for diseases are in sight

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

    Inexpensive handheld tests for diseases are in sight Inexpensive handheld tests for diseases are in sight Los Alamos scientists are developing a prototype of handheld tests capable of diagnose multiple diseases. April 3, 2012 The technical founders of Mesa Tech International are working to execute the first proof of principle of the "DNThe technical founders of Mesa Tech International are working to execute the first proof of principle of the DNA Dipstick technology that has been licensed

  6. Counting small RNA in disease-causing organisms

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

    Counting small RNA in disease-causing organisms Counting small RNA in disease-causing organisms Los Alamos researchers demonstrated improved technical methods capable of directly counting small RNA molecules in pathogenic (disease-causing) bacteria. June 17, 2013 Artist's concept of the fluorescence labeling and detection of small RNA in pathogenic bacteria. Artist's concept of the fluorescence labeling and detection of small RNA in pathogenic bacteria. The new technique reduced the number of

  7. Counting small RNA in disease-causing organisms

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

    Counting small RNA in disease-causing organisms Counting small RNA in disease-causing organisms Los Alamos researchers demonstrated improved technical methods capable of directly counting small RNA molecules in pathogenic (disease-causing) bacteria. June 17, 2013 Artist's concept of the fluorescence labeling and detection of small RNA in pathogenic bacteria. Artist's concept of the fluorescence labeling and detection of small RNA in pathogenic bacteria. The new technique reduced the number of

  8. Analyzing genetic tree sheds new light on disease outbreaks

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

    News Releases » News Releases - 2016 » February » Analyzing genetic tree sheds new light on disease outbreaks Analyzing genetic tree sheds new light on disease outbreaks The team used computational phylogenetic analysis to examine how strains of HIV, both in computer modeling and compared with real-life case studies, would be transmitted. February 25, 2016 Using computational techniques, scientists at Los Alamos National Laboratory are working to more clearly understand how diseases such as

  9. Proteins' Amazing Origami Powers: Insight for Potential Disease Treatments

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

    | Department of Energy Proteins' Amazing Origami Powers: Insight for Potential Disease Treatments Proteins' Amazing Origami Powers: Insight for Potential Disease Treatments October 4, 2011 - 12:46pm Addthis This is a visualization of drug molecules ("parade day-like balloons") in a simulated attack of the ribbon-like protein fibrils that are believed to be the cause of Alzheimer’s disease. <a

  10. Chronic Beryllium Disease Prevention Program (10 CFR 850) | Department of

    Office of Environmental Management (EM)

    Energy Chronic Beryllium Disease Prevention Program (10 CFR 850) Chronic Beryllium Disease Prevention Program (10 CFR 850) The DOE established a chronic beryllium disease prevention program (CBDPP) to reduce the number of workers currently exposed to beryllium in the course of their work at DOE facilities managed by DOE or its contractors, minimize the levels of, and potential for, exposure to beryllium, and establish medical surveillance requirements to ensure early detection of the

  11. Methods of treating parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys (Garrett Park, MD); Cunningham, Janet (Alameda, CA)

    2009-05-19

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the CNS are provided. Also provided are methods of treating Parkinson's Disease.

  12. Indoor air quality & airborne disease control in healthcare facilities...

    Office of Scientific and Technical Information (OSTI)

    Subject: 32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION; MEDICAL ESTABLISHMENTS; INDOOR AIR POLLUTION; CONTROL SYSTEMS; DISEASES; THERMAL COMFORT; SPACE HVAC SYSTEMS Word ...

  13. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOE Patents [OSTI]

    Whitley, Richard J.; Roizman, Bernard

    2010-06-29

    Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

  14. Structure of the Newcastle disease virus hemagglutinin-neuraminidase...

    Office of Scientific and Technical Information (OSTI)

    virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus ...

  15. AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS...

    Office of Scientific and Technical Information (OSTI)

    Converting energy to medical progress nuclear medicine NONE 62 RADIOLOGY AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS; NUCLEAR MEDICINE; PATIENTS; RADIATION...

  16. Update on the Hanford Site Chronic Beryllium Disease Prevention...

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

    Chronic Beryllium Disease Prevention Program (CBDPP) Stan Branch Richland Operations Office Hanford Advisory Board Health, Safety and Environmental Protection Committee January 7,...

  17. Software speeds detection of diseases and cancer-treatment targets

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

    Software speeds detection of diseases and cancer-treatment targets Alumni Link: Opportunities, News and Resources for Former Employees Latest Issue:September 2015 all issues All...

  18. Asbestos-related pulmonary disease in boilermakers

    SciTech Connect (OSTI)

    Demers, R.Y.; Neale, A.V.; Robins, T.; Herman, S.C. )

    1990-01-01

    Boilermakers are skilled building tradesmen who construct, repair, and dismantle boilers. The present study reports on the evaluation of members of a Michigan boilermaker's union for the presence of signs and symptoms of chronic pulmonary disease. Study variables included standardized evaluations of chest x-ray findings, pulmonary function testing, physical examination, and respiratory symptoms. An overall participation rate of 69% was achieved. A non-participant survey identified no significant differences between participants and non-participants in dyspnea, cough, age, or smoking history. Among participants with greater than 20 years experience in the trade, the mean FVC was 91% of predicted; the FEV1 was 86% of predicted; 25% showed at least a 1/0 profusion of interstitial markings on chest x-ray; 30% had bilateral pleural abnormalities; and 52% had audible inspiratory rales on physical examination. Forced vital capacity and forced expiratory volume at one second both decreased with years in the trade. Chest x-ray findings of interstitial fibrosis and pleural plaques were related to ten or more years in the trade, as were respiratory symptoms of pulmonary rales, wheeze, and dyspnea.

  19. Array-based detection of genetic alterations associated with disease

    DOE Patents [OSTI]

    Pinkel, Daniel; Albertson, Donna G.; Gray, Joe W.

    2007-09-11

    The present invention relates to DNA sequences from regions of copy number change on chromosome 20. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases.

  20. Update on the Hanford Site Chronic Beryllium Disease Prevention...

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

    by DOE- EM on March 13, 2013 2 Be CAP Status * Rev. 1 of the Hanford site wide Chronic Beryllium Disease Prevention Program (CBDPP) was approved by DOE March 7, 2012 * Rev....

  1. Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases...

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

    These studies have led her from the U.S. Centers for Disease Control and Prevention to Lyon, France, where she was instrumental in designing, constructing and making operational a...

  2. Timing of testing and treatment for asymptomatic diseases

    SciTech Connect (OSTI)

    K?rk?zlar, Eser; Faissol, Daniel M.; Griffin, Paul M.; Swann, Julie L.

    2010-07-01

    Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases. We provide a computationally efficient method for determining a cost-effective dynamic intervention strategy that takes into account (i) the results of the previous test for each individual and (ii) the change in the individual’s behavior based on awareness of the disease. We demonstrate the usefulness of the approach by applying the results to screening decisions for Hepatitis C (HCV) using medical data, and compare our findings to current HCV screening recommendations.

  3. Software speeds detection of diseases and cancer-treatment targets

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

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of identifying DNA from viruses and all parts of the Tree of Life. December 1, 2014 With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. Contact

  4. Science On Tap - Understanding HIV and Infectious Diseases

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

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine Room 145 Central Park Square, Los Alamos, New Mexico, 87544 USA SPEAKER: Ruy Ribeiro, Los Alamos National Laboratory CONTACT: Jessica Privette 505 667-0375 CATEGORY: Bradbury INTERNAL: Calendar Login Science On Tap - Every Third Thursday Event Description Science On Tap happens every third Thursday of the month, featuring

  5. Indoor air quality & airborne disease control in healthcare facilities

    Office of Scientific and Technical Information (OSTI)

    (Conference) | SciTech Connect Conference: Indoor air quality & airborne disease control in healthcare facilities Citation Details In-Document Search Title: Indoor air quality & airborne disease control in healthcare facilities This article is concerned with indoor air quality (IAQ) in the context of healthcare facilities. It defines what is meant by IAQ, lists health outcomes of poor IAQ, addresses specific healthcare IAQ issues, discusses solutions by means of HVAC systems, and

  6. Engineering disease resistance with pectate lyase-like genes

    DOE Patents [OSTI]

    Vogel, John; Somerville, Shauna

    2005-03-08

    A mutant gene coding for pectate lyase and homologs thereof is provided, which when incorporated in transgenic plants effect an increased level disease resistance in such plants. Also is provided the polypeptide sequence for the pectate lyase of the present invention. Methods of obtaining the mutant gene, producing transgenic plants which include the nucleotide sequence for the mutant gene and producing improved disease resistance in a crop of such transgenic plants are also provided.

  7. Platform for Pre-Symptomatic Detection of Citrus Disease

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

    Citrus Disease Detection Platform Platform for Pre-Symptomatic Detection of Citrus Disease LANS is currently seeking an industry partner(s) to assist with the commercial deployment of the detection platform described below. Submit your Commercialization Proposal to lanldx@lanl.gov before 11:59 PM on Thursday, March 10, 2016. Submit your Proposal thumbnail of Kathleen McDonald Head of Intellectual Property, Business Development Executive Kathleen McDonald Richard P. Feynman Center for Innovation

  8. LANL spinoff receives NIH grant for respiratory disease diagnostic device

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

    LANL spinoff receives NIH grant LANL spinoff receives NIH grant for respiratory disease diagnostic device Mesa Tech has been awarded a grant to develop an inexpensive, instrument-free, nucleic-acid testing device to diagnose various respiratory diseases in record time. October 19, 2011 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

  9. Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN)

    Office of Scientific and Technical Information (OSTI)

    ectodomain reveals a four-helix bundle stalk (Journal Article) | SciTech Connect of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid

  10. Metabolic Prosthesis for Treating Ischemic Diseases - Energy Innovation

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

    Portal Advanced Materials Advanced Materials Find More Like This Return to Search Metabolic Prosthesis for Treating Ischemic Diseases Oak Ridge National Laboratory Contact ORNL About This Technology Publications: PDF Document Publication ID 200501658.pdf (555 KB) Technology Marketing SummaryORNL researchers have developed a new approach for treating ischemic diseases that will deliver oxygen directly to affected tissues by electrolysis of body fluids. Numerous treatments currently exist or

  11. Bush Administration to Expand Beryllium Disease Screening Program |

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

    Department of Energy Bush Administration to Expand Beryllium Disease Screening Program Bush Administration to Expand Beryllium Disease Screening Program February 23, 2005 - 10:27am Addthis Former employees of DOE vendors eligible for free screening WASHINGTON, DC - U.S. Secretary of Energy Samuel W. Bodman today announced the Department of Energy (DOE) will expand a beryllium screening program to include former employees of now-defunct DOE beryllium vendor companies across the country.

  12. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect (OSTI)

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  13. Airborne spread of foot-and-mouth disease - model intercomparison

    SciTech Connect (OSTI)

    Gloster, J; Jones, A; Redington, A; Burgin, L; Sorensen, J H; Turner, R; Dillon, M; Hullinger, P; Simpson, M; Astrup, P; Garner, G; Stewart, P; D'Amours, R; Sellers, R; Paton, D

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office during 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.

  14. Investigation of saliva of patients with periodontal disease using NAA

    SciTech Connect (OSTI)

    Zamboni, C. B.; Metairon, S.; Medeiros, I. M. M. A.

    2013-05-06

    In this study the non-stimulated whole saliva of 26 healthy subjects (mean age 33.9 {+-} 11.0 years, range: 26 to 49 years) and 11 patients with periodontal disease (mean age 41.7 {+-} 11.5 years; range 29 to 55 years) was investigated using Neutron Activation Analysis (NAA) technique. The samples were obtained from donors at Sao Paulo city (Brazil). The analyses were performed in the nuclear reactor IEA-R1 (3.5-4.5MW, pool type) at IPEN/CNEN-SP (Brazil). Considerable changes in Ca and S saliva's level were identified in patients with periodontal disease suggesting they can be used as monitors of periodontal diseases.

  15. Remote sensing, global warming, and vector-borne disease

    SciTech Connect (OSTI)

    Wood, B.; Beck, L.; Dister, S.; Lobitz, B.

    1997-12-31

    The relationship between climate change and the pattern of vector-borne disease can be viewed at a variety of spatial and temporal scales. At one extreme are changes such as global warming, which are continental in scale and occur over periods of years, decades, or longer. At the opposite extreme are changes associated with severe weather events, which can occur at local and regional scales over periods of days, weeks, or months. Key ecological factors affecting the distribution of vector-borne diseases include temperature, precipitation, and habitat availability, and their impact on vectors, pathogens, reservoirs, and hosts. Global warming can potentially alter these factors, thereby affecting the spatial and temporal patterns of disease.

  16. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

    Xia, Jing; Rocke, David M.; Perry, George; Ray, Monika

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  17. Compositions and Methods for the Treatment of Pierce's Disease

    DOE Patents [OSTI]

    Gupta, Goutam (Santa Fe, NM)

    2008-10-07

    Chimeric anti-microbial proteins, compositions, and methods for the therapeutic and prophylactic treatment of plant diseases caused by the bacterial pathogen Xylella fastidiosa are provided. The anti-microbial proteins of the invention generally comprise a surface recognition domain polypeptide, capable of binding to a bacterial membrane component, fused to a bacterial lysis domain polypeptide, capable of affecting lysis or rupture of the bacterial membrane, typically via a fused polypeptide linker. In particular, methods and compositions for the treatment or prevention of Pierce's disease of grapevines are provided. Methods for the generation of transgenic Vitus vinefera plants expressing xylem-secreted anti-microbial chimeras are also provided.

  18. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Office of Environmental Management (EM)

    federal register Wednesday December 8, 1999 Part III Department of Energy 10 CFR Part 850 Chronic Beryllium Disease Prevention Program; Final Rule VerDate 29-OCT-99 10:58 Dec 07, 1999 Jkt 190000 PO 00000 Frm 00001 Fmt 4717 Sfmt 4717 E:\FR\FM\A08DE0.189 pfrm04 PsN: 08DER3 68854 Federal Register / Vol. 64, No. 235 / Wednesday, December 8, 1999 / Rules and Regulations DEPARTMENT OF ENERGY 10 CFR Part 850 [Docket No. EH-RM-98-BRYLM] RIN 1901-AA75 Chronic Beryllium Disease Prevention Program AGENCY:

  19. Azasugar inhibitors as pharmacological chaperones for Krabbe disease

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

    Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

    2015-03-23

    Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe amore » new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.« less

  20. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    SciTech Connect (OSTI)

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; Vasant, Drashtti; Brookes, Anthony J.; Zankl, Andreas; Washington, Nicole L.; Mungall, Christopher J.; Lewis, Suzanna E.; Haendel, Melissa A.; Parkinson, Helen; Robinson, Peter N.

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.

  1. Using Genomics to Study Human Biology and Disease

    SciTech Connect (OSTI)

    Myers, Ricard M.

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  2. Platform for Pre-Symptomatic Detection of Citrus Disease

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

    Platform for Pre-Symptomatic Detection of Citrus Disease February 18, 2016 Request for Proposal Los Alamos National Security, LLC (LANS) is the manager and operator of Los Alamos National Laboratory (Los Alamos) for the U.S. Department of Energy National Nuclear Security Administration under contract DE-AC52-06NA25396. Los Alamos is a mission- centric Federally Funded Research and Development Center focused on solving critical national security challenges through science and engineering for both

  3. Radiological approaches in the evaluation of joint disease in children

    SciTech Connect (OSTI)

    Poznanski, A.K.; Conway, J.J.; Shkolnik, A.; Pachman, L.M.

    1987-04-01

    In summary, the newer technologies in radiology have allowed us to visualize more clearly the manifestation of joint disease in children. The presence of small erosions and cartilage damage can be seen much better with magnetic resonance imaging than with any other modality short of arthrography, a much more invasive examination. Joint effusion, although sometimes visualized with conventional radiography, is probably best recognized with ultrasound or magnetic resonance imaging, although it can be detected with computed tomography as well. For the evaluation of avascular necrosis that can be associated with steroid use in joint disease, bone scintigraphy is a simple, sensitive method. Magnetic resonance may be as or more sensitive and gives additional information as well. In the detection of change with time, conventional radiography probably will remain the standard as it is still the simplest, least expensive examination; however, it has many limitations in specific cases. Bone scintigraphy may be of value in selected cases. Although we have still not had enough experience with magnetic resonance imaging to use it as a way of evaluating progress of joint disease, it promises to be the most sensitive radiologic measure of evaluating progress as small anatomical changes can be detected within the cartilage, which cannot be done easily with other means. 27 references.

  4. Statistical Mechanics of Prion Diseases (Journal Article) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Statistical Mechanics of Prion Diseases Citation Details In-Document Search Title: Statistical Mechanics of Prion Diseases We present a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., mad cow disease) with concomitant prion protein misfolding and aggregation. Our studies lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale

  5. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect (OSTI)

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  6. Development of Biomarkers for Chronic Beryllium Disease in Mice

    SciTech Connect (OSTI)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and Â?normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify changes in potential protein biomarkers in beryllium-treated mice. We will correlate these findings with the ability of the transgenic mice to develop a beryllium-specific adaptive immune response in blood and bronchoalveolar lavage (BAL) fluid. We will also determine whether beryllium-responsive CD4+ T cells in blood and BAL correlate with the onset of granuloma formation. Thus, we will provide the scientific community with biomarkers of sensitization and disease progression for CBD. These biomarkers will serve as critical tools for development of improved industrial hygiene and therapeutic interventions.

  7. Osteogenic Sarcoma of the Maxilla: Neutron Therapy for Unresectable Disease

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

    Smoron, Geoffrey L.; Lennox, Arlene J.; Mcgee, James L.

    1999-01-01

    Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla. Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor. Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days. Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontalmore » sinus, orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up. Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.« less

  8. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    SciTech Connect (OSTI)

    Wadhwa, Ashutosh [University of Tennessee, Center for Wildlife Health, Department of Forestry; Foote, Robert [ORNL; Shaw, Robert W [ORNL; Eda, Shigetoshi [ORNL

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types of SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was observed. In a further experiment, we magnetically immobilized antigen-coated beads in a microchannel, reacted the beads with serum and SAB in the channel, and detected antibody binding to the beads in the microfluidic system. A strong antibody binding in JD-positive serum was detected, whereas there was only negligible binding in negative control experiments. Our data suggest that the bead-based microfluidic system may form a basis for development of an on-site serodiagnosis of JD. Key Words: Mycobacterium avium ssp. paratuberculosis, Johne s disease, microfluidics, lab-on-a-chip.

  9. Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease

    SciTech Connect (OSTI)

    Balestra, D.J.; Balestra, S.T.; Wasson, J.H.

    1988-07-01

    The authors describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitital and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

  10. Resource Requirements Planning for Hospitals Treating Serious Infectious Disease Cases.

    SciTech Connect (OSTI)

    Vugrin, Eric D.; Verzi, Stephen Joseph; Finley, Patrick D.; Turnquist, Mark A.; Wyte-Lake, Tamar; Griffin, Ann R.; Ricci, Karen J.; Plotinsky, Rachel

    2015-02-01

    This report presents a mathematical model of the way in which a hospital uses a variety of resources, utilities and consumables to provide care to a set of in-patients, and how that hospital might adapt to provide treatment to a few patients with a serious infectious disease, like the Ebola virus. The intended purpose of the model is to support requirements planning studies, so that hospitals may be better prepared for situations that are likely to strain their available resources. The current model is a prototype designed to present the basic structural elements of a requirements planning analysis. Some simple illustrati ve experiments establish the mo del's general capabilities. With additional inve stment in model enhancement a nd calibration, this prototype could be developed into a useful planning tool for ho spital administrators and health care policy makers.

  11. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

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

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; et al

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000more »rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.« less

  12. "A State-Wide Research Network for Alzheimer'sDisease"

    Office of Scientific and Technical Information (OSTI)

    ... of Alzheimer's disease in a rural Southern African American cohort. ... South Carolina: Opportunities for public health intervention. Journal of the South Carolina Medical ...

  13. Toxicological and pharmacological concerns on oxidative stress and related diseases

    SciTech Connect (OSTI)

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    2013-12-15

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

  14. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    SciTech Connect (OSTI)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  15. Proceedings of the 2nd workshop on lyme disease in the Southeast

    SciTech Connect (OSTI)

    Apperson, C.S.; Levine, J.F.; Snoddy, E.L.

    1993-12-31

    This volume provides author prepared abstracts of oral presentation at the Second Workshop on Lyme Disease in the Southeast head in Raleigh, North Carolina September 7-9, 1993. The 33 presentations covered various aspects of the epidemic including geographical distribution of various species of ticks, transmission risks, Lyme Disease epidemiology, and taxonomic aspects.

  16. Multi-analyte analysis of saliva biomarkers as predictors of periodontal and pre-implant disease

    DOE Patents [OSTI]

    Braun, Thomas; Giannobile, William V; Herr, Amy E; Singh, Anup K; Shelburne, Charlie

    2015-04-07

    The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal and/or peri-implant disease. More specifically, the invention provides a panel of biomarkers that, when used in combination, can allow determination of the probability of a periodontal and/or peri-implant disease state with extremely high accuracy.

  17. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study

    SciTech Connect (OSTI)

    Schimmel, J.G. . Social and Economic Sciences Research Center); Beck, D.M. )

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  18. Mineral density volume gradients in normal and diseased human tissues

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

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-raymore » fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.« less

  19. Mineral density volume gradients in normal and diseased human tissues

    SciTech Connect (OSTI)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  20. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    SciTech Connect (OSTI)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; Remais, Justin V.

    2014-12-01

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delay China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.

  1. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    ScienceCinema (OSTI)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2014-05-06

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  2. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    SciTech Connect (OSTI)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  3. Using Social Media for Actionable Disease Surveillance and Outbreak Management: A Systematic Literature Review

    SciTech Connect (OSTI)

    Charles-Smith, Lauren E.; Reynolds, Tera; Cameron, Mark; Conway, Mike; Lau, Eric H.; Olsen, Jennifer; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura; Suda, Katie; Corley, Courtney D.

    2015-10-05

    Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.

  4. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect (OSTI)

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  5. Integrating Heterogeneous Healthcare Datasets and Visual Analytics for Disease Bio-surveillance and Dynamics

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Steed, Chad A; Quinn, Shannon; Chennubhotla, Chakra; Parker, Tara L

    2013-01-01

    n this paper, we present an overview of the big data chal- lenges in disease bio-surveillance and then discuss the use of visual analytics for integrating data and turning it into knowl- edge. We will explore two integration scenarios: (1) combining text and multimedia sources to improve situational awareness and (2) enhancing disease spread model data with real-time bio-surveillance data. Together, the proposed integration methodologies can improve awareness about when, where and how emerging diseases can affect wide geographic regions.

  6. Global warming and the potential spread of vector-borne diseases

    SciTech Connect (OSTI)

    Patz, J.

    1996-12-31

    Climatic factors influence many vector-borne infectious diseases, in addition to demographic, biological, and ecological determinants. The United Nation`s Intergovernmental Panel on Climate Change (IPCC) estimates an unprecedented global rise of 2.0 C by the year 2100. Of major concern is that these changes can affect the spread of many serious infectious diseases, including malaria and dengue fever. Global warming would directly affect disease transmission by shifting the mosquito`s geographic range, increasing reproductive and biting rates, and shortening pathogen incubation period. Human migration and damage to health infrastructures from the projected increase in climate variability and sea level rise could indirectly contribute to disease transmission. A review of this literature, as well as preliminary data from ongoing studies will be presented.

  7. Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program

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

    Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program June 2010 Office of Independent Oversight Office of Health, Safety and Security Office of Health, Safety and Security HSS x Hanford Site Chronic Beryllium Disease Prevention Program | i Abbreviations iii Executive Summary v 1 Introduction 1 2 Management and Oversight 3 3 Findings Requiring Corrective Action 14 4 Conclusions and Cross-Cutting Opportunities for Improvement 17 Appendix A - Supplemental

  8. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    SciTech Connect (OSTI)

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  9. Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

    SciTech Connect (OSTI)

    Vi, Linda; Feng, Lucy; Zhu, Rebecca D.; Wu, Yan; Lawson Health Research Institute, London, Ontario ; Satish, Latha; Gan, Bing Siang; Lawson Health Research Institute, London, Ontario; Department of Surgery, University of Western Ontario, London, Ontario; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario; Department of Medical Biophysics, University of Western Ontario, London, Ontario ; O'Gorman, David B.

    2009-12-10

    Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, {alpha} smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

  10. Percutaneous Cholangioscopy in the Management of Biliary Disease: Experience in 25 Patients

    SciTech Connect (OSTI)

    Hatzidakis, Adam A.; Alexandrakis, George; Kouroumalis, Helias; Gourtsoyiannis, Nicholas C.

    2000-11-15

    Purpose: To present our experience performing percutaneous cholangioscopy in the management of 25 patients with biliary disease.Methods: During the last 3 years, 26 percutaneous cholangioscopies were performed in 25 patients with common bile duct disease (n = 16), intrahepatic ducts disease (n = 6), and gallbladder disease (n = 4). Our patient population group included seven with common bile duct stones, three with intrahepatic lithiasis, and eight with benign strictures (six iatrogenic and two postinflammatory). In four patients malignancy was to be excluded, in two the tumor extent was to be evaluated, whereas in one case the correct placement of a metallic stent needed to be controlled. A 9.9 Fr flexible endoscope URF-P (Olympus, 1.2 mm working channel, 70-cm length) was used.Results: In total, percutaneous cholangioscopy answered 30 diagnostic questions, was technically helpful in 19 cases (performing lithotripsy or biopsy or guiding a wire), and of therapeutic help in 12 (performing stone retrieval). In 24 of 26 cases the therapeutic decision and the patient management changed because of the findings or because of the help of the method. In two cases biliary intervention failed to treat the cause of the disease. No major complication due to the use of the endoscopy was noted.Conclusions: Percutaneous cholangioscopy is a very useful tool in the management of patients with biliary disease. The method can help in diagnosis, in performing complex interventional procedures, and in making or changing therapeutic decisions.

  11. Multiplexed Molecular Assays for Rapid Rule-Out of Foot-and-Mouth Disease

    SciTech Connect (OSTI)

    Lenhoff, R; Naraghi-Arani, P; Thissen, J; Olivas, J; Carillo, C; Chinn, C; Rasmussen, M; Messenger, S; Suer, L; Smith, S M; Tammero, L; Vitalis, E; Slezak, T R; Hullinger, P J; Hindson, B J; Hietala, S; Crossley, B; Mcbride, M

    2007-06-26

    A nucleic acid-based multiplexed assay was developed that combines detection of foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign animal diseases and four domestic animal diseases that cause vesicular or ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and swine. The FMDV 'look-alike' diagnostic assay panel contains five PCR and twelve reverse transcriptase PCR (RT-PCR) signatures for a total of seventeen simultaneous PCR amplifications for seven diseases plus incorporating four internal assay controls. It was developed and optimized to amplify both DNA and RNA viruses simultaneously in a single tube and employs Luminex{trademark} liquid array technology. Assay development including selection of appropriate controls, a comparison of signature performance in single and multiplex testing against target nucleic acids, as well of limits of detection for each of the individual signatures is presented. While this assay is a prototype and by no means a comprehensive test for FMDV 'look-alike' viruses, an assay of this type is envisioned to have benefit to a laboratory network in routine surveillance and possibly for post-outbreak proof of freedom from foot-and-mouth disease.

  12. Severe gas bubble disease in a warmwater fishery in the midwestern united states

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Supersaturation of the water of the Osage River below the Harry S. Truman Dam resulted in an epidemic of gas bubble disease that caused the largest fish kill in the history of Missouri. This is the first recorded evidence of serious supersaturation in the midwestern U.S. Total gas saturation levels up to 139% killed nearly 500,000 fish in the Osage River and the Lake of the Ozarks during April-May 1978. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in pelagic and near-shore species, deepwater species, and bottom-dwelling species. Susceptibility to disease was related to fish size.

  13. Severe gas bubble disease in a warmwater fishery in the midwestern United States

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Gas bubble disease below Harry S. Truman Dam, sited on the upper Osage River and spilling into Lake of the Ozarks, caused the largest fish kill on record in Missouri. This is the first recorded evidence of serious supersaturation in the Midwest. Total gas saturation levels up to 139% killed nearly a half million fish in the upper 85 km of the Osage Arm, Lake of the Ozarks, during April to June, 1978 and 1979. Gas supersaturation occurred throughout the 150 km of this main-stem reservoir. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Pelagic and near-shore species suffered the earliest and heaviest mortalities, but fish characteristic of deeper waters were increasingly killed as supersaturation persisted. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in bottom-dwelling fish of several species, due to long-term intermittent exposure. Susceptibility to gas bubble disease was related to fish size.

  14. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    SciTech Connect (OSTI)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-02-01

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

  15. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    SciTech Connect (OSTI)

    Kaper, Tasso J. Kramer, Mark A.; Rotstein, Horacio G.

    2013-12-15

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

  16. Serum Proteome Profiles in Stricturing Crohn’s Disease: A pilot study.

    SciTech Connect (OSTI)

    Townsend, Peter; Zhang, Qibin; Shapiro, Jason; Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Schepmoes, Athena A.; Weitz, Karl K.; Mallette, Meaghan; Moniz, Heather; Bright, Renee; Merrick, Marjorie; Shah, Samir A.; Sands, Bruce E.; Leleiko, Neal

    2015-08-01

    Background: Crohn’s disease (CD) is a form of inflammatory bowel disease (IBD) with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of IBD. We performed a pilot study to examine differences in the proteome among patients with stricturing Crohn’s disease, non-stricturing Crohn’s disease, and ulcerative colitis (UC). Methods: Serum samples were selected from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), an established cohort of patients with IBD. Crohn’s disease patients with surgically-resected stricture were matched with similar patients with Crohn’s disease without known stricture, and with UC. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture. Results: Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the three groups. We quantified 7668 peptides and 897 proteins for analysis. ROC analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides, and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides, and determined their function based on previously published literature. Conclusions: The serum of patients with stricturing CD, non-stricturing CD, and UC are distinguishable via proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.

  17. Gas Bubble Disease Monitoring and Research of Juvenile Salmonids : Annual Report 1996.

    SciTech Connect (OSTI)

    Maule, Alec G.; Beeman, John W.; Hans, Karen M.; Mesa, M.G.; Haner, P.; Warren, J.J.

    1997-10-01

    This document describes the project activities 1996--1997 contract year. This report is composed of three chapters which contain data and analyses of the three main elements of the project: field research to determine the vertical distribution of migrating juvenile salmonids, monitoring of juvenile migrants at dams on the Snake and Columbia rivers, and laboratory experiments to describe the progression of gas bubble disease signs leading to mortality. The major findings described in this report are: A miniature pressure-sensitive radio transmitter was found to be accurate and precise and, after compensation for water temperature, can be used to determine the depth of tagged-fish to within 0.32 m of the true depth (Chapter 1). Preliminary data from very few fish suggest that depth protects migrating juvenile steelhead from total dissolved gas supersaturation (Chapter 1). As in 1995, few fish had any signs of gas bubble disease, but it appeared that prevalence and severity increased as fish migrated downstream and in response to changing gas supersaturation (Chapter 2). It appeared to gas bubble disease was not a threat to migrating juvenile salmonids when total dissolved gas supersaturation was < 120% (Chapter 2). Laboratory studies suggest that external examinations are appropriate for determining the severity of gas bubble disease in juvenile salmonids (Chapter 3). The authors developed a new method for examining gill arches for intravascular bubbles by clamping the ventral aorta to reduce bleeding when arches were removed (Chapter 3). Despite an outbreak of bacterial kidney disease in the experimental fish, the data indicate that gas bubble disease is a progressive trauma that can be monitored (Chapter 3).

  18. Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases |

    Office of Environmental Management (EM)

    Department of Energy 4.01.2011]: A Discovery to Fight Cancer and Other Diseases Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases April 1, 2011 - 5:52pm Addthis Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible hinge in Rad50 near the Mre11 binding site | Courtesy of Lawrence Berkeley National Laboratory Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible

  19. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

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

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; et al

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motormore » decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.« less

  20. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    SciTech Connect (OSTI)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; McKinnon, Peter

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.

  1. General Counsel Legal Interpretation Regarding Medical Removal Protection Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Broader source: Energy.gov [DOE]

    The following document is the Office of the General Counsel (GC) interpretation regarding Medical Removal Protection Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program.

  2. Higher coronary heart disease and heart attack morbidity in Appalachian coal mining regions

    SciTech Connect (OSTI)

    Hendryx, M.; Zullig, K.J.

    2009-11-15

    This study analyzes the U.S. 2006 Behavioral Risk Factor Surveillance System survey data (N = 235,783) to test whether self-reported cardiovascular disease rates are higher in Appalachian coal mining counties compared to other counties after control for other risks. Dependent variables include self-reported measures of ever (1) being diagnosed with cardiovascular disease (CVD) or with a specific form of CVD including (2) stroke, (3) heart attack, or (4) angina or coronary heart disease (CHD). Independent variables included coal mining, smoking, BMI, drinking, physician supply, diabetes co-morbidity, age, race/ethnicity, education, income, and others. SUDAAN Multilog models were estimated, and odds ratios tested for coal mining effects. After control for covariates, people in Appalachian coal mining areas reported significantly higher risk of CVD (OR = 1.22, 95% CI = 1.14-1.30), angina or CHO (OR = 1.29, 95% C1 = 1.19-1.39) and heart attack (OR = 1.19, 95% C1 = 1.10-1.30). Effects were present for both men and women. Cardiovascular diseases have been linked to both air and water contamination in ways consistent with toxicants found in coal and coal processing. Future research is indicated to assess air and water quality in coal mining communities in Appalachia, with corresponding environmental programs and standards established as indicated.

  3. Implementation Guide for use with 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

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

    2001-01-04

    The Department of Energy (DOE) has established regulatory requirements for the Chronic Beryllium Disease Prevention Program (CBDPP) in Title 10 of the Code of Federal Regulations (CFR), Part 850 (10 CFR 850) [64 Federal Register (FR) 68854]. Supersedes DOE G 440.1-7. Certified 9-23-10.

  4. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study. Hanford Environmental Dose Reconstruction Project

    SciTech Connect (OSTI)

    Schimmel, J.G.; Beck, D.M.

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  5. Portable microfluidic raman system for rapid, label-free early disease signature detection

    SciTech Connect (OSTI)

    Wu, Meiye; Davis, Ryan Wesley; Hatch, Anson

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  6. Determining the risk of cardiovascular disease using ion mobility of lipoproteins

    DOE Patents [OSTI]

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-05-11

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  7. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    SciTech Connect (OSTI)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  8. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ? Altered hepatic bile acid composition is observed in progressive NAFLD. ? Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ? Increased levels of taurine and conjugated bile acids are observed in NASH. ? Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.

  9. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect (OSTI)

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  10. "Artificial" brains, electrical grids, and disease modeling: Los Alamos

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

    science discoveries unveiled September 15 Science discoveries unveiled "Artificial" brains, electrical grids, and disease modeling: Los Alamos science discoveries unveiled September 15 The event is an opportunity for business leaders and community members to learn about where science is heading, as well as for students to discover potential new career directions. September 8, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez

  11. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect (OSTI)

    Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032 ; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin; Institutes of Biomedical Science, Fudan University, Shanghai 200032

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  12. Changes in Gas Bubble Disease Signs for Migrating Juvenile Salmonids Experimentally Exposed to Supersaturated Gasses, 1996-1997 Progress Report.

    SciTech Connect (OSTI)

    Absolon, Randall F.

    1999-03-01

    This study was designed to answer the question of whether gas bubble disease (GBD) signs change as a result of the hydrostatic conditions juvenile salmonids encounter when they enter the turbine intake of hydroelectric projects during their downstream migration.

  13. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry Llyn, E-mail: lkestin@beaumont.ed [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wong, Ching-yee Oliver [Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey Harold [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chmielewski, Gary William; Welsh, Robert James [Department of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  14. Cadmium exposure and cardiovascular disease in the 2005 Korea National Health and Nutrition Examination Survey

    SciTech Connect (OSTI)

    Lee, Mi-Sun; Park, Sung Kyun; Hu, Howard; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI ; Lee, Sundong; Department of Preventive Medicine, School of Oriental Medicine, Sangji University, Wonju, Kangwon

    2011-01-15

    Background: Limited epidemiologic data are available concerning the cardiovascular effects of cadmium exposure, although recent studies suggest associations with myocardial infarction and peripheral arterial disease. We examined the associations of cadmium exposure with cardiovascular disease in nationally representative general Korean adults. Methods: We used cross-sectional data on blood cadmium and self-reported diagnoses of ischemic heart disease (IHD), stroke, and hypertension in a sub-sample of 1908 adults, aged 20 years and older, who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). We used survey logistic regression models accounting for the complex sampling design to estimate the odds ratios (OR), adjusting for age, education, income, alcohol, smoking, body mass index, waist circumference, family history of hypertension, blood pressure, and blood lead. Results: The geometric mean of blood cadmium was 1.53 {mu}g/L. After adjusting for potential confounders, an interquartile range (IQR) increase in blood cadmium (0.91 {mu}g/L) was found to be associated with an increased risk for IHD (OR 2.1, 95% confidence interval (CI) 1.3-3.4). An IQR increase in blood cadmium was found to be associated with an elevated risk for hypertension only among men (OR 1.4, 95% CI 1.1-1.8) but not among women. No association was observed with stroke in both genders. Conclusions: These findings suggest that cadmium in blood may be associated with an increased risk for IHD and hypertension in the general Korean adult population.

  15. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Quinn, Shannon; Chennubhotla, Chakra; Valkova, Silvia

    2014-01-01

    Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

  16. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    Supersaturation of the Columbia and Snake River systems was caused by entrainment of air into water spilling over hydroelectric dams. Total gas saturations of 100% or more have occurred during the spring in each river system. External signs of gas bubble diseases were noted in adult Smallmouth bass and northern squawfish collected from the lower Snake and mid-Columbia rivers during 1975-76. Emboli occurred beneath membranes of the opercula body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several fish.

  17. Root Diseases and Exotic Ecosystems: Implications for Long-Term Site Productivity

    SciTech Connect (OSTI)

    Otrosina, W. J.; Garbelotto, M.

    1997-09-01

    Management activities and various land uses have taken place recently that have dramatically altered edaphic and environmental conditions under which forest tree species and ecosystems have evolved. Sequoia giganteum stands, fire suppression in this fire dependent ecosystem has resulted in increased mortality due to Heterobasidion annosum. On hypothesis is that fire suppression results in increased encroachment of true firs, easily infected by S-group Heterobasidion annosum, thereby transferring the disease via root contacts with S. giganteum. Existence of a hybrid with S and P ISG's of H. annosum may be evidence for anthropogenic influences on evolutionary pathways in this pathogen.

  18. Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

    DOE Patents [OSTI]

    Wright, Ernest M; Barrio, Jorge R; Hirayama, Bruce A; Kepe, Vladimir

    2014-09-30

    Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

  19. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    SciTech Connect (OSTI)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  20. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

    SciTech Connect (OSTI)

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; Pounds, Joel G.; Blackburn, Michael R.; Rodland, Karin D.; McDermott, Jason E.

    2013-10-01

    Background. The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective. To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods. The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC). Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results. The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions. Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.

  1. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Jiang, Pengtao; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 ; Huang, Zhen; Zhao, Hong; Wei, Taotao

    2013-04-19

    Highlights: •Free fatty acids exposure induces elevated autophagy. •H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. •Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-?, two typical “second hit” factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  2. Evolution of a genetic disease in an ethnic isolate:. beta. -Thalassemia in the Jews of Kurdistan

    SciTech Connect (OSTI)

    Rund, D.; Cohen, T.; Filon, D.; Rachmilewitz, E.; Oppenheim, A. ); Dowling, C.E.; Warren T.C.; Kazazian, H.H. Jr. ); Barak, I. )

    1991-01-01

    {beta}-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the {beta}-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of {beta}-thalassemia-the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered. Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews. The authors traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. They conclude that several evolutionary mechanisms contributed to the evolution of {beta}-thalassemia in this small ethnic isolate.

  3. Proteomic Analysis of Lyme Disease: Global Protein Comparison of Three Strains of Borrelia burgdorferi

    SciTech Connect (OSTI)

    Jacobs, Jon M.; Yang, Xiaohua; Luft, Benjamin J.; Dunn, John J.; Camp, David G.; Smith, Richard D.

    2005-04-01

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. It has been studied extensively to help understand its pathogenicity of infection and how it can persist in different mammalian hosts. We report the proteomic analysis of the archetype B. burgdorferi B31 strain and two other strains (ND40, and JD-1) having different Borrelia pathotypes using strong cation exchange fractionation of proteolytic peptides followed by high-resolution, reversed phase capillary liquid chromatography coupled with ion trap tandem mass spectrometric (LC-MS/MS) analysis. Protein identification was facilitated by the availability of the complete B31 genome sequence. A total of 665 Borrelia proteins were identified representing ~38 % coverage of the theoretical B31 proteome. A significant overlap was observed between the identified proteins in direct comparisons between any two strains (>72%), but distinct differences were observed among identified hypothetical and outer membrane proteins of the three strains. Such a concurrent proteomic overview of three Borrelia strains based upon only the B31 genome sequence is shown to provide significant insights into the presence or absence of specific proteins and a broad overall comparison among strains.

  4. Climate, Environmental, and Socioeconomic Change Weighing up the Balance in Vector-Borne Disease Transmission

    SciTech Connect (OSTI)

    Parham, Paul; Waldock, Johanna; Christophides, George; Hemming, Deborah; Agusto, Folashade; Evans, Katherine J; Fefferman, Nina; Gaff, Holly; Gumel, Abba; LaDeau, Shannon; Lenhart, Suzanne; Mickens, Ronald; Naumova, Elena; Ostfeld, Richard; Ready, Paul; Thomas, Matthew; Velasco-Hernandez, Jorge; Edwin, Michael

    2015-01-01

    Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is due not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but, perhaps most crucially, the multitude of epidemiological, ecological, and socioeconomic factors that drive VBD transmission, and this complexity has generated considerable debate over the last 10-15 years. In this article, and Theme Issue, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions, and, crucially, offer some solutions for the field moving forwards. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector-pathogen systems. This Theme Issue seeks to cover both, reflected in the breadth and depth of the topics and VBD-systems considered, itself strongly indicative of the challenging, but necessary, multidisciplinary nature of this research field.

  5. Iron and aluminum interaction with amyloid-beta peptides associated with Alzheimer’s disease

    SciTech Connect (OSTI)

    Drochioiu, Gabi; Ion, Laura; Murariu, Manuela; Habasescu, Laura

    2014-10-06

    An elevation in the concentration of heavy metal ions in Alzheimer’s disease (AD) brain has been demonstrated in many studies. A? precipitation and toxicity in AD brains seem to be caused by abnormal interactions with neocortical metal ions, especially iron, copper, zinc, and aluminum [1–3]. There is increasing evidence that iron and aluminum ions are involved in the mechanisms that underlie the neurodegenerative diseases [4,5]. However, evidence was brought to demonstrate that some A? fragments, at physiological pH, are not able to form binary complexes with Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation [6]. On the contrary, multiple metal ions are known to interact with A? peptides [7]. Consequently, we investigated here the interaction of Fe(II/III) and Al(III) ions with some amyloid-? peptides and fragments that results in peptide aggregation and fibrillation [8,9]. Infrared spectroscopy, atomic force microscopy, scanning electron microscopy, electrophoresis and mass spectrometry demonstrated conformational changes of peptides in the presence of such metals.

  6. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

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

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; et al

    2013-01-01

    Background . The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective . To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods . The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC).more » Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results . The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions . Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.« less

  7. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, Howard (Albany, CA); Kinney, John H. (Danville, CA); Otis, Linda L. (San Francisco, CA)

    1996-01-01

    A method for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces.

  8. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, H.; Kinney, J.H.; Otis, L.L.

    1996-10-29

    A method is disclosed for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces. 7 figs.

  9. Low Prevalence of Chronic Beryllium Disease among Workers at a Nuclear Weapons Research and Development Facility

    SciTech Connect (OSTI)

    Arjomandi, M; Seward, J P; Gotway, M B; Nishimura, S; Fulton, G P; Thundiyil, J; King, T E; Harber, P; Balmes, J R

    2010-01-11

    To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility. We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with HRCT (N=49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage (BAL) and transbronchial biopsies. The mean duration of employment at the facility was 18 yrs and the mean latency (from first possible exposure) to time of evaluation was 32 yrs. Five of the workers had CBD at the time of evaluation (based on histology or HRCT); three others had evidence of probable CBD. These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

  10. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOE Patents [OSTI]

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  11. DEVELOPMENT OF AUTOMATED SOFTWARE PROGRAM FOR THE ANALYSIS OF ALZHEIMER'S DISEASE BETA-AMYLOID SCANS

    SciTech Connect (OSTI)

    Mariotti, Jack; Zubal, George

    2013-12-18

    Study goal: A Phase 1 evaluation of the kinetics, clearance and cerebral distribution of one novel peripheral benzodiazepine receptors(PBR)positron emission tomography (PET) imaging agent, 18F-PBR-111 following intravenous administration in healthy volunteers and Alzheimer's disease (AD) patients. Short title: Evaluation of PET imaging with PBR-111 in HV and AD subjects Proof of Mechanism. Primary Objective: To evaluate the cerebral distribution of PBR-111 positron emission tomography (PET) for detection/exclusion of microglial activation in patients with Alzheimer's disease subjects compared to healthy volunteers. Secondary objectives: - To assess the dynamic uptake and washout of [18F]PBR-111, a potential imaging bio-marker for inflammatory changes in brain, using positron emission tomography in subjects with Alzheimer's disease (AD) and healthy volunteers (HV). - To perform blood metabolite characterization of [18F]PBR-111 in subjects with AD and HV to determine the nature of metabolites in assessment of [18F]-PBR-111 as a PET brain imaging agent. Name of radioactive drug substance: PBR-111 Dose(s): The applied PBR-111 radioactive dose will be up to 5.0 mCi, diluted in a maximum of 10 ml of saline. The radioligand will be administered as a slow intravenous bolus injection (i.e., 6 sec/ml) into a large vein (e.g., antecubital vein). Route of administration: Intravenous injection Duration of treatment: Single administration of a diagnostic agent Indication: PBR-111 positron emission tomography (PET) imaging has the potential to detect microglial activation. In the presence of PBR-111 uptake (representative of microglial activation), inflammation in the brain can be detected. Diagnosis and main criteria for inclusion: Study participants will be HVs and patients diagnosed with probable AD. HVs must be 18 years of age (at least four subjects 50 years of age) and have no evidence of cognitive impairment or other neurologic disease by medical history. The lack of cognitive impairment will also be based on a Clinical Dementia Rating (CDR) of 0. Patients with probable AD must be 50 years of age and must fulfill the National Institute of Neurological and Communicative Disorders and Stroke, Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA] criteria for probable AD. The CDR score must be 1.0 and 2.0 and have a modified Hachinski of 4. All HVs and all patients with probable AD must be able to comply with all study procedures. Study design: This is a Phase 1, open-label, single-center, non-randomized single dose study to assess the kinetics, clearance and cerebral distribution of PBR-111 PET imaging in detecting microglial activation in the brain in patients with probable AD compared to HVs. All aspects related to image acquisition, processing, and visual as well as quantitative evaluation will be developed, optimized, and validated (where required). Each subject will be required to visit the study center during the screening phase and on the PBR-111 PET imaging day (baseline). A telephone follow-up visit will be performed 7 days (± 3 days) after PBR-111 PET administration. At the screening visit, each subject (or caregiver in the case of AD subjects) will be asked to provide written informed consent or assent. During the screening phase (maximum duration of 60 days) subject medical, neurological, and surgical history, clinical assessments, and a neuro-psychiatric evaluation will be performed on all eligible subjects. Subjects will be allowed to leave the center after all evaluations have been completed. During this period an MRI of the brain will be performed during the screening period. If an MRI of the brain has been performed within six months of the imaging visit using the methods described in the protocol, and there has been no medically significant events in the interim, the previous MRI may be used. During the PBR-111 PET imaging day, all subjects will receive a single intravenous injection of PBR-111 and scanning will be performed over a 3.5 hour period. Each subject will have a telephone follow-up 7 days (± 3 days) thereafter to assess for adverse events. Methodology: - Assessments to provide clinical characterization of the AD subjects will be performed. - After administration of PBR-111, images will be generated with state-of-the-art PET imaging. Images will be assessed quantitatively for the presence of microglial activation by a nuclear physician blinded to clinical data. - Total radioactivity and estimation of the fraction of radioactivity associated to the un-metabolized tracer will be determined. In addition, the metabolite patterns of PBR-111 are determined in venous plasma and arterial samples based on high-performance liquid chromatography (HPLC) analyses. - Arterial sampling will be acquired in the initial two AD and two HV subjects and modeling will be assessed to determine if additional arterial sampling is necessary.

  12. Nanoimaging to Prevent and Treat Alzheimer’s and Parkinson’s Diseases. Scientific/Technical report

    SciTech Connect (OSTI)

    Yuri L. Lyubchenko, PhD, DSc

    2012-12-20

    This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimer’s, Parkinson’s and Huntington’s diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimer’s and Parkinson’s diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establish an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.

  13. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    SciTech Connect (OSTI)

    Skinner, F. K.; Department of Medicine , University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8 ; Ferguson, K. A.; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  14. Structure of the Newcastle disease virus F protein in the post-fusion conformation

    SciTech Connect (OSTI)

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.; Paterson, Reay G.; Lamb, Robert A.; Jardetzky, Theodore S. (Stanford-MED); (NWU); (HHMI)

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure contains heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.

  15. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

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

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individualmore » pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.« less

  16. Similarities of host defense mechanisms against pulmonary infectious disease in animals and man

    SciTech Connect (OSTI)

    Green, G.M.

    1984-01-01

    Evidence linking exposure to air pollutants with increased susceptibility to infectious diseases in humans comes from epidemiological, clinical, and experimental laboratory studies. The data suggest that the most common, and perhaps the most sensitive, index of the pulmonary effect of air pollutant exposure is on post upper respiratory infection, prolonged cough, phlegm, and purulent sputum. Experimental models of these relationships for extrapolation to humans should be able to measure such minor changes in symptomatology and physiology rather than require major lethal events. The bacterial aerosol model for quantifying nonspecific defense mechanisms of the bronchopulmonary tree utilizing nonpathogenic organisms fulfills this criterion. The function of the six major components of pulmonary antimicrobial defense mechanisms - including aerodynamic filtration, secretory respiratory tract fluid, fluid transport at the alveolar and bronchial levels, the phagocytic function of alveolar macrophages, the augmenting mechanisms of blood-derived inflammatory cells, and the secretory and cellular-specific immune mechanisms and their mediator products - can all be quantified by this experimental animal model system. The defensive functions are remarkably similar across animal species, and available human data suggest that findings obtained using the model may be extrapolatred to humans.

  17. Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease

    SciTech Connect (OSTI)

    Rossi, Michele; Iezzi, Roberto

    2013-11-06

    PurposeThese guidelines are intended for use in assessing the standard for technical success and safety in aorto-iliac percutaneous endovascular interventions.MethodsAny recommendation contained in the text comes from the highest level and extension of literature review available to date.ResultsThe success of endovascular procedures is strictly related to an accurate planning based mainly on CT- or MR-angiography. TASC II A through C lesions have an endovascular-first option Pre-procedure ASA antiplatelet therapy is advisable in all cases. The application of stents improves the immediate hemodynamic and most likely long-term clinical results. Cumulative mean complication rate is 7.51 % according to the most relevant literature. Most of the complications can be managed by means of percutaneous techniques.ConclusionThe design and quality of devices, as well as the easy and accuracy of performing these procedures, have improved over the last decades, leading to the preferential treatment of aorto-iliac steno-obstructive disease via endovascular means, often as first-line therapy, with high technical success rate and low morbidity. This is mirrored by the decreasing number of patients undergoing surgical grafts over the last years with patency, limb salvage, and survival rates equivalent to open reconstruction.

  18. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell Carcinoma—A TROG Substudy

    SciTech Connect (OSTI)

    Finnigan, Renee; Hruby, George; Wratten, Chris; Keller, Jacqui; Tripcony, Lee; Dickie, Graeme; Rischin, Danny; Poulsen, Michael

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  19. Memorandum, Clarification of Title 10 of the Code of Federal Regulations, Part 850 (10 CPR 850), Chronic Beryllium Disease Prevention Program, Paragraph 850.34(g)

    Broader source: Energy.gov [DOE]

    The purpose of this memorandum is to clarification regarding the reporting of beryllium sensitization (BeS) and chronic beryllium disease (CBD) as required by paragraph 850.34(g) of the Chronic Beryllium Disease Prevention Program rule (10 CFR 850).

  20. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

    SciTech Connect (OSTI)

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (A?) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of A? pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of A? pores. The fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the A? pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to A? pores and show that the extent and spatial range of such up-regulation increases as A? pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.

  1. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect (OSTI)

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  2. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    SciTech Connect (OSTI)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; Moulder, John E.; Baker, John E.

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  3. Fourier Transform Infrared Imaging Showing Reduced Unsaturated Lipid Content in the Hippocampus of a mouse Model of Alzheimer's Disease

    SciTech Connect (OSTI)

    Leskovjan, A.C.; Kretlow, A.; Miller, L.M.

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic {double_bond}CH stretching mode at 3012 cm{sup -1}. The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p < 0.01) but remained low and relatively constant in PSAPP mice. Thus, these findings indicate that unsaturated lipid content is reduced in hippocampal white matter during amyloid pathogenesis and that maintaining unsaturated lipid content early in the disease may be critical in avoiding progression of the disease.

  4. Percutaneous Transsplenic Access to the Portal Vein for Management of Vascular Complication in Patients with Chronic Liver Disease

    SciTech Connect (OSTI)

    Chu, Hee Ho; Kim, Hyo-Cheol Jae, Hwan Jun; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Chung, Jin Wook; Park, Jae Hyung

    2012-12-15

    Purpose: To evaluate the safety and feasibility of percutaneous transsplenic access to the portal vein for management of vascular complication in patients with chronic liver diseases. Methods: Between Sept 2009 and April 2011, percutaneous transsplenic access to the portal vein was attempted in nine patients with chronic liver disease. Splenic vein puncture was performed under ultrasonographic guidance with a Chiba needle, followed by introduction of a 4 to 9F sheath. Four patients with hematemesis or hematochezia underwent variceal embolization. Another two patients underwent portosystemic shunt embolization in order to improve portal venous blood flow. Portal vein recanalization was attempted in three patients with a transplanted liver. The percutaneous transsplenic access site was closed using coils and glue. Results: Percutaneous transsplenic splenic vein catheterization was performed successfully in all patients. Gastric or jejunal varix embolization with glue and lipiodol mixture was performed successfully in four patients. In two patients with a massive portosystemic shunt, embolization of the shunting vessel with a vascular plug, microcoils, glue, and lipiodol mixture was achieved successfully. Portal vein recanalization was attempted in three patients with a transplanted liver; however, only one patient was treated successfully. Complete closure of the percutaneous transsplenic tract was achieved using coils and glue without bleeding complication in all patients. Conclusion: Percutaneous transsplenic access to the portal vein can be an alternative route for portography and further endovascular management in patients for whom conventional approaches are difficult or impossible.

  5. Understanding the chemical properties of macerals and minerals in coal and its potential application for occupational lung disease prevention

    SciTech Connect (OSTI)

    Huang, X.; Finkelman, R.B.

    2008-07-01

    The objective of this review was to assess whether some chemical parameters in coal play a role in producing environmental health problems. Basic properties of coal - such as chemical forms of the organic materials, structure, compositions of minerals - vary from one coal mine region to another as well as from coals of different ranks. Most importantly, changes in chemical properties of coals due to exposure to air and humidity after mining - a dynamic process - significantly affect toxicity attributed to coal and environmental fate. Although coal is an extremely complex and heterogeneous material, the fundamental properties of coal responsible for environmental and adverse health problems are probably related to the same inducing components of coal. For instance, oxidation of pyrite (FeS{sub 2}) in the coal forms iron sulfate and sulfuric acid, which produces occupational lung diseases (e.g., pneumoconiosis) and other environmental problems (e.g., acid mine drainage and acid rain). Calcite (CaCO{sub 3}) contained in certain coals alters the end products of pyrite oxidation, which may make these coals less toxic to human inhalation and less hazardous to environmental pollution. Finally, knowledge gained on understanding of the chemical properties of coals is illustrated to apply for prediction of toxicity due to coal possibly before large-scale mining and prevention of occupational lung disease during mining.

  6. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

  7. Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel

    SciTech Connect (OSTI)

    Goren, A.I.; Hellmann, S.

    1988-02-01

    Second and fifth grade schoolchildren living in two communities with different levels of air pollution were studied. The parents of these children filled out ATS-NHLI health questionnaires. The prevalence of reported respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted community (Ashdod) as compared with the low-pollution area (Hadera). Logistic models fitted for the respiratory conditions which differed significantly between both areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.47 for cough without cold to 2.66 for asthma for children from Ashdod, as compared with 1.00 for children from Hadera.

  8. Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study

    SciTech Connect (OSTI)

    Holmes, Jordan A.; Wang, Andrew Z.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Hoffman, Karen E.; Hendrix, Laura H.; Rosenman, Julian G.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Carpenter, William R.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Health Policy and Management, University of North Carolina School of Public Health, Chapel Hill, NC ; Godley, Paul A.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Division of Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC ; Chen, Ronald C.

    2012-09-01

    Purpose: To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. Methods and Materials: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as the highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. Results: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. Conclusions: There may be underutilization of RT in older prostate cancer patients and those with likely extraprostatic disease. Because more than half of prostate cancer patients do not consult with a radiation oncologist, a multidisciplinary consultation may affect the treatment decision-making process.

  9. The effects of total dissolved gas on chum salmon fry survival, growth, gas bubble disease, and seawater tolerance

    SciTech Connect (OSTI)

    Geist, David R.; Linley, Timothy J.; Cullinan, Valerie I.; Deng, Zhiqun

    2013-02-01

    Chum salmon Oncorhynchus keta alevin developing in gravel habitats downstream of Bonneville Dam on the Columbia River are exposed to elevated levels of total dissolved gas (TDG) when water is spilled at the dam to move migrating salmon smolts downstream to the Pacific Ocean. Current water quality criteria for the management of dissolved gas in dam tailwaters were developed primarily to protect salmonid smolts and are assumed to be protective of alevin if adequate depth compensation is provided. We studied whether chum salmon alevin exposed to six levels of dissolved gas ranging from 100% to 130% TDG at three development periods between hatch and emergence (hereafter early, middle, and late stage) suffered differential mortality, growth, gas bubble disease, or seawater tolerance. Each life stage was exposed for 50 d (early stage), 29 d (middle stage), or 16 d (late stage) beginning at 13, 34, and 37 d post-hatch, respectively, through 50% emergence. The mortality for all stages from exposure to emergence was estimated to be 8% (95% confidence interval (CI) of 4% to 12%) when dissolved gas levels were between 100% and 117% TDG. Mortality significantly increased as dissolved gas levels rose above 117% TDG,; with the lethal concentration that produced 50% mortality (LC50 ) was estimated to be 128.7% TDG (95% CI of 127.2% to 130.2% TDG) in the early and middle stages. By contrast, there was no evidence that dissolved gas level significantly affected growth in any life stage except that the mean wet weight at emergence of early stage fish exposed to 130% TDG was significantly less than the modeled growth of unexposed fish. The proportion of fish afflicted with gas bubble disease increased with increasing gas concentrations and occurred most commonly in the nares and gastrointestinal tract. Early stage fish exhibited higher ratios of filament to lamellar gill chloride cells than late stage fish, and these ratios increased and decreased for early and late stage fish, respectively, as gas levels increased; however, there were no significant differences in mortality between life stages after 96 h in seawater. The study results suggest that current water quality guidelines for the management of dissolved gas appear to offer a conservative level of protection to chum salmon alevin incubating in gravel habitat downstream of Bonneville Dam.

  10. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect (OSTI)

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  11. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect (OSTI)

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  12. Review of Monitoring Plans for Gas Bubble Disease Signs and Gas Supersaturation Levels on the Columbia and Snake Rivers.

    SciTech Connect (OSTI)

    Fidler, Larry; Elston, Ralph; Colt, John

    1994-07-01

    Montgomery Watson was retained by the Bonneville Power Administration to evaluate the monitoring program for gas bubble disease signs and dissolved gas supersaturation levels on the Columbia and Snake rivers. The results of this evaluation will provide the basis for improving protocols and procedures for future monitoring efforts. Key study team members were Dr. John Colt, Dr. Larry Fidler, and Dr. Ralph Elston. On the week of June 6 through 10, 1994 the study team visited eight monitoring sites (smolt, adult, and resident fish) on the Columbia and Snake rivers. Additional protocol evaluations were conducted at the Willard Field Station (National Biological Survey) and Pacific Northwest Laboratories at Richland (Battelle). On June 13 and 14, 1994, the study team visited the North Pacific Division office of the U.S. Corps of Engineers and the Fish Passage Center to collect additional information and data on the monitoring programs. Considering the speed at which the Gas Bubble Trauma Monitoring Program was implemented this year, the Fish Passage Center and cooperating Federal, State, and Tribal Agencies have been doing an incredible job. Thirty-one specific recommendations are presented in this report and are summarized in Section 14.

  13. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-02-06

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure vari-ations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagran-gian tracking approach were used to model respiratory airflows and aerosol dynamics. Respira-tions of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug de-livery protocol.

  14. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang [Central Michigan Univ., Mount Pleasant, MI (United States); Kim, JongWon [Central Michigan Univ., Mount Pleasant, MI (United States); Si, Xiuhua A. [California Baptist Univ., Riverside, CA (United States); Corley, Richard A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kabilan, Senthil [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Shengyu [First Affiliated Hospital of Xi'an Medical Univ., Shaanxi (China); Mayo Clinic, Rochester, MN (United States)

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 ?m at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  15. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

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

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treatmore » the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.« less

  16. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Chen, Qiang; The First Affiliated Hospital of Xiamen University, Xiamen ; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  17. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

    SciTech Connect (OSTI)

    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. ); George, J.F. ); Goodenow, M.M. Univ. of Alabama, Birmingham, AL )

    1994-07-01

    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  18. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2?) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2? levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect (OSTI)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause the adaptive change of glucocorticoid-IGF1 axis.

  20. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    SciTech Connect (OSTI)

    Atalar, Banu; Modlin, Leslie A.; Choi, Clara Y.H.; Adler, John R.; Gibbs, Iris C.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Nagpal, Seema; Hanlon, Alexandra; Soltys, Scott G.

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  1. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect (OSTI)

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses (which are of two bovine types) bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). A timeline for this development is presented in Table 1. The development of the Version 1.0 panel for FMDV rule-out and the most current efforts aimed to designed species specific panels has spanned over 2 1/2 years with multiple collaborative partnerships. This document provides a summary of the development, testing and performance data at OIE Stage 1 Feasibility into Stage 2 Assay Development and Standardization1 (see Table 2), gathered as of June 30th, 2007 for the porcine and bovine MUX assay panels. We present an overview of the identification and selection of candidate genetic signatures, the assay development process, and preliminary performance data for each of the individual signatures as characterized in the multiplexed format for the porcine and bovine panels. The Stage 1 Feasibility data of the multiplexed panels is presented in this report also includes relevant data acquired from the Version 1.0 panel as supporting information where appropriate. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must precede efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available. As a summary report, this document does not provide the details of signature generation, evaluation, and testing, nor does it provide spec

  2. Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; Anchel, David J.; Gaudette, Glenn; Romanelli, Pantaleo; Hainfeld, James

    2010-06-29

    A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

  3. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

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

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; et al

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  4. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  5. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect (OSTI)

    Feddock, Jonathan; Arnold, Susanne M.; Department of Medical Oncology, University of Kentucky, Lexington, Kentucky ; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (?5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ?3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  6. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

    SciTech Connect (OSTI)

    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F.

    1994-09-01

    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  7. Enhanced vector borne disease surveillance of California Culex mosquito populations reveals spatial and species-specific barriers of infection.

    SciTech Connect (OSTI)

    VanderNoot, Victoria A.; Curtis, Deanna Joy; Koh, Chung-Yan; Brodsky, Benjamin H; Lane, Todd

    2014-08-01

    Monitor i ng in f ectio n s in v ect o rs su c h as m osquit o es, s a nd fl i es, tsetse fl i es, a nd ticks to i denti f y hu m a n path o gens m a y s e r v e as a n ear l y w arn i ng det e ction system t o dir e ct loc a l g o v er n ment dise a se pr e v en t i v e m easu r e s . One major hurdle i n de t ection is the abi l i t y to scre e n l arge n u mbers of v e c t ors for h uman patho g ens w i thout t h e u s e of ge n o t y pe - s p ecific m o lecu l ar tec h nique s . N e x t genera t ion s equ e nc i ng (NG S ) pr o v i des a n unbi a sed p latfo r m capab l e of identi f y i ng k n o w n a n d unk n o w n p ath o ge n s circula t ing w i thin a v e ctor p opul a tion, but utili z ing t h is te c h nolo g y i s tim e - con s u ming a n d cos t l y for v ecto r -b o rne disease su r v e illan c e pr o gra m s. T o addr e s s this w e d e v e lop e d cos t -eff e ct i v e Ilumina(r) R NA- S eq l i bra r y p r epara t ion m e thodol o gies i n con j u n ction w i t h an automa t ed c ompu t at i onal a n a l y sis pipel i n e to ch a racter i ze t h e microbial popula t ions c ircula t i n g in Cu l e x m o squit o e s (Cul e x qui n quef a s c iatu s , C ul e x quinq u efasc i atus / pip i ens co m pl e x h y bri d s, and C u l e x ta r salis ) t hroug h out Californ i a. W e assembled 2 0 n o vel a n d w e l l -do c ume n ted a r b o v i ruses repres e nting mem b e rs of B u n y a v ir i da e , F l a v i virid a e, If a virida e , Meson i v i rida e , Nid o v iri d ae, O rtho m y x o virid a e, Pa r v o v iri d ae, Re o virid a e, R h a b d o v i rid a e, T y m o v iri d ae, a s w ell as s e v e r al u n assi g n e d v irus e s . In addit i o n, w e m app e d mRNA s pecies to d i vergent s peci e s of t r y panos o ma a nd pl a s modium eu k a r yotic parasit e s and cha r a c terized t he p r oka r yot i c microb i al c o mposit i on to i d enti f y bacteri a l tran s c r ipts der i v ed from wolba c hia, clo s tridi u m, m y c oplas m a, fusoba c terium and c am p y l o bacter bac t er i al spec i e s . W e utilized the s e mic r obial transcri p tomes pre s e nt in g e ogra p hical l y defined Cul e x po p ul a tions to defi n e spatial and m osqui t o specie s -spec i fic ba r r iers of i n fecti o n. T he v i r ome and microbi o me c o mpos i tion id e ntified in e ach mosqui t o p o ol pr o v i ded suf f icient resolut i on to dete r m i ne both the mosq u ito species and the g e o graphic regi o n in Californ i a w h e re t h e mosqui t o po o l orig i n ated. T his d a ta pr o v i des ins i ght in t o the compl e x i t y of microb i al spec i es cir c ulati n g in med i cal l y i mport a nt Culex mosqui t oes a nd t h eir potent i al im p act o n t he tran s missi o n of v ector-b o rne human / veter i na r y p a t hogens in C a liforn i a.

  8. A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

    SciTech Connect (OSTI)

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N. . E-mail: j@andreyev.demon.co.uk

    2006-04-01

    Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

  9. A radiation hybrid map of the distal short arm of human chromosome II, containing the Beckwith-Weidemann and associated embroyonal tumor disease loci

    SciTech Connect (OSTI)

    Richard, C.W. III; Berg, D.J.; Meeker, T.C.; Myers, R.M.; Cox, D.R. ); Boehnke, M.; Hauser, E. ); Lichy, J.H. )

    1993-05-01

    The authors describe a high-resolution radiation hybrid (RH) map of the distal short arm of human chromosome 11 containing the Beckwith-Weidemann gene and the associated embryonal tumor disease loci. Thirteen human 11p15 genes and 17 new anonymous probes were mapped by a statistical analysis of the cosegregation of markers in 102 rodent-human radiation hybrids retaining fragments of human chromosome 11. The 17 anonymous probes were generated from lambda phage containing human 11p15.5 inserts, by using ALU-PCR. A comprehensive map of all 30 loci and a framework map of nine clusters of loci ordered at odds of 1,000:1 were constructed by a multipoint maximum-likelihood approach by using the computer program RHMAP. This RH map localizes one new gene to chromosome 11p15 (WEE1), provides more precise order information for several 11p15 genes (CTSD, H19, HPX,.ST5, RNH, and SMPD1), confirms previous map orders for other 11p15 genes (CALCA, PTH, HBBC, TH, HRAS, and DRD4), and maps 17 new anonymous probes within the 11p15.5 region. This RH map should prove useful in better defining the positions of the Beckwith-Weidemann and associated embryonal tumor disease-gene loci. 41 refs., 1 fig., 2 tabs.

  10. Update to agency for toxic substances and disease registry 2012 report on assessment of biota exposure to mercury originating from Savannah River Site.

    SciTech Connect (OSTI)

    Kuhne, W.

    2015-08-10

    The purpose of this report is to 1) update previous Savannah River National Laboratory (SRNL) assessment reports (Kvartek et al. 1994 and Halverson et al. 2008) on the fate of mercury in the Savannah River Site (SRS) environment and 2) address comments and recommendations from the review of SRS by the Agency for Toxic Substances and Disease Registry (ATSDR) concerning the evaluation of exposures to contaminants in biota originating from the SRS. The ATSDR reviewed and evaluated data from SRS, South Carolina Department of Health & Environmental Control (SCDHEC) and the Georgia Department of Natural Resources (GDNR) concerning the non-radioactive contaminant mercury. This report will provide a response and update to conclusions and recommendations made by the ATSDR.

  11. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington's disease

    SciTech Connect (OSTI)

    Zuleta, Amparo [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Vidal, Rene L. [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Neurounion Biomedical Foundation, Santiago (Chile); Armentano, Donna; Parsons, Geoffrey [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)] [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Hetz, Claudio, E-mail: chetz@med.uchile.cl [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Av., Boston, MA 02446 (United States); Neurounion Biomedical Foundation, Santiago (Chile)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer The contribution of ER stress to HD has not been directly addressed. Black-Right-Pointing-Pointer Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. Black-Right-Pointing-Pointer We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington's disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588{sup Q95}-mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588{sup Q95}-mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  12. Impact of Preoperative Radiotherapy on General and Disease-Specific Health Status of Rectal Cancer Survivors: A Population-Based Study

    SciTech Connect (OSTI)

    Thong, Melissa S.Y., E-mail: M.Thong@uvt.nl [Center of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University (Netherlands); Comprehensive Cancer Centre South, Eindhoven (Netherlands); Mols, Floortje [Center of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University (Netherlands); Comprehensive Cancer Centre South, Eindhoven (Netherlands); Lemmens, Valery E.P.P. [Comprehensive Cancer Centre South, Eindhoven (Netherlands); Department of Public Health, Erasmus University Medical Centre, Rotterdam (Netherlands); Rutten, Harm J.T. [Department of Surgery, Catharina Hospital, Eindhoven (Netherlands); Roukema, Jan A. [Department of Surgery, St. Elisabeth Hospital, Tilburg (Netherlands); Martijn, Hendrik [Department of Radiotherapy, Catharina Hospital, Eindhoven (Netherlands); Poll-Franse, Lonneke V. van de [Center of Research on Psychology in Somatic Diseases (CoRPS), Tilburg University (Netherlands); Comprehensive Cancer Centre South, Eindhoven (Netherlands)

    2011-11-01

    Purpose: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years postdiagnosis. The health status of older ({>=}75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. Methods and Materials: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. Results: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term ({>=}5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. Conclusions: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.

  13. Enhanced sensitivity and specificity of thallium-201 imaging for the detection of regional ischemic coronary disease by combining SPECT with bull's eye analysis

    SciTech Connect (OSTI)

    Kasabali, B.; Woodard, M.L.; Bekerman, C.; Pinsky, S.; Blend, M.J. (Michael Reese Hospital and Medical Center, Chicago, IL (USA))

    1989-07-01

    Previous studies have indicated that the combination of single photon emission computed tomography (SPECT) and quantitative bull's eye analysis (QBA) TI-201 cardiac stress imaging may improve the detection of myocardial ischemia over that achieved with planar (PLN) imaging. This study will evaluate the sensitivity and specificity of SPECT and QBA in the detection of disease in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery. Ninety-nine patients who underwent both TI-201 stress imaging and coronary arteriography were evaluated retrospectively. Of the 99, 62 had PLN imaging and 37 were evaluated with SPECT; 23 of these 37 had QBA. The overall sensitivity and specificity were as follows: PLN, 94% and 50%; SPECT, 90% and 67%; QBA, 100% and 20%; and SPECT with QBA, 92% and 72%, respectively. The regional sensitivity and specificity of PLN for individual coronary arteries were as follows: RCA, 78% and 74%; LAD, 89% and 60%; LCX, 50% and 89%, respectively. For SPECT, the results were: RCA, 86% and 93%; LAD, 85% and 88%; and LCX, 60% and 88%. For QBA alone, the results were: RCA, 100% and 75%; LAD, 88% and 53%; and LCX, 100% and 89%. The results for QBA with SPECT were: RCA, 100% and 94%; LAD, 88% and 80%; and LCX, 67% and 95%. Thus, SPECT interpreted on conjunction with QBA showed higher sensitivity for evaluation of ischemia in the RCA and LCX arteries and higher specificity in the detection of LAD and RCA disease than did PLN TI-201 imaging. Because of the low specificity of QBA (20%), caution is advised in the interpretation of QBA alone without reviewing SPECT images.

  14. Whole Abdominopelvic Radiotherapy Using Intensity-Modulated Arc Therapy in the Palliative Treatment of Chemotherapy-Resistant Ovarian Cancer With Bulky Peritoneal Disease: A Single-Institution Experience

    SciTech Connect (OSTI)

    De Meerleer, Gert; Vandecasteele, Katrien; Ost, Piet; Delrue, Louke; Denys, Hannelore; Makar, Amin; Speleers, Bruno; Van Belle, Simon; Van den Broecke, Rudy; Fonteyne, Valerie; De Neve, Wilfried

    2011-03-01

    Purpose: To retrospectively review our experience with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease. Methods and Materials: Between April 2002 and April 2008, 13 patients were treated with WAPRT using intensity-modulated arc therapy. We prescribed a dose of 33 Gy to be delivered in 22 fractions of 1.5 Gy to the abdomen and pelvis. All patients had International Federation of Gynecology and Obstetrics Stage III or IV ovarian cancer at the initial diagnosis. At referral, the median age was 61 years, and the patients had been heavily pretreated with surgery and chemotherapy. All patients had symptoms from their disease, including gastrointestinal obstruction or subobstruction in 6, minor gastrointestinal symptoms in 2, pain in 4, ascites in 1, and vaginal bleeding in 2. A complete symptom or biochemical response required complete resolution of the patient's symptoms or cancer antigen-125 level. A partial response required {>=}50% resolution of these parameters. The actuarial survival was calculated from the start of radiotherapy. Results: The median overall survival was 21 weeks, with a 6-month overall survival rate of 45%. The 9 patients who completed treatment obtained a complete symptom response, except for ascites (partial response). The median and mean response duration (all symptoms grouped) was 24 and 37 weeks, respectively. Of the 6 patients presenting with obstruction or subobstruction, 4 obtained a complete symptom response (median duration, 16 weeks). Conclusion: WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

  15. Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

    SciTech Connect (OSTI)

    Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W.; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J.

    2013-04-01

    Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.

  16. Enter filename

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

    sources, prenatal radiation exposure, maternal or child medications, pesticides, second-hand cigarette smoke, factors associated with maternal pregnancy history (maternal age...

  17. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect (OSTI)

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses which are of two bovine types bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). This document provides details of signature generation, evaluation, and testing, as well as the specific methods and materials used. A condensed summary of the development, testing and performance of the multiplexed assay panel was presented in a 126 page separate document, entitled 'Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out'. This supplemental document provides additional details of large amount of data collected for signature generation, evaluation, and testing, as well as the specific methods and materials used for all steps in the assay development and utilization processes. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, VSV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must preceed efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available.

  18. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect (OSTI)

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival.

  19. Using Wikipedia to forecast diseases

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

    based on today's forecast." Del Valle and her team were able to successfully monitor influenza in the United States, Poland, Japan and Thailand, dengue fever in Brazil and...

  20. Using Wikipedia to forecast disease

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

    to plan for future outbreaks. The LANL team was able to successfully monitor influenza in the United States, dengue fever in Brazil and Thailand, and tuberculosis in China...

  1. Fridges to fight childhood disease

    SciTech Connect (OSTI)

    Lerner, T.

    1983-04-01

    A solar-powered refrigerator/freezer has been installed in a medical center in Bhoorbaral, India. The installation and performance of the refrigerator/freezer are described.

  2. 1

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

    implant and other applications. Orthopedic device makers typically use chemical etching, bead blasting, or coatings to roughen the metal surface to create smaller-scale...

  3. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect (OSTI)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: choo.c@mayo.edu; Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON (Canada); Pearse, Maria [Department of Radiation Oncology, Auckland Hospital, Auckland (New Zealand)

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  4. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    SciTech Connect (OSTI)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. )

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

  5. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood

    SciTech Connect (OSTI)

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N.; Mastorodemos, Vasileios; Plaitakis, Andreas; Tsatsakis, Aristidis M.

    2011-11-15

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD + opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 {mu}g/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. -- Highlights: Black-Right-Pointing-Pointer Exposure to pesticides and organic solvents might be a risk factor for sporadic MND. Black-Right-Pointing-Pointer We report a patient who developed progressive upper and lower motor neuron disease. Black-Right-Pointing-Pointer The patient had a history of occupational exposure to pesticides and solvents. Black-Right-Pointing-Pointer High DDTs' levels and increased levels of DMP and DEP were measured in his hair. Black-Right-Pointing-Pointer The patients' exposure to chemicals might have played a role in MND development.

  6. Protein Instability and Lou Gehrig's Disease

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

    Amyotrophic lateral sclerosis is notorious for its ability to strike down people in the prime of life. It first leapt into public consciousness when it afflicted baseball star...

  7. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    Todd DeSantis

    2010-01-08

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  8. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    DeSantis, Todd

    2009-01-01

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  9. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    Todd DeSantis

    2009-01-30

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  10. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    DeSantis, Todd

    2013-05-29

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  11. "Artificial" brains, electrical grids, and disease modeling:...

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

    Deputy Principal Associate Director Duncan McBranch will discuss LDRD impacts on border security and the nation's energy grid at 1 p.m. The event is an ideal opportunity...

  12. Protein Instability and Lou Gehrig's Disease

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

    more prone to form clusters or aggregates, suggesting that strategies for stabilizing SOD proteins could be useful in treating or preventing SOD-linked ALS. The Other ALS...

  13. Protein Instability and Lou Gehrig's Disease

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

    Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins...

  14. OCT for diagnosis of periodontal disease

    SciTech Connect (OSTI)

    Colston, B.W., LLNL

    1998-01-01

    We have developed a hand-held in vivo scanning device for use in the oral cavity. We produced, using this scanning device, in vivo OCT images of dental tissues in human volunteers. All the OCT images were analyzed for the presence of clinically relevant anatomical structures. The gingival margin, periodontal sulcus, and dento-enamel junction were visible in all the images. The cemento-enamel junction was discernible in 64% of the images and the alveolar bone presumptively identified for 71% of the images. These images represent, to our knowledge, the first in vivo OCT images of human dental tissue.

  15. Chronic Beryllium Disease Prevention Program What's New

    Broader source: Energy.gov [DOE]

    For additional information Contact: David Weitzman, Office of Worker Safety and Health Policy at (301) 903-5401 or: David.Weitzman@hq.doe.gov.

  16. Poster — Thur Eve — 03: Application of the non-negative matrix factorization technique to [{sup 11}C]-DTBZ dynamic PET data for the early detection of Parkinson's disease

    SciTech Connect (OSTI)

    Lee, Dong-Chang; Jans, Hans; McEwan, Sandy; Riauka, Terence; Martin, Wayne; Wieler, Marguerite

    2014-08-15

    In this work, a class of non-negative matrix factorization (NMF) technique known as alternating non-negative least squares, combined with the projected gradient method, is used to analyze twenty-five [{sup 11}C]-DTBZ dynamic PET/CT brain data. For each subject, a two-factor model is assumed and two factors representing the striatum (factor 1) and the non-striatum (factor 2) tissues are extracted using the proposed NMF technique and commercially available factor analysis software “Pixies”. The extracted factor 1 and 2 curves represent the binding site of the radiotracer and describe the uptake and clearance of the radiotracer by soft tissues in the brain, respectively. The proposed NMF technique uses prior information about the dynamic data to obtain sample time-activity curves representing the striatum and the non-striatum tissues. These curves are then used for “warm” starting the optimization. Factor solutions from the two methods are compared graphically and quantitatively. In healthy subjects, radiotracer uptake by factors 1 and 2 are approximately 35–40% and 60–65%, respectively. The solutions are also used to develop a factor-based metric for the detection of early, untreated Parkinson's disease. The metric stratifies healthy subjects from suspected Parkinson's patients (based on the graphical method). The analysis shows that both techniques produce comparable results with similar computational time. The “semi-automatic” approach used by the NMF technique allows clinicians to manually set a starting condition for “warm” starting the optimization in order to facilitate control and efficient interaction with the data.

  17. Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

    SciTech Connect (OSTI)

    Nakajima, Naomi; Kataoka, Masaaki; Sugawara, Yoshifumi; Ochi, Takashi; Kiyoto, Sachiko; Ohsumi, Shozo; Mochizuki, Teruhito

    2013-11-15

    Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients. Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (?53.1; n=8; P<.0001, log–rank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ?53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has potential benefits to identify a subgroup at higher risk for recurrence.

  18. HOPM1 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang (Okemos, MI); Nomura, Kinya (East Lansing, MI)

    2011-11-15

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein HopM1.sub.1-300 mediated protection is enhanced, such as increased protection to Pseudomonas syringae pv. tomato DC3000 HopM1 and/or there is an increase in activity of an ATMIN associated plant protection protein, such as ATMIN7. Reagents of the present invention further provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  19. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J. (Oakland, CA); Vogel, John S. (San Jose, CA); Fitzgerald, Robert L. (Encinitas, CA); Deftos, Leonard J. (Del Mar, CA); Herold, David (Del Mar, CA); Burton, Douglas W. (San Diego, CA)

    2012-05-15

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  20. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2013-03-05

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  1. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, R.M.; Blanche, P.J.; Orr, J.

    1999-07-20

    A variable rate density gradient electrophoric gel is described which separates LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described. 8 figs.

  2. Methods of treating Parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys; Cunningham, Janet

    2012-11-13

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the central nervous system (CNS) are provided for the treatment of CNS disorders, particularly those disorders which involve the neurotransmitter dopamine. The methods entail providing rAAV virions that comprise a transgene encoding aromatic amino acid decarboxylase (AADC) and administering the virions to the brain of a mammal using a non-manual pump.

  3. disease outbreak. Brozik, Susan Marie; Manginell, Ronald Paul...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  4. ORISE Research Participation Programs at the Centers for Disease...

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

    Dr. Feng Liu Research Profile - Dr. Feng Liu Dr. Feng Liu performed research on influenza vaccines with the Pandemic Preparedness Team in the National Center for Immunization...

  5. LANL spinoff receives NIH grant for respiratory disease diagnostic...

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

    a disposable cartridge, Cai said. In the case of a pandemic, such as SARS or avian influenza, the device also could be made disposable, she added. Mesa Tech's proposed...

  6. A New Approach to a Lyme Disease Vaccine

    SciTech Connect (OSTI)

    Livey, I.; Dunn, J.; O'Rourke, M.; Traweger, A.; Savidis-Dacho, H.; Crowe, B. A.; Barrett, P. N.; Yang, X.; Luft, B. J.

    2011-02-01

    A single recombinant outer surface protein A (OspA) antigen designed to contain protective elements from 2 different OspA serotypes (1 and 2) is able to induce antibody responses that protect mice against infection with either Borrelia burgdorferi sensu stricto (OspA serotype-1) or Borrelia afzelii (OspA serotype-2). Protection against infection with B burgdorferi ss strain ZS7 was demonstrated in a needle-challenge model. Protection against B. afzelii species was shown in a tick-challenge model using feral ticks. In both models, as little as .03 {micro}g of antigen, when administered in a 2-dose immunization schedule with aluminum hydroxide as adjuvant, was sufficient to provide complete protection against the species targeted. This proof of principle study proves that knowledge of protective epitopes can be used for the rational design of effective, genetically modified vaccines requiring fewer OspA antigens and suggests that this approach may facilitate the development of an OspA vaccine for global use.

  7. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, Ronald M. (Berkeley, CA); Blanche, Patricia J. (Berkeley, CA); Orr, Joseph (San Pablo, CA)

    1999-01-01

    A variable rate density gradient electrophoric gel is described which separate LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described.

  8. Update on the Hanford Site Chronic Beryllium Disease Prevention...

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

    in Training Development and CBDPP Revision & Approval Beryllium Work Permit Building AssessmentCharacterizationVerification Sampling Postings Products in Contractor Training...

  9. Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP...

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

    Advocate Domina, Kirk 376-3723 948-9763 Stoner, Mike 373-7587 713-4513 HPMC OMS Holland, Nic 376-1085 (406) 544-4502 Cowley, Dana Phillips MD, Karen 372-0015 376-4716 (509)...

  10. Collaborative Initiative in Biomedical Imaging to Study Complex Diseases

    SciTech Connect (OSTI)

    Lin, Weili; Fiddy, Michael A.

    2012-03-31

    The work reported addressed these topics: Fluorescence imaging; Optical coherence tomography; X-ray interferometer/phase imaging system; Quantitative imaging from scattered fields, Terahertz imaging and spectroscopy; and Multiphoton and Raman microscopy.

  11. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

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

    ... Frequently reported symptoms include one or more of the following: dyspnea (shortness of breath) on exertion, cough, fever, night sweats, and chest pain and, less frequently, ...

  12. Network Science: From the Web to Human Diseases

    SciTech Connect (OSTI)

    Barabasi, Albert-Laszlo

    2008-06-09

    Systems as diverse as the world wide web, Internet or the cell are described by highly interconnected networks with amazingly complex topology. Recent studies indicate that the evolution of these complex networks is governed by simple but generic laws, resulting in apparently universal architectural features. I will discuss this amazing order characterizing our interconnected work, and its implications to how we perceive the impact on communications and medicine, as well as touch upon the next challenge of network research, going beyond the structure and quantifying the dynamics of interconnected systems.

  13. A State-Wide Research Network for Alzheimer's Disease (Technical...

    Office of Scientific and Technical Information (OSTI)

    key services such as (but not limited to) seeking funding research opportunities, financial tracking, regulatory management, central recruitment, training for investigators and ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdClsub 2 (4.5 mgkg) on gestational day 9. As expected, maternal ...

  15. BlueChoice

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

    Surgeon (including maternity services that are not part of OBGyn global delivery fee and complications of pregnancy) 10% after deductible 5 10% after deductible 10% after...

  16. Microsoft Word - PPO Plan Highlight.doc

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

    Surgeon (including maternity services that are not part of OBGyn global delivery fee and complications of pregnancy) 10% after deductible 5 10% after deductible 10% after...

  17. SREL Reprint #3335

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

    however, about the relationship between maternal size and factors affecting offspring fitness, including size, growth and survival. Here, we examined the relationship between...

  18. AtMIN7 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang (Okemos, MI); Nomura, Kinya (East Lansing, MI)

    2011-07-26

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein AtMIN7 mediated protection is enhanced and/or there is a decrease in activity of an AtMIN7 associated virulence protein such as a Pseudomonas syringae pv. tomato DC3000 HopM1. Reagents of the present invention provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  19. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    In 1975 and 1976, 179 smallmouth bass (Micropterus dolomieui) and 85 northern squawfish (Ptychocheilus oregonensis) were collected by angling from the lower Snake and mid-Columbia rivers, southeastern Washington. All fish were examined externally for gas bubble syndrome. Emboli were found beneath membranes of the opercula, body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several smallmouth bass. Presence of gas bubble syndrome corresponded to the spring runoff when total dissolved gas supersaturations in river water exceeded 115%.

  20. Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

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

    Bach, Christian; Sherman, William; Pallis, Jani; Patra, Prabir; Bajwa, Hassan

    2014-01-01

    Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

  1. Method for detecting and diagnosing disease caused by pathological protein aggregation

    DOE Patents [OSTI]

    Stevens, Fred J. (Naperville, IL); Myatt, Elizabeth A. (Riverside, IL); Solomon, Alan (Knoxville, TN)

    2000-01-01

    A method is provided for detecting pathological macromolecules in a patient, comprising obtaining body fluid from the patient, pretreating the body fluid, subjecting the pretreated body fluid to size-exclusion chromatography to create an excluded fluid, and analyzing the excluded fluid to detect macromolecules having a predetermined molecular weight. The method also allows for comparing elution spectra with reference spectra of suspect pathologic proteins.

  2. Chronic disease and early exposure to air-borne mixtures. 2. Exposure assessment

    SciTech Connect (OSTI)

    James Argo

    2007-10-15

    This work is part of a larger study of the impact of early exposure to releases from industry on the etiology of cancer. Releases from all kraft and sulfite mills, coke ovens, oil refineries, copper, nickel, and lead/zinc smelters operating in Canada during the exposure period of 1967-1970 have been determined. All plumes have been expressed in g BaP eq/d using the RASH methodology. The releases have been divided into process, boiler fuel, dioxin, and SO{sub 2} emissions. Combustion sources have been defined with FIREv6.23. Dioxin congenors are expected in all source types when the boiler fuel is heavy fuel oil, wood or wood bark, or coal. All about 90 communities examined have an inverted sex ratio. 53 refs., 2 figs., 4 tabs.

  3. Structure of an aprataxin?DNA complex with insights into AOA1 neurodegenerative disease

    SciTech Connect (OSTI)

    Tumbale, Percy; Appel, C. Denise; Kraehenbuehl, Rolf; Robertson, Patrick D.; Williams, Jessica S.; Krahn, Joe; Ahel, Ivan; Williams, R. Scott (NIEHS); (Manchester)

    2012-09-17

    DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn{sup 2+} complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C{sub 2}HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

  4. Indoor Measurements of Environmental Tobacco Smoke Final Report to the Tobacco Related Disease Research Program

    SciTech Connect (OSTI)

    Apte, Michael G.; Gundel, Lara A.; Dod, Raymond L.; Russell, Marion L.; Singer, Brett C.; Sohn, Michael D.; Sullivan, Douglas P.; Chang, Gee-Minn; Sextro, Richard G.

    2004-03-02

    The objective of this research project was to improve the basis for estimating environmental tobacco smoke (ETS) exposures in a variety of indoor environments. The research utilized experiments conducted in both laboratory and ''real-world'' buildings to (1) study the transport of ETS species from room to room, (2) examine the viability of using various chemical markers as tracers for ETS, and (3) to evaluate to what extent re-emission of ETS components from indoor surfaces might add to the ETS exposure estimates. A three-room environmental chamber was used to examine multi-zone transport and behavior of ETS and its tracers. One room (simulating a smoker's living room) was extensively conditioned with ETS, while a corridor and a second room (simulating a child's bedroom) remained smoking-free. A series of 5 sets of replicate experiments were conducted under different door opening and flow configurations: sealed, leaky, slightly ajar, wide open, and under forced air-flow conditions. When the doors between the rooms were slightly ajar the particles dispersed into the other rooms, eventually reaching the same concentration. The particle size distribution took the same form in each room, although the total numbers of particles in each room depended on the door configurations. The particle number size distribution moved towards somewhat larger particles as the ETS aged. We also successfully modeled the inter-room transport of ETS particles from first principles--using size fractionated particle emission factors, predicted deposition rates, and thermal temperature gradient driven inter-room flows, This validation improved our understanding of bulk inter-room ETS particle transport. Four chemical tracers were examined: ultraviolet-absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and solanesol. Both (UVPM) and (FPM) traced the transport of ETS particles into the non-smoking areas. Nicotine, on the other hand, quickly adsorbed on unconditioned surfaces so that nicotine concentrations in these rooms remained very low, even during smoking episodes. These findings suggest that using nicotine as a tracer of ETS particle concentrations may yield misleading concentration and/or exposure estimates. The results of the solanesol analyses were compromised, apparently by exposure to light during collection (lights in the chambers were always on during the experiments). This may mean that the use of solanesol as a tracer is impractical in ''real-world'' conditions. In the final phase of the project we conducted measurements of ETS particles and tracers in three residences occupied by smokers who had joined a smoking cessation program. As a pilot study, its objective was to improve our understanding of how ETS aerosols are transported in a small number of homes (and thus, whether limiting smoking to certain areas has an effect on ETS exposures in other parts of the building). As with the chamber studies, we examined whether measurements of various chemical tracers, such as nicotine, solanesol, FPM and UVPM, could be used to accurately predict ETS concentrations and potential exposures in ''real-world'' settings, as has been suggested by several authors. The ultimate goal of these efforts, and a future larger multiple house study, is to improve the basis for estimating ETS exposures to the general public. Because we only studied three houses no firm conclusions can be developed from our data. However, the results for the ETS tracers are essentially the same as those for the chamber experiments. The use of nicotine was problematic as a marker for ETS exposure. In the smoking areas of the homes, nicotine appeared to be a suitable indicator; however in the non-smoking regions, nicotine behavior was very inconsistent. The other tracers, UVPM and FPM, provided a better basis for estimating ETS exposures in the ''real world''. The use of solanesol was compromised--as it had been in the chamber experiments.

  5. Update on the Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP)

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

    June 18, 2015 Be Corrective Action Plan (CAP) * Be CAP was approved by DOE-HQ in September 2010 * CAP supplement addressing new consensus process and high-priority Phase 1 products was approved by DOE Office of Environmental Management (DOE-EM) in September 2011 * CAP supplement addressing lower priority Phase 2 and Phase 3 products was approved by DOE-EM on March 13, 2012 Be CAP Status * DOE HQ Enterprise Assessment review March 2015, awaiting final report, no findings, 3 Opportunities for

  6. Surface-enhanced raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, Tuan (Knoxville, TN)

    1999-01-01

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe.

  7. Surface-enhanced Raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, T.

    1999-01-26

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe. 39 figs.

  8. Premier Tools of Energy Research Also Probe Secrets of Viral Disease

    DOE R&D Accomplishments [OSTI]

    Chui, Glennda

    2011-03-28

    Advanced light sources peer into matter at the atomic and molecular scales, with applications ranging from physics, chemistry, materials science, and advanced energy research, to biology and medicine.

  9. Method of treating inflammatory diseases using a radiolabeled ferric hydroxide calloid

    DOE Patents [OSTI]

    Atcher, Robert W.; Hines, John J.

    1992-01-01

    A ferric hydroxide colloid having an alpha-emitting radionuclide essentially on the outer surfaces and a method of forming same. The method includes oxidizing a ferrous hydroxide to ferric hydroxide in the presence of a preselected radionuclide to form a colloid having the radionuclide on the outer surface thereof, and thereafter washing the colloid, and suspending the washed colloid in a suitable solution. The labelled colloid is useful in cancer therapy and for the treatment of inflamed joints.

  10. Compositions for chromosome-specific staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    1998-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  11. Compositions for chromosome-specific staining

    DOE Patents [OSTI]

    Gray, J.W.; Pinkel, D.

    1998-05-26

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. The methods produce staining patterns that can be tailored for specific cytogenetic analyses. The probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. The invention provides for automated means to detect and analyze chromosomal abnormalities. 17 figs.

  12. Methods And Compositions For Chromosome-Specific Staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    2003-08-19

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  13. Methods of biological dosimetry employing chromosome-specific staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    2000-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  14. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    SciTech Connect (OSTI)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-12-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  15. SU-E-T-309: Tangential Modulated Arc Therapy: A Novel Technique for the Treatment of Superficial Disease

    SciTech Connect (OSTI)

    Hadsell, M; Chin, E; Li, R; Xing, L; Bush, K

    2014-06-01

    Purpose: We propose a new type of treatment that employs a modulated and sliding tangential photon field to provide superior coverage of superficial targets when compared to other commonly employed methods while drastically reducing dose to the underlying sensitive structures often present in these cases. Methods: Modulated treatment plans were formulated for a set of three representative cases. The first was a revised treatment of a scalp sarcoma, while the second was a treatment of a right posterior chest wall sarcoma. For these cases, asymmetric jaw placement, angular limitations, and central isocenter placements were used to force the optimization algorithm into finding solutions with beamlines that were not perpendicular to the body surface. The final case targeted the chest wall of a breast cancer patient, in which standard treatments were compared to the use of modulated fields with multiple isocenters along the chest wall. Results: When compared with unrestricted modulated arcs, the tangential arc scalp treatment reduced the max and mean doses delivered to the brain by 33Gy (from 55 to 22Gy) and 6Gy (from 14Gy to 8Gy), respectively. In the right posterior chest wall case, the V10 in the ipsilateral lung was kept below 5% while retaining a Rx dose (45Gy) target coverage of over 97%. For the breast case, the modulated plan achieved reductions in high dose to the ipsilateral lung and heart by a factor of 2–3 when compared to classic laterally opposed tangents and reduced the V5 by 40% when compared to standard modulated arcs. Conclusion: Tangential modulated arc therapy has outperformed the conventional modalities of treatment for superficial lesions used in our clinic. We hope that with the advent of digitally controlled linear accelerators, we can uncover further benefits of this new technique and extend its applicability to a wider section of the patient population.

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary ...

  17. Organ-on-a-chip | The Ames Laboratory

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

    a "placenta-on-a-chip" in order to mimic the nutrientwaste transfer between maternal blood and fetal blood that occurs in the cotyledon section of the placenta, and to test and...

  18. Thermal Imaging of Medical Saw Blades and Guides (Conference) | SciTech

    Office of Scientific and Technical Information (OSTI)

    Connect Conference: Thermal Imaging of Medical Saw Blades and Guides Citation Details In-Document Search Title: Thermal Imaging of Medical Saw Blades and Guides Better Than New, LLC., has developed a surface treatment to reduce the friction and wear of orthopedic saw blades and guides. The medical saw blades were thermally imaged while sawing through fresh animal bone and an IR camera was used to measure the blade temperature as it exited the bone. The thermal performance of as-manufactured

  19. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect (OSTI)

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXR?), we measured LXR? expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXR? protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXR? activity. • Moreover, this involves nicotine-induced enhanced acetylation of histone H3 [K9,14]. • This provides a mechanism for developmental origins of health and disease (DOHaD)

  20. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    SciTech Connect (OSTI)

    Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min; Yeh, Kun-Tu; Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu; Hsiao, Shu-Huei

    2014-10-24

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPAR? were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

  1. Picture of the Week: Hot cells for medical isotopes

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

    the diagnosis of cardiac disease, calibration of PET scanners which in turn diagnose cancer, neurological disease, inflammatory diseases, trauma, and other circulatory diseases,...

  2. Converting Energy to Medical Progress

    Office of Scientific and Technical Information (OSTI)

    heart disease, lymphoma, leukemia, diabetes, Alzheimer's and Parkinson's diseases, ... disease, cystic fibrosis, Huntington's disease, sickle-cell anemia, diabetes, and cancer. ...

  3. Developing microbe-plant interactions for applications in plant-growth promotion and disease control, production of useful compounds, remediation, and carbon sequestration

    SciTech Connect (OSTI)

    Wu, C.H.; Bernard, S.; Andersen, G.L.; Chen, W.

    2009-03-01

    Interactions between plants and microbes are an integral part of our terrestrial ecosystem. Microbe-plant interactions are being applied in many areas. In this review, we present recent reports of applications in the areas of plant-growth promotion, biocontrol, bioactive compound and biomaterial production, remediation and carbon sequestration. Challenges, limitations and future outlook for each field are discussed.

  4. Changes in Gas Bubble Disease Signs and Survival of Migrating Juvenile Salmonids Experimentally Exposed to Supersaturated Gasses, 1995-1996 Progress Report.

    SciTech Connect (OSTI)

    Absolon, Randall F.

    1997-11-01

    Research conducted in 1996 to evaluate (1) changes in GBD signs in juvenile salmonids resulting from passage through turbine intakes and bypass systems, and (2) relative survival during migration through the lower Snake River for juvenile salmonids experimentally exposed to supersaturation of dissolved gas.

  5. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    SciTech Connect (OSTI)

    Little, Mark P.; Stovall, Marilyn; Smith, Susan A.; Kleinerman, Ruth A.

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  6. Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion

    SciTech Connect (OSTI)

    Chacon, J.N.; Chedekel, M.R.; Land, E.J.; Truscott, T.G.

    1987-04-29

    Various unstable intermediate oxidation states have been postulated in the metabolic activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl pyridinium ion. We now report the first direct observation of these free radical intermediates by pulse radiolysis and flash photolysis. Studies are described of various reactions of such species, in particular with dopamine whose autoxidation to dopamine quinone is reported to be potentiated by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine.

  7. Method and product for phosphosilicate slurry for use in dentistry and related bone cements

    DOE Patents [OSTI]

    Wagh, Arun S.; Primus, Carolyn

    2006-08-01

    The present invention is directed to magnesium phosphate ceramics and their methods of manufacture. The composition of the invention is produced by combining a mixture of a substantially dry powder component with a liquid component. The substantially dry powder component comprises a sparsely soluble oxide powder, an alkali metal phosphate powder, a sparsely soluble silicate powder, with the balance of the substantially dry powder component comprising at least one powder selected from the group consisting of bioactive powders, biocompatible powders, fluorescent powders, fluoride releasing powders, and radiopaque powders. The liquid component comprises a pH modifying agent, a monovalent alkali metal phosphate in aqueous solution, the balance of the liquid component being water. The use of calcined magnesium oxide as the oxide powder and hydroxylapatite as the bioactive powder produces a self-setting ceramic that is particularly suited for use in dental and orthopedic applications.

  8. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    SciTech Connect (OSTI)

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in animals and humans needs to be defined.

  9. DOE Science Showcase - Protein Folding | OSTI, US Dept of Energy...

    Office of Scientific and Technical Information (OSTI)

    are believed to cause some neurodegenerative diseases such as alzheimer's disease, cystic fibrosis, amyotrophic lateral sclerosis, huntington's and parkinson's diseases and cancer. ...

  10. Energy Systems and Population Health

    SciTech Connect (OSTI)

    Ezzati, Majid; Bailis, Rob; Kammen, Daniel M.; Holloway, Tracey; Price, Lynn; Cifuentes, Luis A.; Barnes, Brendon; Chaurey, Akanksha; Dhanapala, Kiran N.

    2004-04-12

    It is well-documented that energy and energy systems have a central role in social and economic development and human welfare at all scales, from household and community to regional and national (41). Among its various welfare effects, energy is closely linked with people s health. Some of the effects of energy on health and welfare are direct. With abundant energy, more food or more frequent meals can be prepared; food can be refrigerated, increasing the types of food items that are consumed and reducing food contamination; water pumps can provide more water and eliminate the need for water storage leading to contamination or increased exposure to disease vectors such as mosquitoes or snails; water can be disinfected by boiling or using other technologies such as radiation. Other effects of energy on public health are mediated through more proximal determinants of health and disease. Abundant energy can lead to increased irrigation, agricultural productivity, and access to food and nutrition; access to energy can also increase small-scale income generation such as processing of agricultural commodities (e.g., producing refined oil from oil seeds, roasting coffee, drying and preserving fruits and meats) and production of crafts; ability to control lighting and heating allows education or economic activities to be shielded from daily or seasonal environmental constraints such as light, temperature, rainfall, or wind; time and other economic resources spent on collecting and/or transporting fuels can be used for other household needs if access to energy is facilitated; energy availability for transportation increases access to health and education facilities and allow increased economic activity by facilitating the transportation of goods and services to and from markets; energy for telecommunication technology (radio, television, telephone, or internet) provides increased access to information useful for health, education, or economic purposes; provision of energy to rural and urban health facilities allows increased delivery and coverage of 3 various health services and interventions such as tests and treatments, better storage of medicine and vaccines, disinfection of medical equipment by boiling or radiation, and more frequent and efficient health system encounters through mobile clinics or longer working hours; and so on. In fact, while the dominant view of development-energy-health linkages has been that improvements in energy and health are outcomes of the socioeconomic development process (e.g., the ''energy ladder'' framework discussed below), it has even been argued that access to higher quality energy sources and technologies can initiate a chain of demographic, health, and development outcomes by changing the household structure and socioeconomic relationships. For example, in addition to increased opportunities for food and income production, reduced infant mortality as a result of transition to cleaner fuels or increased coverage of vaccination with availability of refrigerators in rural clinics may initiate a process of ''demographic transition'' to low-mortality and low-fertility populations (14). Such a transition has historically been followed with further improvements in maternal and child health and increased female participation in the labor markets and other economic activities.

  11. SSRL HEADLINES Nov 2006

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

    Contents of this Issue: Science Highlight - Untangling Brain Disease Science Highlight - ... 1. Science Highlight - Untangling Brain Disease (contacts: X. Wang, ...

  12. SREL Reprint #3208

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

    8 Interactive effects of maternal and environmental exposure to coal combusion wastes decrease survival of larval southern toads (Bufo terrestris) Brian S. Metts1, Kurt A. Buhlmann1, David E. Scott1, Tracey D. Tuberville1, and William A. Hopkins2 1Savannah River Ecology Laboratory, Drawer E, Aiken, SC 29802, USA 2Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, VA 24061, USA Abstract: We conducted a mesocosm study to assess the individual and interactive effects of

  13. SREL Reprint #3245

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

    5 Maternal transfer of contaminants and reduced reproductive success of southern toads (Bufo [Anaxyrus] terrestris) exposed to coal combustion waste Brian S. Metts1, Kurt A. Buhlmann1, Tracey D. Tuberville1, David E. Scott1, and William A. Hopkins2 1Savannah River Ecology Laboratory, University of Georgia, Drawer E, Aiken, South Carolina 29802, USA 2Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, Virginia 24061, USA Abstract: Bioaccumulation of contaminants and

  14. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    SciTech Connect (OSTI)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  15. ATOMIC LAYER DEPOSITION OF TITANIUM OXIDE THIN FILMS ONNANOPOROUS ALUMINA TEMPLATES FOR MEDICAL APPLICATIONS

    SciTech Connect (OSTI)

    Brigmon, R.

    2009-05-05

    Nanostructured materials may play a significant role in controlled release of pharmacologic agents for treatment of cancer. Many nanoporous polymer materials are inadequate for use in drug delivery. Nanoporous alumina provides several advantages over other materials for use in controlled drug delivery and other medical applications. Atomic layer deposition was used to coat all the surfaces of the nanoporous alumina membrane in order to reduce the pore size in a controlled manner. Both the 20 nm and 100 nm titanium oxide-coated nanoporous alumina membranes did not exhibit statistically lower viability compared to the uncoated nanoporous alumina membrane control materials. In addition, 20 nm pore size titanium oxide-coated nanoporous alumina membranes exposed to ultraviolet light demonstrated activity against Escherichia coli and Staphylococcus aureus bacteria. Nanostructured materials prepared using atomic layer deposition may be useful for delivering a pharmacologic agent at a precise rate to a specific location in the body. These materials may serve as the basis for 'smart' drug delivery devices, orthopedic implants, or self-sterilizing medical devices.

  16. ORISE: Recent Graduate Research Experiences - Lindsay Gabbert

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

    Control and Prevention concentrated on human disease. "Previously, I was focused on dengue hemorrhagic fever-a potentially life-threatening mosquito-borne tropical disease which...

  17. Genome Engineering with TAL Effector Nucleases

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

    sequences in patients suffering from genetic diseases, the modification or insertion of genes in plants, and the generation of unique cell lines for treatment of diseases such as...

  18. Sandia National Laboratories: Research: Biodefense

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

    Biodefense Creating novel tools for detecting and fighting disease Raptor Infectious diseases and bioterrorism events may seem like very different phenomena-but both share enormous...

  19. Tracking Living Cells as They Differentiate in Real Time

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

    Alzheimer's disease, macular degeneration of the retina in diabetes, and mitochondrial diseases in children. In addition, specific processes like protein glycation can also be...

  20. ORISE: ORAU-managed beryllium lab marks outstanding year in 2013

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

    higher risk of developing Chronic Beryllium Disease, a chronic disease that scars the lungs making it more difficult for oxygen to transfer into the bloodstream. The test...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain ... Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F ...

  2. 1

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

    and crisis managers determine in real time whether an emerging infectious disease ... The ability to look at small disease populations in real time could allow responders and ...

  3. One Vaccine Leads to Another

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

    particular-have led to vaccines against other diseases, like the flu and bacterial meningitis. Often, nontoxic forms of various disease toxins are used to make vaccines,...

  4. Former Workers Medical Facilities with Experience Evaluating...

    Energy Savers [EERE]

    Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease April...

  5. A Basic Overview of the Former Worker Medical Screening Program...

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

    ... occupationally related disease are referred to the DOL for ... Chronic respiratory diseases; Hearing loss; Liver and kidney problems; and Some forms of cancer. FWP offers former ...

  6. BeryllFactShts12-7-01

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

    ... WHAT ARE THE SYMPTOMS OF CHRONIC BERYLLIUM DISEASE? * Symptoms of Chronic Beryllium Disease include: - Shortness of Breath, especially with activity - Cough - Chest Pain - Fatigue ...

  7. Guide to Minimizing Compress-based Cooling

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

    Cover photo: Center for Disease Control and Prevention's Arlen Specter ... Photo from Center for Disease Control, NRELPIX 16419 3 Acknowledgements The author would ...

  8. Enterprise Assessments Follow-up Review of the Hanford Site Chronic...

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

    Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 Enterprise Assessments Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention...

  9. Audit Report: IG-0726 | Department of Energy

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

    of beryllium disease, two of the objectives of the Chronic Beryllium Disease Prevention Program (Prevention Program). PDF icon Audit Report: IG-0726 More Documents &...

  10. ORISE Health Communication and Training: Capabilities

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

    the public to better understand health challenges, such as cancer, heart disease and diabetes, as well as new infectious disease threats. The Oak Ridge Institute for Science and...

  11. Tracking Living Cells as They Differentiate in Real Time

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

    these projects will target Alzheimer's disease, macular degeneration of the retina in diabetes, and mitochondrial diseases in children. In addition, specific processes like protein...

  12. New insights into regulating the gut's microbial community |...

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

    of microbiota-associated pathologies such as inflammatory bowel disease, obesity, diabetes, and celiac disease. Study: "Innate and Adaptive Humoral Responses Coat Distinct...

  13. ORISE: Training and Tools

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

    Training and Tools Chronic diseases such as diabetes, heart disease and cancer afflict more people every year and have resulted in increased demand for trained health care...

  14. Human Genome Research: Decoding DNA

    Office of Scientific and Technical Information (OSTI)

    defects may lead to genetically linked diseases such as certain forms of kidney disease, prostate and colorectal cancer, leukemia, hypertension, diabetes, and atherosclerosis. ... ...

  15. Understanding Radioactive Waste Raymond L. Murray, Professor...

    Office of Scientific and Technical Information (OSTI)

    ... Cancer Stroke Accidents, total Motor vehicle 52,411 Others 53,150 Influenza pneumonia Diabetes Liver disease Hardening of arteries Suicide Infant mortality Lung disease Homicide ...

  16. Workplace Charging Challenge Partner: Baxter International Inc...

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

    ... Baxter International Inc., through its subsidiaries, develops, manufactures and markets ... diseases, kidney disease, trauma, and other chronic and acute medical conditions. ...

  17. SSRL HEADLINES May 2009

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

    Science Highlight - Visualizing Brain Metals in Health and Disease Science ... 2. Science Highlight - Visualizing Brain Metals in Health and Disease (contact: H. ...

  18. OSTI, US Dept of Energy, Office of Scientific and Technical Informatio...

    Office of Scientific and Technical Information (OSTI)

    effort, the Alzheimer's Disease Neuroimaging Initiative, was formed to find the biological markers that show the progression of Alzheimer's disease in the human brain. ...

  19. Reducing Infant Mortality Rate With Ultrasound in Rural India | GE Global

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

    Research Reducing Infant Mortality Rate With Ultrasound in Rural India 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) Reducing Infant Mortality Rate With Ultrasound in Rural India Kajoli Krishnan 2011.07.28 The United Nations is committed to reducing global infant mortality rate (IMR) and maternal mortality ratio

  20. EA-0896: Finding of No Significant Impact

    Broader source: Energy.gov [DOE]

    Center for Nuclear Medicine Research in Alzheimer's Disease Health Sciences Center- West Virginia University

  1. EA-0896: Final Environmental Assessment

    Broader source: Energy.gov [DOE]

    Center for Nuclear Medicine Research in Alzheimer's Disease Health Sciences Center- West Virginia University

  2. U.S. Department of Energy Illness and Injury Surveillance Program...

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

    their absence rates for diseases such as diabetes and hypertension are increasing as well. ......... 34 Diabetes ......

  3. November 6, 2008; HSS/Union Working Group Meeting on Aging Workforce...

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

    their absence rates for diseases such as diabetes and hypertension are increasing as well. ......... 34 Diabetes......

  4. Microstructural characterization of as-cast biocompatible Co-Cr-Mo alloys

    SciTech Connect (OSTI)

    Giacchi, J.V.; Morando, C.N.; Fornaro, O.; Palacio, H.A.

    2011-01-15

    The microstructure of a cobalt-base alloy (Co-Cr-Mo) obtained by the investment casting process was studied. This alloy complies with the ASTM F75 standard and is widely used in the manufacturing of orthopedic implants because of its high strength, good corrosion resistance and excellent biocompatibility properties. This work focuses on the resulting microstructures arising from samples poured under industrial environment conditions, of three different Co-Cr-Mo alloys. For this purpose, we used: 1) an alloy built up from commercial purity constituents, 2) a remelted alloy and 3) a certified alloy for comparison. The characterization of the samples was achieved by using optical microscopy (OM) with a colorant etchant to identify the present phases and scanning electron microscopy (SE-SEM) and energy dispersion spectrometry (EDS) techniques for a better identification. In general the as-cast microstructure is a Co-fcc dendritic matrix with the presence of a secondary phase, such as the M{sub 23}C{sub 6} carbides precipitated at grain boundaries and interdendritic zones. These precipitates are the main strengthening mechanism in this type of alloys. Other minority phases were also reported and their presence could be linked to the cooling rate and the manufacturing process variables and environment. - Research Highlights: {yields}The solidification microstructure of an ASTM-F75 type alloy were studied. {yields}The alloys were poured under an industrial environment. {yields}Carbides and sigma phase identified by color metallography and scanning microscopy (SEM and EDS). {yields}Two carbide morphologies were detected 'blocky type' and 'pearlite type'. {yields}Minority phases were also detected.

  5. ORISE: Recent Graduate Research Experiences - Lindsay Gabbert

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

    Lindsay Gabbert Animal disease research opportunity proves to be rewarding assignment for graduate student Lindsay Gabbert Lindsay Gabbert performs research at the Plum Island Animal Disease Center, where she is helping to improve the vaccination for foot-and-mouth disease. Prior to Plum Island, she completed a fellowship at the Centers for Disease Control and Prevention, where she concentrated on human diseases. For Lindsay Gabbert, her current position as a research participant is a different

  6. Genomics-enabled sensor platform for rapid detection of viruses related to

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

    disease outbreak. (Technical Report) | SciTech Connect Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Citation Details In-Document Search Title: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the

  7. Genomics-enabled sensor platform for rapid detection of viruses related to

    Office of Scientific and Technical Information (OSTI)

    disease outbreak. (Technical Report) | SciTech Connect SciTech Connect Search Results Technical Report: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Citation Details In-Document Search Title: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack

  8. US Department of Energy - Office of FreedomCar and Vehicle Technologies and US Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health Inter-Agency Agreement Research on "The Analysis of Genotoxic Activities of Exhaust Emissions from Mobile Natural Gas, Diesel, and Spark-Ignition Engines"

    SciTech Connect (OSTI)

    William E. Wallace

    2006-09-30

    The US Department of Energy-Office of Heavy Vehicle Technologies (now the DOE-Office of FreedomCar and Vehicle Technologies) signed an Interagency Agreement (IAA) with National Institute for Occupational Safety and Health (NIOSH), No.01-15 DOE, 9/4/01, for 'The analysis of genotoxic activities of exhaust emissions from mobile natural gas, diesel, and spark-ignition engines'; subsequently modified on 3/27/02 (DOE IAG No.01-15-02M1); subsequently modified 9/02/03 (IAA Mod No. 01-15-03M1), as 'The analysis of genotoxic activities of exhaust emissions from mobile internal combustion engines: identification of engine design and operational parameters controlling exhaust genotoxicity'. The DOE Award/Contract number was DE-AI26-01CH11089. The IAA ended 9/30/06. This is the final summary technical report of National Institute for Occupational Safety and Health research performed with the US Department of Energy-Office of FreedomCar and Vehicle Technologies under that IAA: (A) NIOSH participation was requested by the DOE to provide in vitro genotoxicity assays of the organic solvent extracts of exhaust emissions from a suite of in-use diesel or spark-ignition vehicles; (B) research also was directed to develop and apply genotoxicity assays to the particulate phase of diesel exhaust, exploiting the NIOSH finding of genotoxicity expression by diesel exhaust particulate matter dispersed into the primary components of the surfactant coating the surface of the deep lung; (C) from the surfactant-dispersed DPM genotoxicity findings, the need for direct collection of DPM aerosols into surfactant for bioassay was recognized, and design and developmental testing of such samplers was initiated.

  9. Final report on the developmental toxicity of ethylenediamine (CAS No. 107-15-3) in New Zealand white rabbits. Report for November-February 1992

    SciTech Connect (OSTI)

    Not Available

    1993-03-01

    Ethylenediamine (EDA) is a major industrial chemical with an estimated U.S. production of 64 million pounds in 1985. EDA is used as a chemical intermediate or solvent in manufacturing, as a paint thinner, and as a constituent of certain cosmetic, pharmaceutical and veterinary products. Based upon its widespread applications and the potential for exposure in pregnant women, EDA was evaluated for maternal and developmental toxicity using a laboratory animal model. Artificially-inseminated New Zealand White rabbits (26/group) were administered ethylenediamine (0, 10, 40 or 80 mg/kg/day) by gavage on gestational days (gd) 6 through 19. The doses administered were equivalent to 0, 22, 89 or 178 of EDA.2HC1. Maternal clinical signs, body weight, and food consumption were monitored at regular intervals throughout gestation. At termination (gd 30), the uterus was removed and examined to determine pregnancy status and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses examined for external, visceral and skeletal defects.

  10. The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt

    SciTech Connect (OSTI)

    Clements, Craig S.; Kjer-Nielsen, Lars; Kostenko, Lyudmila; McCluskey, James; Rossjohn, Jamie

    2006-01-01

    X-ray diffraction data were collected to 1.9 Ĺ from crystals of HLA-G. Cobalt ions were found to be essential for the production of diffracting crystals. HLA-G is a nonclassical class I major histocompatibility complex (MHC) molecule that is primarily expressed at the foetal–maternal interface. Although the role of HLA-G has not been fully elucidated, current evidence suggests it protects the foetus from the maternal immune response. In this report, HLA-G (44 kDa) is characterized by expression in Escherichia coli. The inclusion bodies were refolded in complex with a peptide derived from histone H2A (RIIPRHLQL), purified and subsequently crystallized. Correct refolding was determined using two conformation-dependent antibodies. Cobalt ions were shown to be an essential ingredient for obtaining diffraction-quality crystals. The crystals, which diffracted to 1.9 Ĺ resolution, belonged to space group P3{sub 2}2{sub 1}, with unit-cell parameters a = b = 77.15, c = 151.72 Ĺ.

  11. Selenium Preferentially Accumulates in the Eye Lens Following Embryonic Exposure: A Confocal X-ray Fluorescence Imaging Study

    SciTech Connect (OSTI)

    Choudhury, Sanjukta; Thomas, Jith; Sylvain, Nicole J.; Ponomarenko, Olena; Gordon, Robert A.; Heald, Steve M.; Janz, David M.; Krone, Patrick H.; Coulthard, Ian; George, Graham N.; Pickering, Ingrid J.

    2015-02-17

    Maternal transfer of elevated selenium (Se) to offspring is an important route of Se exposure for fish in the natural environment. However, there is a lack of information on the tissue specific spatial distribution and speciation of Se in the early developmental stages of fish, which provide important information about Se toxicokinetics. The effect of maternal transfer of Se was studied by feeding adult zebrafish a Se-elevated or a control diet followed by collection of larvae from both groups. Novel confocal synchrotron-based techniques were used to investigate Se within intact preserved larvae. Confocal X-ray fluorescence imaging was used to compare Se distributions within specific planes of an intact larva from each of the two groups. The elevated Se treatment showed substantially higher Se levels than the control; Se preferentially accumulated to highest levels in the eye lens, with lower levels in the retina, yolk and other tissues. Confocal X-ray absorption spectroscopy was used to determine that the speciation of Se within the eye lens of the intact larva was a selenomethionine-like species. Preferential accumulation of Se in the eye lens may suggest a direct cause-and-effect relationship between exposure to elevated Se and Se-induced ocular impairments reported previously. This study illustrates the effectiveness of confocal X-ray fluorescence methods for investigating trace element distribution and speciation in intact biological specimens

  12. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  13. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.

    1994-02-01

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  14. Glomerular-specific imprinting of the mouse Gs{alpha} gene: How does this relate to hormone resistance in Albright hereditary osteodystrophy?

    SciTech Connect (OSTI)

    Williamson, C.M.; Dutton, E.R.; Seymour, A.

    1996-09-01

    The gene for alpha-stimulating guanine-nucleotide binding polypeptide, Gnas, has been considered as a candidate for the imprinting effects ascribed to distal mouse Chromosome (Chr) 2. Its human homologue (GNAS1) appears, from clinical and biochemical studies of patients with Albright hereditary ostodystrophy, to be paternally imprinted. GNAS1 maps to 20q13, a region that shows linkage conservation with distal mouse Chr 2. We have mapped Gnas within the imprinting region on distal Chr 2 by linkage analysis. To establish if Gnas is imprinted, we have looked for expression differences in tissues taken from mice carrying maternal duplication/paternal deficiency for distal Chr 2 (MatDp2) and its reciprocal (PatDp2). RNA in situ hybridization revealed high levels of Gnas mRNA in glomeruli of PatDp2 embryos at late gestation and lower levels in glomeruli of MatDp2 embryos. These results strongly suggest that Gnas is maternally imprinted and suggest that the mouse gene may be imprinted in a manner opposite the predicted in human. 42 refs., 4 figs.

  15. Three Los Alamos scientists named 'Most Influential Scientific...

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

    disease only comes when the work has an impact on treating diseases such as HIV, influenza and hepatitis and ultimately in saving lives." Perelson is part of a multinational...

  16. 'Most Influential Scientific Minds'

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

    disease only comes when the work has an impact on treating diseases such as HIV, influenza and hepatitis and ultimately in saving lives." Perelson is part of a multinational...

  17. First LEU-Produced Molybdenum-99 Approved for Patient Use Arrives...

    National Nuclear Security Administration (NNSA)

    Mo-99's primary uses include the detection of disease, including heart disease and cancer, and to study organ structure and function. The isotope's short half-life and...

  18. R&D Magazine's 2010 Scientist of the Year | Department of Energy

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

    of Parkinson's Disease, and may also show the way to a quicker and faster diagnosis of liver disease and some forms of cancer. In addition to his work on problem proteins, Dr. ...

  19. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    ACIDS; CALIFORNIA; CHAINS; CHEMISTRY; DISEASES; FIBROSIS; FORECASTING; GENETICS; OPTIMIZATION; PROTEIN STRUCTURE; PROTEINS; QUEUES; SHAPE; SIMULATION PROTEIN STRUCTURE...

  20. Manipulating and Visualizing Proteins Simon, Horst D. 59 BASIC...

    Office of Scientific and Technical Information (OSTI)

    ACIDS; CALIFORNIA; CHAINS; CHEMISTRY; DISEASES; FIBROSIS; FORECASTING; GENETICS; OPTIMIZATION; PROTEIN STRUCTURE; PROTEINS; QUEUES; SHAPE; SIMULATION PROTEIN STRUCTURE...

  1. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    AMINO ACIDS CALIFORNIA CHAINS CHEMISTRY DISEASES FIBROSIS FORECASTING GENETICS OPTIMIZATION PROTEIN STRUCTURE PROTEINS QUEUES SHAPE SIMULATION PROTEIN STRUCTURE PREDICTION...

  2. ORISE: Recent Graduate Research Experiences - Camila Dias Colberg

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

    Camila Dias Colberg Animal disease research opportunity proves to be rewarding assignment for graduate student Camila Dias Colberg Camila Dias Colberg is supporting research at the Plum Island Animal Disease Center to find a more effective treatment for foot-and-mouth disease. A Brazilian veterinarian, she hopes one day to be a licensed veterinarian in the United States. Click image to enlarge. The impact of foot-and-mouth disease hit home for Camila Dias Colberg in 2005 while working on her

  3. Multi-analyte analysis of saliva biomarkers as predictors of periodontal

    Office of Scientific and Technical Information (OSTI)

    and pre-implant disease (Patent) | SciTech Connect Multi-analyte analysis of saliva biomarkers as predictors of periodontal and pre-implant disease Citation Details In-Document Search Title: Multi-analyte analysis of saliva biomarkers as predictors of periodontal and pre-implant disease The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal and/or peri-implant disease. More specifically, the invention provides a panel of biomarkers

  4. SSRL HEADLINES October 2008

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

    Contents of this Issue: Science Highlight - Role of Specific Protein Mutations in Causing Human Disease Revealed SSRL Exchanges...

  5. antagonist Haga, Kazuko; Kruse, Andrew C.; Asada, Hidetsugu;

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY; CENTRAL NERVOUS SYSTEM; DISEASES; DISSOCIATION; NERVES; ORGANS; POTASSIUM; PROTEINS; REGULATIONS; RESIDUES; TARGETS; TYROSINE The parasympathetic branch of the autonomic...

  6. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY CENTRAL NERVOUS SYSTEM DISEASES DISSOCIATION NERVES ORGANS POTASSIUM PROTEINS REGULATIONS RESIDUES TARGETS TYROSINE The parasympathetic branch of the autonomic...

  7. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY; CENTRAL NERVOUS SYSTEM; DISEASES; DISSOCIATION; NERVES; ORGANS; POTASSIUM; PROTEINS; REGULATIONS; RESIDUES; TARGETS; TYROSINE",,"The parasympathetic branch of the...

  8. 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; ...

  9. ORISE: ORISE to develop needs assessment plan to support CDC infectious

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

    disease initiative to develop needs assessment plan to support CDC infectious disease initiative ORISE team will identify training and educational needs among laboratory professionals, bioinformatics professionals and epidemiologists How ORISE is Making a Difference The Oak Ridge Institute for Science and Education (ORISE) will design and carry out a needs assessment plan for the Center for Disease Control and Prevention's (CDC) Advanced Molecular Detection and Response to Infectious Disease

  10. Alina Deshpande-Strengthening the fight against pandemics

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

    Strengthening the fight against pandemics Alina Deshpande-Strengthening the fight against pandemics She is dedicated to strengthening the world's fight against infectious diseases by providing new tools for early detection and mitigation of disease outbreaks. March 10, 2014 Alina Deshpande She is dedicated to strengthening the world's fight against infectious diseases by providing new tools for early detection and mitigation of disease outbreaks. Deshphande's advice? "You can be successful

  11. CRAD, Assessment of the Site- February 17, 2010

    Broader source: Energy.gov [DOE]

    Assessment of the Site Chronic Beryllium Disease Prevention Plan (CBDPP) Implementation (HSS CRAD 64-37, Rev 0)

  12. Independent Activity Report, Lawrence Livermore National Laboratory...

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

    Independent Activity Report, Lawrence Livermore National Laboratory - March 2011 March 2011 Lawrence Livermore National Laboratory Chronic Beryllium Disease Prevention Program ...

  13. Introduction to Brookhaven National Laboratory

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

    and academic users * Researching battery storage, Alzheimer's disease, breast cancer, HIVAIDS, environmental cleanup technology, and more National Synchrotron Light ...

  14. Crystal structure of N-{N-[N-acetyl-(S)-leucyl]-(S)-leucyl}norleucinal...

    Office of Scientific and Technical Information (OSTI)

    Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, ... implicated in several neurodegenerative diseases and other disorders, including cancer. ...

  15. Brookhaven National Laboratory: A Brief Overview

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

    and academic users Researching battery storage, Alzheimer's disease, breast cancer, HIVAIDS, environmental cleanup technology, and more National Synchrotron Light ...

  16. ORISE: Consumer Health Resource Information Service (CHRIS) ...

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

    that disproportionately affect minorities, including: HIVAIDS Cardiovascular disease Diabetes Immunization Cancer Infant mortality ORISE provides health information training for...

  17. Genes from the 20Q13 amplicon and their uses

    DOE Patents [OSTI]

    Gray, Joe (San Francisco, CA); Collins, Colin (San Rafael, CA); Hwang, Soo-in (Berkeley, CA); Godfrey, Tony (San Francisco, CA); Kowbel, David (Oakland, CA); Rommens, Johanna (Toronto, CA)

    1999-01-01

    The present invention relates to cDNA sequences from a region of amplification on chromosome 20 associated with disease. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases. The sequences can also be used for treatment of diseases.

  18. Laminated root rot in western North America. Forest Service general technical report

    SciTech Connect (OSTI)

    Thies, W.G.; Sturrock, R.N.

    1995-04-01

    Laminated root rot, caused by Phellinus weirii (Murr.) Gib., is a serious root disease affecting Douglas-fir and other commercially important species of conifers in northwestern North America. This report gives an overview of the disease as it occurs in the Pacific Northwest in Canada and the United States. Information on recognizing crown symptoms and signs of the disease is presented. The disease cycle of laminated root rot, from initiation to intensification and distribution within infected stands, is described. Finally, disease management strategies during stand development and at stand regeneration are discussed. Features on mechanical approaches also are included. The report is intended as a general reference for a wide audience.

  19. Placental concentrations of heavy metals in a mother-child cohort

    SciTech Connect (OSTI)

    Amaya, E.; Gil, F.; Freire, C.; National School of Public Health, Oswaldo Cruz Foundation , 21041-210 Rio de Janeiro ; Olmedo, P.; Fernandez-Rodriguez, M.; Fernandez, M.F.; Olea, N.; CIBER de Epidemiologia y Salud Publica

    2013-01-15

    Heavy metals are environmental contaminants with properties known to be toxic for wildlife and humans. Despite strong concerns about their harmful effects, little information is available on intrauterine exposure in humans. The aim of this study was to evaluate prenatal exposure to As, Cd, Cr, Hg, Mn, and Pb and its association with maternal factors in a population-based mother-child cohort in Southern Spain. Between 2000 and 2002, 700 pregnant women were recruited and 137 placentas from the cohort were randomly selected and analyzed for the selected metals by atomic absorption. Maternal sociodemographic and lifestyle factors were obtained by questionnaire after delivery. Bivariate analysis and multivariate linear regression were performed. Cd and Mn concentrations were detected in all placentas, while Cr, Pb, and Hg were found in 98.5%, 35.0%, and 30.7% of samples, respectively. The highest concentrations were observed for Pb (mean: 94.80 ng/g wet weight of placenta), followed by Mn (63.80 ng/g), Cr (63.70 ng/g), Cd (3.45 ng/g), and Hg (0.024 ng/g). Arsenic was not detected in any sample. Gestational age and smoking during pregnancy were associated with placental Cd concentrations, while no factor appeared to influence concentrations of Cr, Hg, Mn, or Pb. In comparison to results of European studies, these concentrations are in a low-intermediate position. Studies are required to investigate the factors contributing to early exposure to heavy metals and to determine how placental transfer of these toxic compounds may affect children's health.

  20. Repeated in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure affects male gonads in offspring, leading to sex ratio changes in F{sub 2} progeny

    SciTech Connect (OSTI)

    Ikeda, Masahiko [University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka, 422 8526 (Japan) and CREST, Japan Science and Technology Corporation, Kawaguchi, 332-0012 (Japan)]. E-mail: ikedam@ys2.u-shizuoka-ken.ac.jp; Tamura, Masashi [University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka, 422 8526 (Japan); Yamashita, Junko [University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka, 422 8526 (Japan); Suzuki, Chinatsu [University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka, 422 8526 (Japan); Tomita, Takako [University of Shizuoka, Graduate School of Nutritional and Environmental Sciences, 52-1, Yada, Shizuoka, 422 8526 (Japan); CREST, Japan Science and Technology Corporation, Kawaguchi, 332-0012 (Japan)

    2005-08-15

    The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F{sub 1}) and the sex ratio of the subsequent generation (F{sub 2}) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F{sub 1}) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissue on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F{sub 2} offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F{sub 1}), leading to changes in the sex ratio of the subsequent generation (F{sub 2})

  1. ALSNews Vol. 362

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

    2 ALSNews Vol. 362 Print Tuesday, 24 March 2015 14:29 Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now

  2. ALSNews Vol. 362

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

    2 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation of the molecular

  3. ALSNews Vol. 362

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

    Bioscience ALSNews Vol. 362 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever

  4. ALSNews Vol. 362

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

    2 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation of the molecular

  5. ALSNews Vol. 362

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

    ALSNews Vol. 362 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation of

  6. Risk Group and Biosafety Level Definitions

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

    Group and Biosafety Level Definitions European Economic Community (DIRECTIVE 93/88/EEC, Oct. 1993) (1) Group 1 biological agent means one that is unlikely to cause human disease; (2) Group 2 biological agent means one that can cause human disease and might be a hazard to workers; it is unlikely to spread to the community; there is usually effective prophylaxis or treatment available; (3) Group 3 biological agent means one that can cause severe human disease and present a serious hazard to

  7. ORISE: Recent Graduate Research Experiences - Krystina Addorisio

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

    Krystina Addorisio Researcher works to protect nation's food agriculture Krystina Assorisio Forensic scientist Krystina Addorisio, pictured right, has spent the last three years researching a vaccine for animal diseases such as foot-and-mouth-a contagious disease that affects cows, pigs and sheep-at the U.S. Department of Homeland Security's Plum Island Animal Disease Center. Click image to enlarge. Each morning, Krystina Addorisio commutes by ferry to work on a small island-the subject of some

  8. Is Primary Prostate Cancer Treatment Influenced by Likelihood of

    Office of Scientific and Technical Information (OSTI)

    Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study (Journal Article) | SciTech Connect Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study Citation Details In-Document Search Title: Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study Purpose: To

  9. Cardiovascular and Interventional Radiological Society of Europe Guidelines

    Office of Scientific and Technical Information (OSTI)

    on Endovascular Treatment in Aortoiliac Arterial Disease (Journal Article) | SciTech Connect Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease Citation Details In-Document Search Title: Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease PurposeThese guidelines are intended for use in assessing the standard for technical success

  10. Forecasting Flu

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

    Forecasting Flu March 6, 2016 Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? Using real-time data from Wikipedia and social media, Sara del Valle and her team from Los Alamos National Laboratory have developed a global disease-forecasting system that will improve the way we respond to epidemics. Using this model, individuals and public health officials can monitor

  11. Faces of Science: Harshini Mukundan

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    Harshini Mukundan March 20, 2015 Leaving her mark on infectious disease Harshini Mukundan is a scientist and team leader at the Los Alamos National Laboratory, working on the development of diagnostic and surveillance strategies for emerging infectious diseases and drug-resistant organisms. Describing her passion for infectious disease research, she says, "Every small incident in your life leaves its mark on you, and that mark influences your decisions in every phase of life. Growing up in

  12. Isotopes for cancer and cardiac care

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

    Isotopes for cancer Isotopes for cancer and cardiac care Eva Birnbaum is interviewed on KSFR radio on the Lab's Isotope Program February 4, 2016 hot cell facility A worker uses remote manipulator arms to handle a highly radioactive target inside the Lab's radiochemistry hot cell facility. Isotopes from Los Alamos are used for the diagnosis of cardiac disease, for the calibration of PET scanners which in turn diagnose cancer, neurological disease, inflammatory diseases, trauma, and other

  13. PHOTOS: 10 Years, 10 Breakthroughs at Argonne's Fastest Supercomputer |

    Energy Savers [EERE]

    Department of Energy PHOTOS: 10 Years, 10 Breakthroughs at Argonne's Fastest Supercomputer PHOTOS: 10 Years, 10 Breakthroughs at Argonne's Fastest Supercomputer February 24, 2016 - 12:46pm Addthis Understanding the molecular basis of Parkinson&#039;s disease 1 of 10 Understanding the molecular basis of Parkinson's disease Researchers ran simulations to understand how several proteins connected with Parkinson's disease interact to cause the degenerative neurological disorder. The findings

  14. Platinum/Chromium-Based Stents Approved for Treatment of Peripheral Artery

    Energy Savers [EERE]

    Disease | Department of Energy Platinum/Chromium-Based Stents Approved for Treatment of Peripheral Artery Disease Platinum/Chromium-Based Stents Approved for Treatment of Peripheral Artery Disease November 14, 2012 - 12:00pm Addthis Washington, DC - A new stent that incorporates an innovative metal alloy developed by scientists at Boston Scientific Corporation and the U.S. Department of Energy (DOE) has received European approval for use in the treatment of certain peripheral arterial

  15. ORISE: ORISE to develop needs assessment plan to support CDC...

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

    and Education (ORISE) will design and carry out a needs assessment plan for the Center for Disease Control and Prevention's (CDC) Advanced Molecular Detection and Response to ...

  16. DOE's Office of Science Awards 18 Million Hours of Supercomputing...

    Office of Environmental Management (EM)

    Projects to be supported by INCITE in the coming year include: the design of more efficient aircraft and engines learning more about the molecular basis of Parkinson's Disease ...

  17. Steap3

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

    or overexpression of Steap proteins is associated with a range of diseases, from anemia to prostate cancer. In the current study, the team solved the structure of the...

  18. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    (2) residues (2) resolution (2) sympathomimetics (2) antibiotics (1) biology (1) biophysics (1) biosynthesis (1) carboxylic acids (1) catalysts (1) diseases (1) drugs (1) ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... (2) proteins (2) sympathomimetics (2) targets (2) alkaloids (1) biochemistry (1) biophysics (1) central nervous system (1) codeine (1) dimers (1) diseases (1) endorphins (1) ...

  20. Jefferson Lab Weekly Briefs November 25, 2015 | Jefferson Lab

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    and Shutdown Days, Jefferson Lab closed Environment, Safety, Health & Quality Safe Turkey Tips from the CDC The Centers for Disease Control and Prevention offer food safety...

  1. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    other invaders from outside our bodies can be deadly foes that bring disease and death. In either case, understanding how bacteria multiply and grow not only increases our...

  2. A Fullerene that Breaks the Rules

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    vehicle for delivering radiotracers for imaging or radiopharmaceuticals for treatment of diseases. Fullerenes also have a high electron affinity, and show great promise as...

  3. Structure of GDNF Family Ligand Artemin Complexed with Its GFRa3...

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

    motor neurons has stimulated interest in their use for the treatment of neurodegenerative diseases such as Parkinson's. These structurally related neurotrophic factors signal by...

  4. Aurora

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

    that benefit humanity the most. From finding alternative energy sources to treating diseases to developing high-tech materials-the research done on leadership-class machines...

  5. ORISE Undergraduate Student Research Experiences: Christopher...

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

    research. It is mostly used in human genome research, which includes the study of genetics and DNA. The genomic information is essential to understanding diseases. It is also...

  6. Enzyme Structure Provides Insights into Cancer and Aging

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    protein are responsible for three different human diseases: in xeroderma pigmentosum (XP), extreme sensitivity to sunlight promotes cancer; Cockayne syndrome (CS) involves...

  7. DOE Awards Over a Billion Supercomputing Hours to Address Scientific...

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

    in oceans, and simulate clouds on a global scale Biology, including understanding protein membranes to improve drug discovery, diagnostics and better treatment of diseases. ...

  8. Cynthia Phillips, ground-breaking expert in plasma waves &...

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

    type of neuroendocrine tumor that eventually spread to her liver and then her lungs. She fought hard against the disease - researching the latest treatments and even...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Liu, Hongliang Tianjin Center for Disease Control and ... improves the predictive power at collider energies. ... We develop a theoretical model to investigate the Bragg ...

  10. Information Sciences and Technology

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

    file systems Bioinformatics Infectious disease surveillance Climate change and energy security Smart grids Learn more about our Information Science and Technology capabilities

  11. Applications of molecular replacement to G protein-coupled receptors...

    Office of Scientific and Technical Information (OSTI)

    Despite their profound importance in human health and disease, structural information ... OSTI Identifier: 22347800 Resource Type: Journal Article Resource Relation: Journal Name: ...

  12. WHO Statistical Information System (WHOSIS) | Open Energy Information

    Open Energy Info (EERE)

    Classification of Diseases (ICD-10), International Classification of Impairments, Disabilities and Handicaps (ICIDH) Links to other sources of health-related statistical...

  13. The Biological Implications of the PP2A Crystal Structure

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

    groups are not removed in needed situations) is associated with multiple human cancers, Alzheimer's Disease, and increased susceptibility to pathogen infections. To shed light on...

  14. Tracking Living Cells as They Differentiate in Real Time

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

    view of how promising drugs act within specific cells. Some of these projects will target Alzheimer's disease, macular degeneration of the retina in diabetes, and mitochondrial...

  15. New Crystal Structures Lift Fog around Protein Folding

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

    incorrect or "misfolding" of proteins has been linked to many diseases, including Alzheimer's, Parkinson's, and some forms of cancer. So far, however, a complete...

  16. AlumniLink: January 2015

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

    Software speeds detection of diseases and cancer-treatment targets Alumni spotlight Ni Ni: University of California - Los Angeles Francesco Grilli: Karlsruhe Institute of...

  17. Recent News from the National Labs | Department of Energy

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

    medical isotopes that are particularly useful in diagnosing and treating cancer and other diseases. In this 1957 photo, a researcher works on the south face of the...

  18. 1

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

    spread of disease August 15, 2011 LOS ALAMOS, New Mexico, August 15, 2011-Connecting social media and epidemiological research, a new study by Los Alamos National Laboratory...

  19. Profile for Sara Y. Del Valle

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

    scale. Studying the role of social behavior on disease dynamics, including the impact of social media on behavior and developing computational models to study those impacts....

  20. Science On Tap

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    "The unnecessary and uncontrolled use of antibiotics and the use of antibiotics in food animals to prevent, control and treat disease and for promoting growth are only some...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structural Basis of Chronic Beryllium Disease: Linking Allergic Hypersensitivity and Autoimmunity Clayton, Gina M. ; Wang, Yang ; Crawford, Frances ; Novikov, Andrey ; Wimberly, ...

  2. Studying Amyotrophic Lateral Sclerosis at the APS

    ScienceCinema (OSTI)

    Gelfand, Paul; Miller, Lisa

    2014-06-05

    Researchers from Brookhaven National Lab come to Argonne's Advanced Photon Source to study Amyotrophic Lateral Sclerosis, commonly known as Lou Gehrig's disease.

  3. Potential Implications for Cataract Formation - Redox Changes...

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

    National Institutes of Health) Numerous diseases, as well as aging itself, are linked to uncontrolled oxidative processes that lead to irreversible damage and ultimately...

  4. ORISE: CHEMPACK Mapping Application | How ORISE is Making a Difference

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

    Centers for Disease Control and Prevention's (CDC) CHEMPACK program in keeping track of nerve antidote cache sites and containers. CHEMPACK, a component of the federal Strategic...

  5. ALSNews Vol. 362

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

    disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    diseases (2) mutants (2) segregation (2) transcription (2) amplification (1) bacteria (1) basic biological sciences single nucleotide polymorphism, snp, indel, comparative...

  7. Simultaneous cryo x-ray ptychographic and fluorescence microscopy...

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

    attached therapeutic or diagnostic agents, help elucidate the roles of trace metals in cell development, and further the study of diseases where trace metal misregulation is...

  8. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    Converting energy to medical progress nuclear medicine NONE RADIOLOGY AND NUCLEAR MEDICINE DIAGNOSIS DISEASES GAMMA CAMERAS GENETICS NUCLEAR MEDICINE PATIENTS RADIATION DETECTION...

  9. Substrate Recognition Strategy for Botulinum Neurotoxin

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

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By...

  10. Genomics and Systems Biology

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    systems: * Understanding the dynamics and treatments of viral diseases, such as HIV, influenza, and hepatitis. * Explore the complex soil community of bacteria and fungi using...

  11. Brain Receptor Structures Key to Future Therapeutics

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

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in America, it is more important than ever to discover ways to treat or prevent diseases...

  12. Beryllium Information | The Ames Laboratory

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

    Beryllium Report 2001 Beryllium Report 2008 Beryllium Report 2010 Beryllium Report 2011 Beryllium News Release 6-5-09 Beryllium Fact Sheet Chronic Beryllium Disease Prevention Plan...

  13. Former Worker Medical Screening Program Related Documents & Links...

    Office of Environmental Management (EM)

    Related Documents & Links Related Documents & Links Beryllium Information-ORISE Chronic Beryllium Disease Information-National Jewish Health Department of Energy Human...

  14. ORISE: Worker Health Studies - Beryllium Testing Laboratory

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

    or manufacturing activities can cause sensitivity in some persons that may lead to chronic beryllium disease. The Oak Ridge Institute for Science and Education (ORISE)...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    acceleration (4) damping (4) linear accelerators (4) neoplasms (4) prostate (4) digestive system (3) diseases (3) focusing (3) glands (3) hazards (3) medicine (3) nuclear medicine ...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... neoplasms (8) multivariate analysis (5) carcinomas (4) organs (4) pancreas (4) digestive system (3) diseases (3) endocrine glands (3) glands (3) medicine (3) metastases (3) ...

  17. SEQUEDEX

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

    diseases (whether arising from bacteria, parasites, or viruses; characterizing gut, oral and skin microbiomes of humans, livestock, and pets; metagenomics of soils, rivers,...

  18. Wellness Services | The Ames Laboratory

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

    wellness services are available for Ames Laboratory employees: Weight monitoring Blood pressure monitoring Information on medications, diseases, treatments and other health...

  19. Sandia National Laboratories: News: Publications: Lab News

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

    to other bacteria. These opportunistic bacteria can grow on hospital surfaces or in lungs and tissues. The Centers for Disease Control and Prevention says about one in 25...

  20. Savannah River Ecology Laboratory Annual Technical Progress Report

    Office of Scientific and Technical Information (OSTI)

    include habitat loss and degradation, introduction of invasive species, environmental pollution, disease, global climate change, and unsustainable commercial use. The conclusion...

  1. Medical Screening Protocol for the Former Worker Medical Screening...

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

    recommendations; repeat CT scan offered on an annual basis after initial baseline Welding Lung Asthma Chronic obstructive lung disease Respiratory symptoms...

  2. Bioscience

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

    bioscience solutions to national security threats such as disease, energy scarcity, and climate change Biofuels to epidemics Genomes to ecosystems Experimental science to...

  3. Faces of Science: Sara Del Valle

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

    Sara Del Valle March 4, 2015 Modeling infectious disease with mathematics While growing up, Sara Del Valle watched her parents tend to people suffering from infectious disease. 1:03 Faces of Science: Sara Del Valle Later in life she discovered her love for mathematics, but always in the back of her mind was her desire to help stop the spread of infectious disease. As a Los Alamos scientist, Sara works with her team to develop mathematical and computer models to study diseases such as smallpox,

  4. http://www.bls.gov/news.release/osh.nr0.htm

    National Nuclear Security Administration (NNSA)

    ... compared to 2008--led by a decline among the 'Skin diseases' category which accounted for nearly 47 percent of the decline in illness cases among private industry establishments. ...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    changes (1) crystal structure (1) diseases (1) functionals (1) gtp-ases (1) hormones (1) materials science (1) proteins (1) regulations (1) spectroscopy (1)...

  6. 2011 - 10 | Jefferson Lab

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

    October 2011 Thu, 10/27/2011 - 2:00pm Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases

  7. SLAC Snapshot | Department of Energy

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

    makes them important for both diseases trying to infect them and the drugs devised to fight them. These proteins are also exceptionally difficult to image - scientists can spend...

  8. 1

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

    Supporting biosurveillance via the web January 28, 2015 Los Alamos science team gathers a virtual biological toolkit for international disease outbreak response LOS ALAMOS, N.M.,...

  9. Multi-analyte analysis of saliva biomarkers as predictors of...

    Office of Scientific and Technical Information (OSTI)

    The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal andor peri-implant disease. More specifically, the invention...

  10. Frontiers in Science talks to explore new strategies for diagnosing...

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

    for diagnosing challenging diseases Harshini Mukundan discusses the re-emergence of tuberculosis in a series of lectures called "The Microbe Strikes Back: The Return of...

  11. Consent Order, Lawrence Livermore National National Security, LLC- WCO-2010-01

    Broader source: Energy.gov [DOE]

    Issued to Lawrence Livermore National Security, LLC for deficiencies associated with the Lawrence Livermore National Laboratory Chronic Beryllium Disease Prevention Program

  12. Relations between health indicators and residential proximity to coal mining in West Virginia

    SciTech Connect (OSTI)

    Hendryx, M.; Ahern, M.M.

    2008-04-15

    We used data from a survey of 16493 West Virginians merged with county-level coal production and other covariates to investigate the relations between health indicators and residential proximity to coal mining. Results of hierarchical analyses indicated that high levels of coal production were associated with worse adjusted health status and with higher rates of cardiopulmonary disease, chronic obstructive pulmonary disease, hypertension, lung disease, and kidney disease. Research is recommended to ascertain the mechanisms, magnitude, and consequences of a community coal-mining exposure effect.

  13. Draft Environmental Assessment for Direct Final Rule, 10 CFR...

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

    ... the eyes and respiratory tract, and liver and kidney damage. ... asthma; development of chronic bronchitis; irregular ... and, premature death in people with heart or lung disease. ...

  14. Picture of the Week: Forecasting Flu

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

    3 Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? March 6, 2016 flu epidemics modellled using social media Watch the video on YouTube. Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? Using real-time data from Wikipedia and social media, Sara del

  15. I T E L I N E S S A

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

    ... The Centers for Disease Control and Prevention (CDC) recommends that chil- dren receive vaccines against diphtheria, tetanus, pertussis (whooping cough), measles, mumps, rubella, ...

  16. Microsoft Word - Zn-DTPA Insert_2 Pages.doc

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

    ... pelvic pain. Two individuals experienced cough andor wheezing with nebulized Ca-DTPA ... to aerosolized treatment (ho lung disease, cough, dyspnea, chest tightness, wheezing)? ...

  17. Microsoft Word - Ca-DTPA Insert_2 Pages.doc

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

    ... Cough andor wheezing were experienced by 2 individuals receiving nebulized Ca-DTPA, one ... to aerosolized treatment (ho lung disease, cough, dyspnea, chest tightness, wheezing)? ...

  18. Audit Report: DOE/IG-0917 | Department of Energy

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

    Administration (NNSA) operate multiple laboratory facilities in accordance with various biosafety levels (BSL) established by the Centers for Disease Control and Prevention. ...

  19. General Counsel Legal Interpretation Regarding Medical Removal...

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

    Counsel Legal Interpretation Regarding Medical Removal Protection Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program General Counsel Legal ...

  20. Office of Environmental Management's Hanford Site Awards $99M...

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

    Their work for the Energy Department on this contract will support epidemiological studies of current and former Hanford site workers, the Chronic Beryllium Disease Prevention ...

  1. In Vitro Genotoxicity of Gasoline and Diesel Engine Vehicle Exhaust...

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

    Compound Materials 2002 DEER Conference Presentation: U.S. Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health PDF icon ...

  2. Worker Safety and Health Enforcement Documents | Department of...

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

    ... Worker Safety and Health Enforcement Consent Order issued to Battelle Memorial Institute for deficiencies associated with the Chronic Beryllium Disease Prevention Program at DOE's ...

  3. Semiannual Report to Congress, October 1, 2007 - March 31, 2008

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

    ... We made recommendations to help the Department prepare for and respond to emerging threats. (DOEIG-0787) Concerns Over the Chronic Beryllium Disease Prevention Program at the Y-12 ...

  4. Foreign Travel Health & Wellness Information | Department of...

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

    Foreign Travel Checklist MEDEX Plus Travel Information from the Office of Management Related Links World Health Organization Centers for Disease Control & Prevention Department of ...

  5. In Vitro Genotoxicity of Particulate and Semi-Volatile Organic...

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

    Vehicles Operated at 30F 2003 DEER Conference Presentation: Centers for Disease Control and Prevention PDF icon 2003deerwallace.pdf More Documents & Publications In Vitro ...

  6. DOE F 440.1 | Department of Energy

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

    PDF icon 10 CFR PART 850 - APPENDIX A CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM INFORMED CONSENT FORM More Documents & Publications Beryllium Screening - Informed Choice ...

  7. Consent Order, Lawrence Livermore National National Security...

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

    Issued to Lawrence Livermore National Security, LLC for deficiencies associated with the Lawrence Livermore National Laboratory Chronic Beryllium Disease Prevention Program On ...

  8. One Vaccine Leads to Another

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

    One Vaccine Leads to Another Print Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines...

  9. Staying active - for life | Y-12 National Security Complex

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

    averaged over 46 minutes per day, which meets and exceeds recommendations for overall health and minimizing risk of chronic disease, and far exceeds national averages for...

  10. Medical treatments, fuel sources from studying elusive enzyme

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    potential to aid in treatment of peptic ulcers, acid reflux disease, or conversion of woody waste into transportation fuels. April 3, 2012 Using neutrons at Los Alamos National...

  11. Photo of the Week: We Mustache You a Question | Department of...

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

    medical isotopes that are particularly useful in diagnosing and treating cancer and other diseases. In this 1957 photo, a researcher works on the south face of the...

  12. Breakthrough Los Alamos software is available for licensing

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

    Alamos software is available for licensing Sequedex speeds detection of diseases and cancer-treatment targets February 1, 2015 Thanks to the new technology, laptop computers can...

  13. 1

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

    Software speeds detection of diseases and cancer-treatment targets December 1, 2014 New technology puts bioinformatics within easy reach of health-care professionals, researchers...

  14. Microsoft PowerPoint - Briefings_Galan

    Office of Environmental Management (EM)

    performed daily in the United States, including diagnosis of heart disease, treating cancer, and studying organ structure and function. - 1 in 13 residents will receive nuclear...

  15. Microsoft Word - EPO Medicare Retiree Highlight Sheet_010116...

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

    4 Ambulance: Nonemergency Air Transfer (between facilities) 10% after deductible 4 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  16. Today's tuberculosis

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

    part of a larger effort to diagnose a range of diseases, including influenza and breast cancer, and relies on the participation of biologists, chemists, engineers and materials...

  17. BlueChoice

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

    4 Ambulance: Nonemergency Air Transfer (between facilities) 10% after deductible 4 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  18. Microsoft Word - PPO Medicare Retiree Highlight Sheet_010116...

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

    and Lodging: Benefits are available when these services are related to case-managed Cancer Services or Congenital Heart Disease if patient is receiving treatment from a Blue...

  19. Microsoft Word - hdhp-active-non-medicare-retirees-highlights...

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

    Physician and Other Professional Provider Charges ) 10% after In-Network deductible 3 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  20. BlueChoice

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

    and Lodging: Benefits are available when these services are related to case-managed Cancer Services or Congenital Heart Disease if patient is receiving treatment from a Blue...

  1. BlueChoice

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

    Physician and Other Professional Provider Charges ) 10% after In-Network deductible 3 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  2. Fellows

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

    recognition, sensors inspired by nature, and new approaches for the diagnosis of cancer and infectious disease. Swanson has authored over 260 articles in peer-reviewed...

  3. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... States) USDOE Office of Electricity Delivery and Energy ... genetic information for these and other pertinent disease associated genes. Full Text Available August 2015 Transient ...

  4. Geek-Up[6.3.2011]: Inked PV, Diagnostic Tools and Tough Microscopes...

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

    ... Insight for Potential Disease Treatments DOE Laboratories Help Develop Promising New Cancer Fighting Drug, Vemurafenib Flora Meilleur prepares protein solutions for structural ...

  5. Microsoft Word - Contract Administration Long Testimony _FINAL...

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

    computing, and developing treatments for cancer and other diseases. 2 Despite these successes, contract administration at the Department has not been without its problems. ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... in the detection and isolation of sialylated glycoconjugates, such as those associated with pathogen adhesion as well as those characteristic of several diseases including cancer. ...

  7. U.S. Department of Energy A Decade of Discovery Documents Advances...

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

    Book vividly illustrates the vital importance of the Department's National Laboratories WASHINGTON, DC - Finding new and better ways to detect and treat cancer, Parkinson's disease ...

  8. Search for: All records | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    ... is a tripeptidic inhibitor of the proteolytic activity of the proteasomes, enzyme complexes implicated in several neurodegenerative diseases and other disorders, including cancer. ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... models and biological reagents will significantly improve our ability to study cell-signaling involved in host-pathogen interactions and other diseases such as cancer. ...

  10. DOE/EH-0467 Interview with Dr. ...

    Office of Scientific and Technical Information (OSTI)

    ... relationship of human chromosomes to cancer, * the biological and medical effects o f ionizing radiation, with particular reference to cancer, leukemia, and genetic diseases, and ...

  11. Department of Energy Planning Cookstoves Research, Releases Biomass...

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

    indoor air pollution from these cooking devices is responsible for the deaths of 1.6 million people every year from pneumonia, chronic respiratory disease and lung cancer. ...

  12. Roger D. Kornberg Polymerase, DNA, RNA, and Transcription

    Office of Scientific and Technical Information (OSTI)

    also helps explain how the process sometimes goes awry, leading to birth defects, cancer and other diseases.' - Edited excerpt from 2006 Nobel Prize in Chemistry Resources ...

  13. The DOE Security Plan for the Energy Employees Occupational Illness...

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

    vendor facility may be eligible for benefits under EEOICPA. Part B of EEOICPA provides compensation to workers with beryllium disease, silicosis, or radiation-induced cancer. ...

  14. Crystal structure of N-{N-[N-acetyl-(S)-leucyl]-(S)-leucyl}norleucinal...

    Office of Scientific and Technical Information (OSTI)

    is a tripeptidic inhibitor of the proteolytic activity of the proteasomes, enzyme complexes implicated in several neurodegenerative diseases and other disorders, including cancer. ...

  15. Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas...

    Office of Scientific and Technical Information (OSTI)

    in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. ...

  16. LACED

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

    detect and defeat potential threats - 021115 Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now...

  17. PowerPoint Presentation

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

    disease biomarkers in human biological samples * Point-of-Care diagnostics amenable to health clinics and field sensing applications * Integrated miniaturized electronics, optical...

  18. Decision Models for Integrating Energy/Water

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

    ... This tension must be resolved because all three uses are essential for our survival. Drought, famine, poverty, terrorism, disease, conflict, social unrest and overall state failure ...

  19. Research News July 2015, Issue 10

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

    ... persistence, and imagination they can solve the problems facing humanity like hunger, poverty, war, and disease; that we really know little about the world around us; that natural ...

  20. Infrastructure Security EXCEPTIONAL SERVICE IN THE NATIONAL INTEREST

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

    Consistent and Sustainable Delivery of Resources Drought, famine, poverty, terrorism, disease, conflict, social unrest, and overall state failure are just a few of the challenges ...

  1. Today, DOE's Joint Genome Institute (a

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

    in forms of kidney disease, prostate and colorectal cancer, leukemia, hypertension, diabetes, and atherosclerosis. The JGI's DNA Production Genomics Facility is one of the most...

  2. SSRL HEADLINES Sep 2012

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

    melanoma, and degenerative diseases like multiple sclerosis, Alzheimer's and Type 2 diabetes. Understanding of how Wnt proteins bind and activate Frizzled receptors is important...

  3. Structure of the ESCRT-II endosomal trafficking complex

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

    D. Emr 2 & James H. Hurley 1 1 Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of...

  4. Structural Studies of Nitric Oxide Synthase Inhibitor Complexes...

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

    can cause inflammation, rheumatoid arthritis, inflammatory bowel disease, immune-type diabetes, stroke, and cancer. The three NOS isozymes are structurally similar and share...

  5. Stanford Synchrotron Radiation Lightsource

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

    melanoma, and degenerative diseases like multiple sclerosis, Alzheimer's and Type 2 diabetes. Understanding of how Wnt proteins bind and activate Frizzled receptors is important...

  6. Structure of the ESCRT-II Endosomal Trafficking Complex

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

    D. Emr2 & James A Hurley1 1 Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of...

  7. Sleep Assessment

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

    history? Do you have a family history of any of the following? (Please indicate) Diabetes Heart disease High blood pressure Stroke Sleep apnea Restless leg syndrome Insomnia...

  8. SREL Reprint #3151

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

    has now shown to represent an important animal model for studies of obesity and diabetes, two diseases which have now become epidemic in many human populations worldwide...

  9. ORISE: Health Disparity Interventions

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

    issues that disproportionately affect them, such as HIVAIDS, cardiovascular disease, diabetes, immunization, cancer and infant mortality. Equally important is improving access to...

  10. Gut microbes affect circadian rhythms in mice, study says | Argonne...

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

    was supported by the National Institute of Health's (NIH) National Institute of Diabetes and Digestive and Kidney Diseases; the Peter and Carol Goldman Family Research Fund;...

  11. 35 Breakthroughs

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

    chromosomes 5, 16, and 19, which are regions of the genetic library implicated in diabetes, atherosclerosis, asthma, and other diseases. 15 Brought safe drinking water to...

  12. Accident Investigation of the June 1, 2013 Stairway Fall Resulting...

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

    show that examinations were conducted for employees with various illnesses, such as diabetes and Alzheimer's disease, which occurred off the job 9 . The Board believes that if a...

  13. Los Alamos and Malaysian University collaborate to find genetic...

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

    such as apnea, middle ear disease, speech delay and articulation problems, obesity, and dental crowding. Sequencing the genomes of people with achondroplasia provides...

  14. July/2002

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

    entitlement varies depending upon the disease and the facility where an indi- vidual worked. The act also covers some employees of suppliers to the above facilities, including...

  15. Celebration of the Genome - Secretary Abraham Statement 4/10...

    Office of Scientific and Technical Information (OSTI)

    in forms of kidney disease, prostate and colorectal cancer, leukemia, hypertension, diabetes and atherosclerosis. Now, DOE once again is pioneering discovery-class science. ...

  16. Occupation Codes

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

    ... Includes: Abscess of breast, adrenal gland disorders, benign mammary dysplasias, cystic fibrosis, cystitis, diabetes, diseases and disorders of the genital tract, endocrine ...

  17. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    2015 Non-enzymatic glycation of alpha-crystallin as an in vitro model for aging, diabetes and degenerative diseases Karumanchi, Devi Kalyan ; Karunaratne, Nuwan ; Lurio, ...

  18. Department of Energy - Chromosomes News Release 4/13/2000

    Office of Scientific and Technical Information (OSTI)

    Information May Lead to Treatments for Kidney Disease, Diabetes and Prostate and ... cancer, leukemia, hypertension, diabetes and atherosclerosis. "Three chapters in ...

  19. November 6, 2008; HSS/Union Working Group Meeting on Aging Workforce...

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

    of chronic diseases usually associated with aging * Increases noted in hypertension, diabetes, and musculoskeletal conditions. * Findings point out need to address emerging health ...

  20. DOE Researchers Achieve Important Genetic Breakthroughs to Help...

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

    started a project to investigate how to use the "RNA machines" to increase the safety and efficacy of medicine therapies to treat diseases, including diabetes and Parkinson's. ...

  1. U.S. Department of Energy Office of Health, Safety, and Security...

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

    ... This report also examined the impact of two chronic diseases, diabetes and hypertension, ... A major cause of hypertension and diabetes has been attributed to the epidemic of obesity. ...

  2. Breaking the Biological Barriers to Cellulosic Ethanol, June...

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

    ... scientist at NIH National Institute of Diabetes and Digestive and Kidney Diseases until ... cells with emphasis on obesity and diabetes, and bioinformatics and functional ...

  3. November 6, 2008; HSS/Union Working Group Meeting on Aging Workforce...

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

    ... and skilled but aging work force; older workers are becoming a large percentage of the work force; absence rates for diseases such as diabetes and hypertension are increasing". ...

  4. OSTI, US Dept of Energy, Office of Scientific and Technical Informatio...

    Office of Scientific and Technical Information (OSTI)

    This multi-scale visualization methodology is helping researchers to better predict and understand aneurysm ruptures as well as other blood-related diseases like diabetes, sickle ...

  5. OSTI, US Dept of Energy, Office of Scientific and Technical Informatio...

    Office of Scientific and Technical Information (OSTI)

    ... promise of gene therapies for such diseases as cystic fibrosis, sickle cell anemia, diabetes, and cancer, + and the prospect of using genetic techniques to harness microbes that ...

  6. Geek-Up[08.20.10] -- Turning Trash Bags into Battery Anodes and...

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

    ... This important discovery could help scientists and doctors better understand the impact of these organisms on diseases like diabetes. Learn how > Scientists at Ames Laboratory have ...

  7. SF256

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

    ... wcomplete recovery 83 - Blood diseases (e.g., sickle cell anemia, hemophilia) 84 - Diabetes 86 - Pulmonary or respiratory conditions (e.g., tuberculosis, asthma, emphysema, ...

  8. Portsmouth/Paducah Project Office

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

    ... external exposure to radiation Kidney, lung, tumors (kidney, brain, liver), ... and Disease Registry IARC International Agency for Research on Cancer D&D ...

  9. Brain Receptor Structures Key to Future Therapeutics

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

    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in ... diseases affecting the brain and its ability to make new connections and recall memories. ...

  10. Forensic analysis of the microbiome of phones and shoes (Journal...

    Office of Scientific and Technical Information (OSTI)

    are shared between individuals inhabiting the same space may be relevant to human health and disease transmission. In this study, two participants sampled the front and back...

  11. Department of Energy Projects Win 36 R&D 100 Awards for 2011...

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

    ... NanoCluster Beacons: The Beacons are superior probes for detecting diseases such as cancers or sickle cell anemia. Inexpensive and easy to use, they allow for personalized ...

  12. Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling

    SciTech Connect (OSTI)

    Lin, Zhoumeng; Fisher, Jeffrey W.; Wang, Ran; Ross, Matthew K.; Filipov, Nikolay M.

    2013-11-15

    Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous environmental contaminant, and a potential developmental toxicant. To quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic models were developed for rat dams, fetuses and neonates. These models were calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral gavage; 5 mg/kg) to ATR followed by model evaluation against other available rat data. Model simulations corresponded well to the majority of available experimental data and suggest that: (1) the fetus is exposed to both ATR and its major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than maternal plasma or fetal levels, while lactational exposure to ATR is minimal, and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up until mid-lactation. To test the model's cross-species extrapolation capability, a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral gavage; 5 mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific parameters, the model predictions fitted well with the measured data, including placental ATR/DACT levels. However, fetal concentrations of DACT were overestimated by the model (10-fold). This overestimation suggests that only around 10% of the DACT that reaches the fetus is tissue-bound. These rodent models could be used in fetal/neonatal tissue dosimetry predictions to help design/interpret early life toxicity/pharmacokinetic studies with ATR and as a foundation for scaling to humans. - Highlights: • We developed PBPK models for atrazine in rat dams, fetuses, and neonates. • We conducted pharmacokinetic (PK) study with atrazine in pregnant mice. • Model predictions were in good agreement with experimental rat and mouse PK data. • The fetus is exposed to atrazine/its main metabolite at levels similar to the dam. • The nursing neonate is exposed primarily to atrazine's main metabolite DACT.

  13. A role for glutathione, independent of oxidative stress, in the developmental toxicity of methanol

    SciTech Connect (OSTI)

    Siu, Michelle T.; Shapiro, Aaron M.; Wiley, Michael J.; Wells, Peter G.

    2013-12-15

    Oxidative stress and reactive oxygen species (ROS) have been implicated in the teratogenicity of methanol (MeOH) in rodents, both in vivo and in embryo culture. We explored the ROS hypothesis further in vivo in pregnant C57BL/6J mice. Following maternal treatment with a teratogenic dose of MeOH, 4 g/kg via intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase 6 h later in embryonic ROS formation, measured by 2?,7?-dichlorodihydrofluorescin diacetate (DCFH-DA) fluorescence, despite an increase observed with the positive control ethanol (EtOH), nor was there an increase in embryonic oxidatively damaged DNA, quantified as 8-oxo-2?-deoxyguanosine (8-oxodG) formation. MeOH teratogenicity (primarily ophthalmic anomalies, cleft palate) also was not altered by pre- and post-treatment with varying doses of the free radical spin trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted maternal hepatic and embryonic GSH, and enhanced some new anomalies (micrognathia, agnathia, short snout, fused digits, cleft lip, low set ears), but not the most common teratogenic effects of MeOH (ophthalmic anomalies, cleft palate) in this strain. These results suggest that ROS did not contribute to the teratogenic effects of MeOH in this in vivo mouse model, in contrast to results in embryo culture from our laboratory, and that the protective effect of GSH in this model may arise from its role as a cofactor for formaldehyde dehydrogenase in the detoxification of formaldehyde. - Highlights: • In vivo, a free radical scavenger did not block methanol (MeOH) teratogenesis. • MeOH did not increase embryonic reactive oxygen species formation or DNA oxidation. • MeOH teratogenesis was enhanced by glutathione (GSH) depletion. • GSH may protect as the cofactor for formaldehyde dehydrogenase (ADH3). • Formaldehyde may be a ROS-independent proximate teratogenic species in vivo.

  14. Method of identifying plant pathogen tolerance

    DOE Patents [OSTI]

    Ecker, J.R.; Staskawicz, B.J.; Bent, A.F.; Innes, R.W.

    1997-10-07

    A process for identifying a plant having disease tolerance comprising administering to a plant an inhibitory amount of ethylene and screening for ethylene insensitivity, thereby identifying a disease tolerant plant, is described. Plants identified by the foregoing process are also described. 7 figs.

  15. Method of identifying plant pathogen tolerance

    DOE Patents [OSTI]

    Ecker, Joseph R. (Erial, NJ); Staskawicz, Brian J. (Castro Valley, CA); Bent, Andrew F. (Piedmont, CA); Innes, Roger W. (Bloomington, IN)

    1997-10-07

    A process for identifying a plant having disease tolerance comprising administering to a plant an inhibitory amount of ethylene and screening for ethylene insensitivity, thereby identifying a disease tolerant plant, is described. Plants identified by the foregoing process are also described.

  16. Harnessing Light in the Fight Against Cancer | Argonne National Laboratory

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

    Against Cancer Medical researchers are looking to target diseases such as cancer at increasingly precise levels, down to the nanoscale. Recent advances in this effort have revealed that molecules triggered by the diseases themselves may well provide the signals necessary to achieve this refinement. PDF icon Nano Sheet_harnessing light

  17. Whole-Genome Sequences of Borrelia bissettii Borrelia valaisiana and Borrelia spielmanii

    SciTech Connect (OSTI)

    Schutzer S. E.; Dunn J.; Fraser-Liggett C. M.; Qiu W.-G.; Kraiczy P.; Mongodin E. F.; Luft B. J.; Casjens S. R.

    2012-01-01

    It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii A14S, and B. bissettii DN127.

  18. ORNL research could lead to new treatment for Parkinson's

    SciTech Connect (OSTI)

    Boyd Evans

    2009-08-12

    Parkinson's disease can be debilitating, and right now, there is no cure. But soon, there could be one more way doctors can help fight off the symptoms of that disease, along with stroke and brain tumors. It's all because of research conducted over the past five years at the Oak Ridge National Laboratory.

  19. Spirometry

    Broader source: Energy.gov [DOE]

    Spirometry, which is also known as pulmonary function testing, is a tool for measuring lung function. Specifically, the test measures the volume (amount) and/or flow (speed) of air that can be inhaled or exhaled. Spirometry testing is a vital component for diagnosing occupational lung diseases and for assessing and monitoring such conditions as asthma and chronic obstructive pulmonary disease.

  20. Tools for Discovery Offer Potential Hope for Huntington’s

    Broader source: Energy.gov [DOE]

    Researchers at the Department of Energy's Oak Ridge National Laboratory (ORNL) are hoping that their study of Huntington’s disease and other diseases like Alzheimer’s and Parkinson’s will not only contribute to a treatment, but perhaps even a remedy for the thousands of sufferers in the U.S.