Developing Open Source Software using Version Control Systems: An Introduction to the Git Language for Documenting Your Computational Research

Version control systems track the history of code as it is committed (saved) by any number of developers. Have you made a coding error and cannot debug it? Version control systems allow for resetting code back to when it worked, and show what code has changed since previous commits. The contents of this lecture provide an introduction to the git version control language, GitHub for cloud hosting open source code repositories, and tutorials that demonstrate common and useful git and GitHub practices. This lecture is intended to be coupled with a discussion on creating reproducible computational research.The zipped folder contains: 1. pre-meeting software installation instructions, 2. references for discussion on reproducibility, coding best practices, and legal issues, and 3. slideshow with tutorial. Commands needed for the tutorial are in the slide notes. Links to additional video tutorials are provided in a slide. Combined, the presentation + reproducibility discussion + tutorial are designed to take about 50 minutes to complete. If used in a course, the tutorial information on the hidden slides could be used as part of a student assignment

Completion of the Long Duration Wear Test of the NASA HERMeS Hall Thruster

The NASA Hall Effect Rocket with Magnetic Shielding (HERMeS) 12.5-kW Hall thruster has been the subject of extensive technology maturation by NASA GRC and JPL in preparation for development into a flight propulsion system. As part of this effort, a series of wear tests have been conducted to identify erosion phenomena and the accompanying failure modes as well as to validate service-life models for magnetically-shielded thrusters. This work presents a summary of the results obtained during the Long Duration Wear Test (LDWT), which was the third in this wear test series. The LDWT accumulated approximately 3,570 hours of operation and had the overall goal to identify and correct design or facility issues prior to the flight qualification campaign. Thruster performance, stability, and plume properties were invariant throughout the duration of the LDWT and consistent with measurements acquired during previous HERMeS performance and wear characterizations. Average erosion rates of a carbon-carbon composite pole cover were found to match those measured with graphite to within the empirical uncertainty while the previously observed time-dependence of pole cover erosion rates was linked to changes in pole cover roughness. Azimuthal variations in keeper wear rate were observed including deposition on one of the azimuthal-facing sides of the keeper mask. This strongly suggests the presence of an azimuthal component in the process driving keeper erosion

Methodological Differences Cannot Explain Associations Between Health, Anthropometrics, and Excess Resting Metabolic Rate

We appreciate Ocobock\u27s interest in methodological rigor. We largely agree with her commentary, which suggests that departures from standard protocols might have contributed to the high resting metabolic rate (RMR) measured for Tsimane. Indeed, our paper acknowledges many of the key departures from gold-standard indirect calorimetry methods of RMR assessment and attempts to adjust for several of these (Gurven et al., 2016). Bringing standard clinical methods into remote field settings often involves certain compromises, especially in our case, where RMR measurement was just one component of a large-scale health and aging project (Gurven et al., 2017). RMR data collection was from 2012 to 2014, and where we to measure RMR again for focused follow up, we would consider new available technologies, improve our protocol to the extent possible, and compare against our published estimates

Tracking the impacts of precipitation phase changes through the hydrologic cycle in snowy regions: From precipitation to reservoir storage

Cool season precipitation plays a critical role in regional water resource management in the western United States. Throughout the twenty-first century, regional precipitation will be impacted by rising temperatures and changing circulation patterns. Changes to precipitation magnitude remain challenging to project; however, precipitation phase is largely dependent on temperature, and temperature predictions from global climate models are generally in agreement. To understand the implications of this dependence, we investigate projected patterns in changing precipitation phase for mountain areas of the western United States over the twenty-first century and how shifts from snow to rain may impact runoff. We downscale two bias-corrected global climate models for historical and end-century decades with the Weather Research and Forecasting (WRF) regional climate model to estimate precipitation phase and spatial patterns at high spatial resolution (9 km). For future decades, we use the RCP 8.5 scenario, which may be considered a very high baseline emissions scenario to quantify snow season differences over major mountain chains in the western U.S. Under this scenario, the average annual snowfall fraction over the Sierra Nevada decreases by >45% by the end of the century. In contrast, for the colder Rocky Mountains, the snowfall fraction decreases by 29%. Streamflow peaks in basins draining the Sierra Nevada are projected to arrive nearly a month earlier by the end of the century. By coupling WRF with a water resources model, we estimate that California reservoirs will shift towards earlier maximum storage by 1–2 months, suggesting that water management strategies will need to adapt to changes in streamflow magnitude and timing

Visible Thermal Emission from Sub-Band-Gap Laser Excited Cerium Dioxide Particles

Cerium dioxide particles excited in air with sub-band-gap radiation emit very broad radiation in the visible spectrum above a threshold intensity that decreases with increasing ambient temperature. Concomitant with this emission is the near disappearance of the Stokes and anti-Stokes Raman scattering peaks. Both phenomena are reversible in air up to just above threshold, and are seen for nanoparticles and several-micron-diameter particles with particle diameter comparable to or smaller than the laser focus. Temperature estimates using the Stokes/anti-Stokes scattering intensity ratio suggest there is laser heating due to small intragap absorption and possible nonlinear processes, given the very slow thermal conduction. The broad emission in this loose powder may well be due to thermal emission, on the basis of spectral fitting of the high-energy part of the spectrum to a blackbody radiator at ϳ1200-1400°C, although luminescence from a new phase is a possibility. The sudden decrease in Raman scattering and increase in emission in air are consistent with a transition to a new, possibly luminescent, phase, as is the continued disappearance of the Raman peaks in forming gas when the laser power is reduced below the upstroke threshold. Oxygen point defects and their complexes may play an important role in many of these processes

Distinct inactive conformations of the dopamine D2 and D3 receptors correspond to different extents of inverse agonism

By analyzing and simulating inactive conformations of the highly-homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/risperidone structure. In addition, risperidone occupies a sub-pocket near the Na+ binding site, whereas eticlopride does not. Based on these findings and our experimental results, we propose that the divergent receptor conformations stabilized by Na+-sensitive eticlopride and Na+-insensitive risperidone correspond to different degrees of inverse agonism. Moreover, our simulations reveal that the extracellular loops are highly dynamic, with spontaneous transitions of extracellular loop 2 from the helical conformation in the D2R/risperidone structure to an extended conformation similar to that in the D3R/eticlopride structure. Our results reveal previously unappreciated diversity and dynamics in the inactive conformations of D2R. These findings are critical for rational drug discovery, as limiting a virtual screen to a single conformation will miss relevant ligands

In-Situ Diagnostic for Assessing Hall Thruster Wear

The design of a new diagnostic to measure the net erosion of Hall thruster surfaces is presented. This diagnostic consists of a pair of optical non-contact profilometer pens mounted to a set of motion stages, which can interrogate the surface features of multiple components of interest including the hollow cathode assembly, magnet front pole covers, and discharge channel. By comparing scans of these surfaces to reference features, estimates of the component erosion rates can be acquired throughout long-duration lifetime tests without venting and removing the thruster from the vacuum facility for external profilometry. This work presents a detailed overview of the diagnostic design including the precision positioning system. In addition, preliminary data are shown which verify diagnostic operation and establish a baseline that will be used to track the erosion of the Hall Effect Rocket with Magnetic Shielding (HERMeS) Technology Demonstration Unit 3 (TDU-3) during an ongoing long-duration wear test

A genomic and evolutionary approach reveals non-genetic drug resistance in malaria

Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0511-2) contains supplementary material, which is available to authorized users

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the side effects elicited by antagonists. The receptor-ligand interactions that determine the intrinsic efficacy of such drugs, however, are poorly understood. Aripiprazole has an extended structure comprising a phenylpiperazine primary pharmacophore and a 1,2,3,4-tetrahydroquinolin-2-one secondary pharmacophore. We combined site-directed mutagenesis, analytical pharmacology, ligand fragments and molecular dynamics simulations to identify the D2R-aripiprazole interactions that contribute to affinity and efficacy. We reveal that an interaction between the secondary pharmacophore of aripiprazole and a secondary binding pocket defined by residues at the extracellular portions of transmembrane segments 1, 2 and 7 determine the intrinsic efficacy of aripiprazole. Our findings reveal a hitherto unappreciated mechanism through which to fine-tune the intrinsic efficacy of D2R agonists