Molecular dynamics simulations of apo and holo forms of fatty acid binding protein 5 and cellular retinoic acid binding protein II reveal highly mobile protein, retinoic acid ligand, and water molecules

Structural and dynamic properties from a series of 300 ns molecular dynamics, MD, simulations of two intracellular lipid binding proteins, iLBPs, (Fatty Acid Binding Protein 5, FABP5, and Cellular Retinoic Acid Binding Protein II, CRABP-II) in both the apo form and when bound with retinoic acid reveal a high degree of protein and ligand flexibility. The ratio of FABP5 to CRABP-II in a cell may determine whether it undergoes natural apoptosis or unrestricted cell growth in the presence of retinoic acid. As a result, FABP5 is a promising target for cancer therapy. The MD simulations presented here reveal distinct differences in the two proteins and provide insight into the bindingmechanism. CRABP-II is a much larger, more flexible protein that closes upon ligand binding, where FABP5 transitions to an open state in the holo form. The traditional understanding obtained from crystal structures of the gap between two β-sheets of the β-barrel common to iLBPs and the α-helix cap that forms the portal to the binding pocket is insufficient for describing protein conformation (open vs. closed) or ligand entry and exit. When the high degree of mobility between multiple conformations of both the ligand and protein are examined via MD simulation, a new mode of ligand motion that improves understanding of binding dynamics is revealed

Power, Avionics and Software Communication Network Architecture

This document describes the communication architecture for the Power, Avionics and Software (PAS) 2.0 subsystem for the Advanced Extravehicular Mobile Unit (AEMU). The following systems are described in detail: Caution Warn- ing and Control System, Informatics, Storage, Video, Audio, Communication, and Monitoring Test and Validation. This document also provides some background as well as the purpose and goals of the PAS project at Glenn Research Center (GRC)

A Communication Architecture for an Advanced Extravehicular Mobile Unit

This document describes the communication architecture for the Power, Avionics and Software (PAS) 1.0 subsystem for the Advanced Extravehicular Mobility Unit (AEMU). The following systems are described in detail: Caution Warning and Control System, Informatics, Storage, Video, Audio, Communication, and Monitoring Test and Validation. This document also provides some background as well as the purpose and goals of the PAS subsystem being developed at Glenn Research Center (GRC)

Power, Avionics and Software - Phase 1.0:

This report describes Power, Avionics and Software (PAS) 1.0 subsystem integration testing and test results that occurred in August and September of 2013. This report covers the capabilities of each PAS assembly to meet integration test objectives for non-safety critical, non-flight, non-human-rated hardware and software development. This test report is the outcome of the first integration of the PAS subsystem and is meant to provide data for subsequent designs, development and testing of the future PAS subsystems. The two main objectives were to assess the ability of the PAS assemblies to exchange messages and to perform audio testing of both inbound and outbound channels. This report describes each test performed, defines the test, the data, and provides conclusions and recommendations

802.16e System Profile for NASA Extra-Vehicular Activities

This report identifies an 802.16e system profile that is applicable to a lunar surface wireless network, and specifically for meeting extra-vehicular activity (EVA) data flow requirements. EVA suit communication needs are addressed. Design-driving operational scenarios are considered. These scenarios are then used to identify a configuration of the 802.16e system (system profile) that meets EVA requirements, but also aim to make the radio realizable within EVA constraints. Limitations of this system configuration are highlighted. An overview and development status is presented by Toyon Research Corporation concerning the development of an 802.16e compatible modem under NASA s Small Business Innovative Research (SBIR) Program. This modem is based on the recommended system profile developed as part of this report. Last, a path forward is outlined that presents an evolvable solution for the EVA radio system and lunar surface radio networks. This solution is based on a custom link layer, and 802.16e compliant physical layer compliant to the identified system profile, and a later progression to a fully interoperable 802.16e system

Markers of sulfadoxine-pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample. Conclusions The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]