NASA Oxygen and Water Production Architectures for Early Reusable Lander

The presentation covers two recent studies Lunar In Situ Resource Utilization (ISRU) systems to produce propellant for an early reusable lander architecture. The first study examines the hardware, power, and operations required to produce 10 metric tons of oxygen per year near the lunar south pole using the Carbothermal Reduction process. The second study examines the hardware, power, and operations to mine and process 15 metric tons of water from a permanently shadowed crater near Shackleton crater

HIV-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind CD4 with High Affinity, while the CD4 Binding Site on Non-macrophage-tropic, T-Tropic R5 Envelopes Is Occluded

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of the Env trimer for CD4 or is mediated by postbinding structural rearrangements in the trimer that enhance the exposure of the coreceptor binding site and facilitate events leading to fusion and virus entry. In this study, we investigated CD4 binding to mac-tropic and non-mac-tropic Env trimers and showed that CD4-IgG binds efficiently to mac-tropic R5 Env trimers, while binding to non-mac-tropic trimers was undetectable. Our data indicated that the CD4 binding site (CD4bs) is highly occluded on Env trimers of non-mac-tropic R5 viruses. Such viruses may therefore infect T cells via viral synapses where Env and CD4 become highly concentrated. This environment will enable high-avidity interactions that overcome extremely low Env-CD4 affinities. IMPORTANCE HIV R5 variants bind to CD4 and CCR5 receptors on T cells and macrophages to initiate infection. Transmitted HIV variants infect T cells but not macrophages, and these viral strains persist in immune tissue even in late disease. Here we show that the binding site for CD4 present on HIV\u27s envelope protein is occluded on viruses replicating in immune tissue. This occlusion likely prevents antibody binding to this site and neutralization of the virus, but it makes it difficult for virus-CD4 interactions to occur. Such viruses probably pass from T cell to T cell via cell contacts where CD4 is highly concentrated and allows infection via inefficient envelope-CD4 binding. Our data are highly relevant for vaccines that aim to induce antibodies targeting the CD4 binding site on the envelope protein

Efficiency of bridging-sheet recruitment explains HIV-1 R5 envelope glycoprotein sensitivity to soluble CD4 and macrophage tropism

HIV-1 R5 viruses vary extensively in their capacity to infect macrophages. R5 viruses that confer efficient infection of macrophages are able to exploit low levels of CD4 for infection and predominate in brain tissue, where macrophages are a major target for infection. HIV-1 R5 founder viruses that are transmitted were reported to be non-macrophage-tropic. Here, we investigated the sensitivities of macrophage-tropic and non-macrophage-tropic R5 envelopes to neutralizing antibodies. We observed striking differences in the sensitivities of Env(+) pseudovirions to soluble CD4 (sCD4) and to neutralizing monoclonal antibodies (MAbs) that target the CD4 binding site. Macrophage-tropic R5 Envs were sensitive to sCD4, while non-macrophage-tropic Envs were significantly more resistant. In contrast, all Envs were sensitive to VRC01 regardless of tropism, while MAb b12 conferred an intermediate neutralization pattern where all the macrophage-tropic and about half of the non-macrophage-tropic Envs were sensitive. CD4, b12, and VRC01 share binding specificities on the outer domain of gp120. However, these antibodies differ in their ability to induce conformational changes on the trimeric envelope and in specificity for residues on the V1V2 loop stem and beta20-21 junction that are targets for CD4 in recruiting the bridging sheet. These distinct specificities of CD4, b12, and VRC01 likely explain the observed differences in Env sensitivity to inhibition by these reagents and provide an insight into the envelope mechanisms that control macrophage tropism. We present a model where the efficiency of bridging-sheet recruitment by CD4 is a major determinant of HIV-1 R5 envelope sensitivity to soluble CD4 and macrophage tropism

Volatiles Loss from Water Bearing Regolith Simulant at Lunar Environments

Permanently shadowed craters at the lunar poles contain water, ~5 wt% according to LCROSS. Interest in water for ISRU applications. Desire to 'ground truth' water using surface prospecting; e.g. Resource Prospector (RP) & RESOLVE. How to access subsurface water resources and accurately measure quantity; Excavation operations and exposure to lunar environment may affect the results A series a ground based dirty thermal vacuum tests are being conducted to better understand the subsurface sampling operations: Sample removal and transfer, Volatiles loss during sampling operations, Concept of operations, Instrumentation. This presentation covers: The capabilities of the VF-13 Thermal Vacuum Chamber (Tvac). The Resource Prospector TVAC hardware. The summary and results of 5 years of RP volatiles tests; 43 viable sample

Rotation Curve Fitting Model

One key piece of evidence for dark matter is the flat rotation curve problem: the disagreement between measured galactic rotation curves and their luminous mass. A novel solution to this problem is presented here. A model of relativistic frame effects on Doppler shifts due to the slightly curved frames of an emitting galaxy and the Milky Way is derived. This model predicts observed Doppler shifted spectra (in excess of the luminous mass) based only on the observed luminous matter profile and one free model parameter. Fits to the 175 galaxies reported in the SPARC database of galactic rotation profiles and accurate photometry measurements are compared between this novel model and dark matter and MOND (RAR) models. We find on the SPARC sample of 175 galaxies; that MOND-RAR has an average reduced chisquare of $\chi^2_r = 4.22$ for 175 galaxies fitted, the isothermal dark matter model has $\chi^2_r = 1.90$ for 165 galaxies fitted, and the new model we present has $\chi^2_r = 2.39$ for 172 galaxies fitted. Implications of this model are discussed.Comment: 27 pages, 9 figure

Probing the earliest phases in the formation of massive galaxies with simulated HST+JWST imaging data from Illustris

We use the Illustris-1 simulation to explore the capabilities of the $\textit{Hubble}$ and $\textit{James Webb Space Telescope}$ data to analyze the stellar populations in high-redshift galaxies, taking advantage of the combined depth, spatial resolution, and wavelength coverage. For that purpose, we use simulated broad-band ACS, WFC3 and NIRCam data and 2-dimensional stellar population synthesis (2D-SPS) to derive the integrated star formation history (SFH) of massive (M$_{\ast}>10^{10}\,$M$_{\odot}$) simulated galaxies at $110^{11}\,$M$_{\odot}$ galaxy. In particular, we explore the potential of HST and JWST datasets reaching a depth similar to those of the CANDELS and ongoing CEERS observations, respectively, and concentrate on determining the capabilities of this dataset for characterizing the first episodes in the SFH of local M$_{\ast}>10^{11}\,$M$_{\odot}$ galaxies by studying their progenitors at $z>1$. The 2D-SPS method presented in this paper has been calibrated to robustly recover the cosmic times when the first star formation episodes occurred in massive galaxies, i.e., the first stages in their integrated SFHs. In particular, we discuss the times when the first 1% to 50% of their total stellar mass formed in the simulation. We demonstrate that we can recover these ages with typical median systematic offset of less than 5% and scatter around 20%-30%. According to our measurements on Illustris data, we are able to recover that local M$_{\ast}>10^{11}\,$M$_{\odot}$ galaxies would have started their formation by $z=16$, forming the first 5% of their stellar mass present at $z \sim 1$ by $z=4.5$, 10% by $z=3.7$, and 25% by $z=2.7$.Comment: 28 pages, 13 figures, 4 tables. ApJ in press. Summary of changes from original submission: the major change is that we now include in Sec. 6 the comparison of the results obtained for our sample of massive 1 < z < 4 progenitors with those obtained by considering all massive galaxies at 1 < z < 4 in the simulated images. Several figures and sections have been update

Processing speed and memory test performance are associated with different brain region volumes in Veterans and others with progressive multiple sclerosis

BackgroundCognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates.ObjectivesThis study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes.DesignThe study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028).MethodsCognitive batteries were conducted by trained research personnel. MRIs were processed at a central processing site for maximum harmonization. Semi-partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts.ResultsOf the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of 22.4 (sd 11.3) years, and had a median Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0–6.0, moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p &lt; 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated with mean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p &lt; 0.01, respectively). Correlation patterns were similar in subgroup analyses.ConclusionBrain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressive MS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations

The Carnegie-Irvine Galaxy Survey. I. Overview and Atlas of Optical Images

The Carnegie-Irvine Galaxy Survey (CGS) is a long-term program to investigate the photometric and spectroscopic properties of a statistically complete sample of 605 bright (B_T < 12.9 mag), southern (Dec. < 0) galaxies using the facilities at Las Campanas Observatory. This paper, the first in a series, outlines the scientific motivation of CGS, defines the sample, and describes the technical aspects of the optical broadband (BVRI) imaging component of the survey, including details of the observing program, data reduction procedures, and calibration strategy. The overall quality of the images is quite high, in terms of resolution (median seeing 1"), field of view (8.9' X 8.9'), and depth (median limiting surface brightness 27.5, 26.9, 26.4, and 25.3 mag/arcsec2 in the B, V, R, and I bands, respectively). We prepare a digital image atlas showing several different renditions of the data, including three-color composites, star-cleaned images, stacked images to enhance faint features, structure maps to highlight small-scale features, and color index maps suitable for studying the spatial variation of stellar content and dust. In anticipation of upcoming science analyses, we tabulate an extensive set of global properties for the galaxy sample. These include optical isophotal and photometric parameters derived from CGS itself, as well as published information on multiwavelength (ultraviolet, U-band, near-infrared, far-infrared) photometry, internal kinematics (central stellar velocity dispersions, disk rotational velocities), environment (distance to nearest neighbor, tidal parameter, group or cluster membership), and H I content. The digital images and science-level data products will be made publicly accessible to the community.Comment: To appear in ApJS. This is the companion paper to Li et al. (2011). Online materials and other information available in the CGS website http://cgs.obs.carnegiescience.ed

Mutational heterogeneity in cancer and the search for new cancer genes

Major international projects are now underway aimed at creating a comprehensive catalog of all genes responsible for the initiation and progression of cancer. These studies involve sequencing of matched tumor–normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here, we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false positive findings that overshadow true driver events. Here, we show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumor-normal pairs and discover extraordinary variation in (i) mutation frequency and spectrum within cancer types, which shed light on mutational processes and disease etiology, and (ii) mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and allow true cancer genes to rise to attention

The role of pulmonary arterial stiffness in COPD

AbstractCOPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests.The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs