Local Strain Measurement of Kevlar Strand with Fiber Optic Bragg Grating

1987 DuPont manufactured 4560 denier Kevlar/Epoxy Strands were instrumented with nine and three sensors each. Stress tests were performed at 30,45,60,70 and 80% of ultimate strength with dwell times of 10,000 seconds. FBG showed uneven stress levels which is contrary to conventional observation

Strain Measurement during Stress Rupture of Composite Over-Wrapped Pressure Vessel with Fiber Bragg Gratings Sensors

Fiber optic Bragg gratings were used to measure strain fields during Stress Rupture (SSM) test of Kevlar Composite Over-Wrapped Pressure Vessels (COPV). The sensors were embedded under the over-wrapped attached to the liner released from the Kevlar and attached to the Kevlar released from the liner. Additional sensors (foil gages and fiber bragg gratings) were surface mounted on the COPY liner

Coupling Between Lysozyme and Trehalose Dynamics: Microscopic Insights from Molecular-Dynamics Simulations

We have carried out molecular-dynamics simulations on fully flexible all-atom models of the protein lysozyme immersed in trehalose, an effective biopreservative, with the purpose of exploring the nature and extent of the dynamical coupling between them. Our study shows a strong coupling over a wide range of temperatures. We found that the onset of anharmonic behavior was dictated by changes in the dynamics and relaxation processes in the trehalose glass. The physical origin of protein-trehalose coupling was traced to the hydrogen bonds formed at the interface between the protein and the solvent. Moreover, protein-solvent hydrogen bonding was found to control the structural relaxation of the protein. The dynamics of the protein was found to be heterogeneous; the motions of surface and core atoms had different dependencies on temperature and, in addition, the surface atoms were more sensitive to the dynamics of the solvent than the core atoms. From the solvent perspective we found that the dynamics near the protein surface showed an unexpected enhanced mobility compared to the bulk. These results shed some light on the microscopic origins of the dynamical coupling in protein-solvent systems. (c) 2006 American Institute of Physics

Antiviral activity of the EB peptide against zoonotic poxviruses

<p>Abstract</p> <p>Background</p> <p>The EB peptide is a 20-mer that was previously shown to have broad spectrum <it>in vitro </it>activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for <it>in vitro </it>activity against the zoonotic orthopoxviruses cowpox and monkeypox and for <it>in vivo </it>activity in mice against vaccinia and cowpox.</p> <p>Findings</p> <p>In yield reduction assays, EB had an EC₅₀of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC₅₀for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox <it>in vitro </it>by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited <it>in vitro </it>by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no <it>in vivo </it>activity against cowpox in mice.</p> <p>Conclusions</p> <p>While EB did demonstrate some <it>in vivo </it>efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment <it>in vitro </it>than as a therapeutic against orthopoxviruses <it>in vivo</it>.</p

Electrostatic Interactions and Binding Orientation of HIV-1 Matrix Studied by Neutron Reflectivity

AbstractThe N-terminal matrix (MA) domain of the HIV-1 Gag protein is responsible for binding to the plasma membrane of host cells during viral assembly. The putative membrane-binding interface of MA was previously mapped by means of mutagenesis and analysis of its trimeric crystal structure. However, the orientation of MA on membranes has not been directly determined by experimental measurements. We present neutron reflectivity measurements that resolve the one-dimensional scattering length density profile of MA bound to a biomimetic of the native viral membrane. A molecular refinement procedure was developed using atomic structures of MA to determine the orientation of the protein on the membrane. The orientation defines a lipid-binding interface consistent with previous mutagenesis results. The MA protein maintains this orientation without the presence of a myristate group, driven only by electrostatic interactions. Furthermore, MA is found to penetrate the membrane headgroup region peripherally such that only the side chains of specific Lys and Arg residues interact with the surface. The results suggest that electrostatic interactions are sufficient to favorably orient MA on viral membrane mimics. The spatial determination of the membrane-bound protein demonstrates the ability of neutron reflectivity to discern orientation and penetration under physiologically relevant conditions

Characterization of an Extensive Interface on Vitronectin for Binding to Plasminogen Activator Inhibitor-1: Adoption of Structure in an Intrinsically Disordered Region

Copyright © 2019 American Chemical Society. Small-angle neutron scattering (SANS) measurements were pursued to study human vitronectin, a protein found in tissues and the circulation that regulates cell adhesion/migration and proteolytic cascades that govern hemostasis and pericellular proteolysis. Many of these functions occur via interactions with its binding partner, plasminogen activator inhibitor-1 (PAI-1), the chief inhibitor of proteases that lyse and activate plasminogen. We focused on a region of vitronectin that remains uncharacterized from previous X-ray scattering, nuclear magnetic resonance, and computational modeling approaches and which we propose is involved in binding to PAI-1. This region, which bridges the N-terminal somatomedin B (SMB) domain with a large central β-propeller domain of vitronectin, appears unstructured and has characteristics of an intrinsically disordered domain (IDD). The effect of osmolytes was evaluated using circular dichroism and SANS to explore the potential of the IDD to undergo a disorder-to-order transition. The results suggest that the IDD favors a more ordered structure under osmotic pressure; SANS shows a smaller radius of gyration (Rg) and a more compact fold of the IDD upon addition of osmolytes. To test whether PAI-1 binding is also coupled to folding within the IDD structure, a set of SANS experiments with contrast variation were performed on the complex of PAI-1 with a vitronectin fragment corresponding to the N-terminal 130 amino acids (denoted the SMB-IDD because it contains the SMB domain and IDD in linear sequence). Analysis of the SANS data using the Ensemble Optimization Method confirms that the SMB-IDD adopts a more compact configuration when bound to PAI-1. Calculated structures for the PAI-1:SMB-IDD complex suggest that the IDD provides an interaction surface outside of the primary PAI-1-binding site located within the SMB domain; this binding is proposed to lead to the assembly of higher-order structures of vitronectin and PAI-1 commonly found in tissues

The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome

The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.National Institutes of Health (U.S.) (grant U54HG004969)National Institutes of Health (U.S.) (grant U54HG004973)National Institutes of Health (U.S.) (grant U54AI084844)National Institutes of Health (U.S.) (grant U01HG004866)National Institutes of Health (U.S.) (grant R01HG005969)National Institutes of Health (U.S.) (grant R01HG004872)United States. Army Research Office (grant W911NF-11-1-0473)National Science Foundation (U.S.) (NSF DBI-1053486)Howard Hughes Medical Institute (Early Career Scientist

Observation of Small Cluster Formation in Concentrated Monoclonal Antibody Solutions and Its Implications to Solution Viscosity

AbstractMonoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions

IRAC Full-Scale Flight Testbed Capabilities

Overview: Provide validation of adaptive control law concepts through full scale flight evaluation in a representative avionics architecture. Develop an understanding of aircraft dynamics of current vehicles in damaged and upset conditions Real-world conditions include: a) Turbulence, sensor noise, feedback biases; and b) Coupling between pilot and adaptive system. Simulated damage includes 1) "B" matrix (surface) failures; and 2) "A" matrix failures. Evaluate robustness of control systems to anticipated and unanticipated failures