Selection of systems to perform extravehicular activities, man and manipulator. Volume 1 - Performance Effectiveness Evaluation Scheme /PEEVS/. Part A - Instructions

Performance effectiveness evaluation scheme for EVA systems selection - instruction

Selection of systems to perform extravehicular activities, man and manipulator. Volume 2 - Final report

Technologies for EVA and remote manipulation systems - handbook for systems designer

DNA nanotweezers studied with a coarse-grained model of DNA

We introduce a coarse-grained rigid nucleotide model of DNA that reproduces the basic thermodynamics of short strands: duplex hybridization, single-stranded stacking and hairpin formation, and also captures the essential structural properties of DNA: the helical pitch, persistence length and torsional stiffness of double-stranded molecules, as well as the comparative flexibility of unstacked single strands. We apply the model to calculate the detailed free-energy landscape of one full cycle of DNA 'tweezers', a simple machine driven by hybridization and strand displacement.Comment: 4 pages, 5 figure

Empirical corrections to the Amber RNA force field with Target Metadynamics

The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the \u3b1 and \u3b6 backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement

Helix-dependent Spin Filtering through the DNA Duplex

Recent work suggests that electrons can travel through DNA and other chiral molecules in a spin-selective manner, but little is known about the origin of this spin selectivity. Here we describe experiments on magnetized DNA-modified electrodes to explore spin-selective electron transport through hydrated duplex DNA. Our results show that the two spins migrate through duplex DNA with different yield, and that spin selectivity requires charge transport through the DNA duplex. Significantly, shifting the same duplex DNA between right-handed B- and left-handed Z-forms leads to a diode-like switch in spin-selectivity; which spin moves more efficiently through the duplex depends upon the DNA helicity. With DNA, the supramolecular organization of chiral moieties, rather than the chirality of the individual monomers, determines the selectivity in spin, and thus a conformational change can switch the spin selectivity

Tropical sea surface temperatures for the past four centuries reconstructed from coral archives

Most annually resolved climate reconstructions of the Common Era are based on terrestrial data, making it a challenge to independently assess how recent climate changes have affected the oceans. Here as part of the Past Global Changes Ocean2K project, we present four regionally calibrated and validated reconstructions of sea surface temperatures in the tropics, based on 57 published and publicly archived marine paleoclimate data sets derived exclusively from tropical coral archives. Validation exercises suggest that our reconstructions are interpretable for much of the past 400 years, depending on the availability of paleoclimate data within, and the reconstruction validation statistics for, each target region. Analysis of the trends in the data suggests that the Indian, western Pacific, and western Atlantic Ocean regions were cooling until modern warming began around the 1830s. The early 1800s were an exceptionally cool period in the Indo-Pacific region, likely due to multiple large tropical volcanic eruptions occurring in the early nineteenth century. Decadal-scale variability is a quasi-persistent feature of all basins. Twentieth century warming associated with greenhouse gas emissions is apparent in the Indian, West Pacific, and western Atlantic Oceans, but we find no evidence that either natural or anthropogenic forcings have altered El Ni ˜no–Southern Oscillation-related variance in tropical sea surface temperatures. Our marine-based regional paleoclimate reconstructions serve as benchmarks against which terrestrial reconstructions as well as climate model simulations can be compared and as a basis for studying the processes by which the tropical oceans mediate climate variability and change

Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition

Background Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. Case presentation We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab. Conclusion Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy

Quantitative Proteomic Approach Identifies Vpr Binding Protein as Novel Host Factor Supporting Influenza A Virus Infections in Human Cells

Influenza A virus infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. IAV have a large natural host reservoir in avian species. However, many avian IAV strains lack adaptation to other hosts and hardly propagate in humans. While seasonal or pandemic influenza A virus (IAV) strains replicate efficiently in permissive human cells, many avian IAV cause abortive non-productive infections in these hosts despite successful cell entry. However, the precise reasons for these differential outcomes are poorly defined. We hypothesized that the distinct course of an IAV infection with a given virus strain is determined by the differential interplay between specific host and viral factors. By using Spike-in SILAC mass spectrometry-based quantitative proteomics we characterized sets of cellular factors whose abundance is specifically up- or down-regulated in the course of permissive vs. non-permissive IAV infection, respectively. This approach allowed for the definition and quantitative comparison of about 3500 proteins in human lung epithelial cells in response to seasonal or low-pathogenic avian H3N2 IAV. Many identified proteins were similarly regulated by both virus strains, but also 16 candidates with distinct changes in permissive vs. non-permissive infection were found. RNAi-mediated knockdown of these differentially regulated host factors identified Vpr binding protein (VprBP) as pro-viral host factor since its down-regulation inhibited efficient propagation of seasonal IAV while over-expression increased viral replication of both seasonal and avian IAV. These results not only show that there are similar differences in the overall changes during permissive and non-permissive imfluenza virus infections, but also provide a basis to evaluate VprBP as novel anti-IAV drug target

Spatial and temporal robustness of Sr/Ca‐SST calibrations in Red Sea corals : evidence for influence of mean annual temperature on calibration slopes

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Paleoceanography and Paleoclimatology 33 (2018): 443-456, doi:10.1029/2017PA003276.Sr/Ca ratios recorded in the aragonite skeleton of massive coral colonies are commonly used to reconstruct seasonal‐ to centennial‐scale variability in sea surface temperature (SST). While the Sr/Ca paleothermometer is robust in individual colonies, Sr/Ca‐SST relationships between colonies vary, leading to questions regarding the utility of the proxy. We present biweekly‐resolution calibrations of Sr/Ca from five Porites spp. corals to satellite SST across 10° of latitude in the Red Sea to evaluate the Sr/Ca proxy across both spatial and temporal scales. SST is significantly correlated with coral Sr/Ca at each site, accounting for 69–84% of Sr/Ca variability (P ≪ 0.01). Intercolony variability in Sr/Ca‐SST sensitivities reveals a latitudinal trend, where calibration slopes become shallower with increasing mean annual temperature. Mean annual temperature is strongly correlated with the biweekly‐resolution calibration slopes across five Red Sea sites (r2 = 0.88, P = 0.05), while also correlating significantly to Sr/Ca‐SST slopes for 33 Porites corals from across the entire Indo‐Pacific region (r2 = 0.26, P < 0.01). Although interannual summer, winter, and mean annual calibrations for individual Red Sea colonies are inconsistently robust, combined multicoral calibrations are significant at summer (r2 = 0.53, P ≪ 0.01), winter (r2 = 0.62, P ≪ 0.01), and mean annual time scales (r2 = 0.79, P ≪ 0.01). Our multicoral, multisite study indicates that the Sr/Ca paleothermometer is accurate across both temporal and spatial scales in the Red Sea and also potentially explains for the first time variability in Sr/Ca‐SST calibration slopes across the Indo‐Pacific region. Our study provides strong evidence supporting the robustness of the coral Sr/Ca proxy for examining seasonal to multicentury variability in global climate phenomena.Singapore Ministry of Education; National Research Foundation Singapore Grant Number: NRFF‐2012‐03; U.S. National Science Foundation Grant Number: OCE‐1031288; King Abdullah University of Science and Technology Grant Numbers: USA 00002, KSA 0001

Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB).

Two interferences recently brought to the forefront as patient safety issues include hemolysis (hemoglobin) and biotin (vitamin B7). The International Federation for Clinical Chemistry Committee on Cardiac Biomarkers (IFCC-CB) obtained input from a majority of cTn and NP assay manufacturers to collate information related to high-sensitivity (hs)-cTnI, hs-cTnT, contemporary, and POC cTn assays, and NP assays interferences due to hemolysis and biotin. The information contained in these tables was designed as educational tools to aid laboratory professionals and clinicians in troubleshooting cardiac biomarker analytical results that are discordant with the clinical situation