94 Search Results

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell–cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell–cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. Further, this study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.

AGR 5/6/7 Disassembly and Metrology background, disassembly obervations on graphite holders and fuel compacts, metrology fuel compacts and graphite holders, and summary.

The purpose of the current architectural survey is to record the Nuclear Rocket Development Station (NRDS) district, which is recommended eligible for listing to the NRHP under all four criteria as the testing center for the Rover/NERVA (Nuclear Engine for Rocket Vehicle Application) program from the initial boundary survey in 1956 to the end of nuclear rocket development on January 5, 1973. Resources in the NRDS district were evaluated to determine if they are eligible for listing to the National Register as district contributors. The current survey identified the Reactor Control Point subdistrict to provide a temporal, spatial, and functional framework for organizing the resources involved in the NRDS operations. However, the subdistrict was not evaluated as a potential historic district against the Secretary of Interior’s Significance Criteria.

The purpose of the current architectural survey is to record the Nuclear Rocket Development Station (NRDS) district, which is recommended eligible for listing to the NRHP under all four criteria as the testing center for the Rover/NERVA (Nuclear Engine for Rocket Vehicle Application) program from the initial boundary survey in 1956 to the end of nuclear rocket development on January 5, 1973. Resources within the boundary of the NRDS district were evaluated to determine if they are eligible for listing to the National Register as district contributors. Subdistricts within the larger NRDS district were defined to provide a temporal, spatial, and functional framework for organizing the resources involved in the NRDS operations. However, developing contexts for the individual subdistricts was beyond the scope of the NRDS survey. Therefore, the potentially eligible subdistricts were not individually evaluated under any of the Secretary of Interior’s Significance Criteria for eligibility to the National Register.

The U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO), and the U.S. Department of Energy Environmental Management Nevada Program (EM NV) plan to implement corrective action activities (under the Federal Facility Agreement and Consent Order, agreed to by the State of Nevada) and demolition of the Engine Maintenance, Assembly, and Disassembly (E-MAD) facility and the Test Cell C Historic District. These are major components of the unrecorded Nuclear Rocket Development Station (NRDS) Historic District, which is eligible for inclusion in the National Register of Historic Places (NRHP, National Register). The NRDS is in Area 25 of the Nevada National Security Site (NNSS), formerly known as the Nevada Test Site, in Nye County, Nevada. Demolition and removal of the buildings and accessories constitutes an undertaking subject to review under Section 106 of the National Historic Preservation Act (54 United States Code [USC] § 306101) and its implementing regulations, 36 Code of Federal Regulations (CFR) Part 800.

Nucleosome DNA unwrapping and its disassembly into hexasomes and tetrasomes is necessary for genomic access and plays an important role in transcription regulation. Previous single-molecule mechanical nucleosome unwrapping revealed a low- and a high-force transitions, and force-FRET pulling experiments showed that DNA unwrapping is asymmetric, occurring always first from one side before the other. However, the assignment of DNA segments involved in these transitions remains controversial. Here, using high-resolution optical tweezers with simultaneous single-molecule FRET detection, we show that the low-force transition corresponds to the undoing of the outer wrap of one side of the nucleosome (~27 bp), a process that can occur either cooperatively or noncooperatively, whereas the high-force transition corresponds to the simultaneous unwrapping of ~76 bp from both sides. This process may give rise stochastically to the disassembly of nucleosomes into hexasomes and tetrasomes whose unwrapping/rewrapping trajectories we establish. In contrast, nucleosome rewrapping does not exhibit asymmetry. To rationalize all previous nucleosome unwrapping experiments, it is necessary to invoke that mechanical unwrapping involves two nucleosome reorientations: one that contributes to the change in extension at the low-force transition and another that coincides but does not contribute to the high-force transition.

The significance of circular economy and its integration into core strategies for smart, sustainable, and inclusive growth, is increasingly being recognized by individuals, organisations, and nations in recent times. The term Design for Disassembly (DfD) may conjure up images about the end-of-life of a product or its disposal. However, DfD connects to numerous circularity and sustainability goals over the lifetime of a product or project and can have a large impact on the carbon footprint of the product. The DfD is a product development methodology which is in line with the vision of a circular economy, and supports increase in material efficiency, extends product lifetimes and improves recycling efficiency. Reduction of the imposed environmental risks and impact on the climate, by utilising circularity approaches such as remanufacturing, are tied to lowering of carbon footprint. This paper describes specific and actionable approaches that can be applied by luminaire manufacturers, specifiers, and other players in the lighting industry. The readers will learn about current tools and methodologies that can be used to improve iterative design, as well as measure, assess, and compare products or materials.

The purpose of this code is to disassemble potentially malicious code into benign pieces that can safely be transported via any number of traditional methods without fear of infection.

Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer’s disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. In this work, we have shown that a novel class of oligo-p-phenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-β (Aβ) and α-synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aβ fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aβ40, OPE oxidized only Aβ40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic β-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE’s photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.

The Shieldin complex, composed of REV7, SHLD1, SHLD2, and SHLD3, protects DNA double-strand breaks (DSBs) to promote nonhomologous end joining. The AAA⁺ ATPase TRIP13 remodels Shieldin to regulate DNA repair pathway choice. Here we report crystal structures of human SHLD3–REV7 binary and fused SHLD2–SHLD3–REV7 ternary complexes, revealing that assembly of Shieldin requires fused SHLD2–SHLD3 induced conformational heterodimerization of open (O-REV7) and closed (C-REV7) forms of REV7. We also report the cryogenic electron microscopy (cryo-EM) structures of the ATPγS-bound fused SHLD2–SHLD3–REV7–TRIP13 complexes, uncovering the principles underlying the TRIP13-mediated disassembly mechanism of the Shieldin complex. We demonstrate that the N terminus of REV7 inserts into the central channel of TRIP13, setting the stage for pulling the unfolded N-terminal peptide of C-REV7 through the central TRIP13 hexameric channel. The primary interface involves contacts between the safety-belt segment of C-REV7 and a conserved and negatively charged loop of TRIP13. This process is mediated by ATP hydrolysis-triggered rotatory motions of the TRIP13 ATPase, thereby resulting in the disassembly of the Shieldin complex.