Pterodactyl: Thermal Protection System for Integrated Control Design of a Mechanically Deployed Entry Vehicle

The need for precision landing of high mass payloads on Mars and the return of sensitive samples from other planetary bodies to specific locations on Earth is driving the development of an innovative NASA technology referred to as the Deployable Entry Vehicle (DEV). A DEV has the potential to deliver an equivalent science payload with a stowed diameter 3 to 4 times smaller than a traditional rigid capsule configuration. However, the DEV design does not easily lend itself to traditional methods of directional control. The NASA Space Technology Mission Directorate (STMD)s Pterodactyl project is currently investigating the effectiveness of three different Guidance and Control (G&C) systems actuated flaps, Center of Gravity (CG) or mass movement, and Reaction Control System (RCS) for use with a DEV using the Adaptable, Deployable, Entry, and Placement Technology (ADEPT) design. This paper details the Thermal Protection System (TPS) design and associated mass estimation efforts for each of the G&C systems. TPS is needed for the nose cap of the DEV and the flaps of the actuated flap control system. The development of a TPS selection, sizing, and mass estimation method designed to deal with the varying requirements for the G&C options throughout the trajectory is presented. The paper discusses the methods used to i) obtain heating environments throughout the trajectory with respect to the chosen control system and resulting geometry; ii) determine a suitable TPS material; iii) produce TPS thickness estimations; and, iv) determine the final TPS mass estimation based on TPS thickness, vehicle control system, vehicle structure, and vehicle payload

A direct-to-drive neural data acquisition system

Driven by the increasing channel count of neural probes, there is much effort being directed to creating increasingly scalable electrophysiology data acquisition (DAQ) systems. However, all such systems still rely on personal computers for data storage, and thus are limited by the bandwidth and cost of the computers, especially as the scale of recording increases. Here we present a novel architecture in which a digital processor receives data from an analog-to-digital converter, and writes that data directly to hard drives, without the need for a personal computer to serve as an intermediary in the DAQ process. This minimalist architecture may support exceptionally high data throughput, without incurring costs to support unnecessary hardware and overhead associated with personal computers, thus facilitating scaling of electrophysiological recording in the future.National Institutes of Health (U.S.) (Grant 1DP1NS087724)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 2R44NS070453)National Institutes of Health (U.S.) (Grant R43MH101943)New York Stem Cell FoundationPaul Allen FoundationMassachusetts Institute of Technology. Media LaboratoryGoogle (Firm)United States. Defense Advanced Research Projects Agency (HR0011-14-2-0004)Hertz Foundation (Myhrvold Family Fellowship

A VLT spectroscopic survey of RX J0152.7-1357, a forming cluster of galaxies at z=0.837

We present the results of an extensive spectroscopic survey of RX J0152.7-1357, one of the most massive distant clusters of galaxies known. Multi-object spectroscopy, carried out with FORS1 and FORS2 on the ESO Very Large Telescope (VLT), has allowed us to measure more than 200 redshifts in the cluster field and to confirm 102 galaxies as cluster members. The mean redshift of the cluster is $z=0.837 \pm 0.001$ and we estimate the velocity dispersion of the overall cluster galaxy distribution to be $\sim 1600 \mathrm{km \ s^{-1}}$. The distribution of cluster members is clearly irregular, with two main clumps that follow the X-ray cluster emission mapped by Chandra. A third clump of galaxies to the east of the central structure and at the cluster redshift has also been identified. The two main clumps have velocity dispersions of$\sim919$and$\sim737 \mathrm{km s^{-1}}$respectively, and the peculiar velocity of the two clumps suggests that they will merge into a single more massive cluster. A segregation in the star formation activity of the member galaxies is observed. All star forming galaxies are located outside the high-density peaks, which are populated only by passive galaxies. A population of red galaxies (belonging to the cluster red sequence) with clear post-starburst spectral features and [OII] ($\lambda$3727) emission lines is observed in the outskirts of the cluster. Two AGNs, which were previously confused with the diffuse X-ray emission from the intracluster medium in ROSAT and BeppoSAX observations, are found to be cluster members.Comment: 16 pages. 13 figures. Accepted for publication in Astronomy & Astrophysics. Tables 4 and 5 available in printed version. Corrected typos and missing reference

The Naturalistic Flight Deck System: An Integrated System Concept for Improved Single-Pilot Operations

This paper reviews current and emerging operational experiences, technologies, and human-machine interaction theories to develop an integrated flight system concept designed to increase the safety, reliability, and performance of single-pilot operations in an increasingly accommodating but stringent national airspace system. This concept, know as the Naturalistic Flight Deck (NFD), uses a form of human-centered automation known as complementary-automation (or complemation) to structure the relationship between the human operator and the aircraft as independent, collaborative agents having complimentary capabilities. The human provides commonsense knowledge, general intelligence, and creative thinking, while the machine contributes specialized intelligence and control, extreme vigilance, resistance to fatigue, and encyclopedic memory. To support the development of the NFD, an initial Concept of Operations has been created and selected normal and non-normal scenarios are presented in this document

Is Chytridiomycosis an Emerging Infectious Disease in Asia?

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world

The Sloan Digital Sky Survey: Technical Summary

The Sloan Digital Sky Survey (SDSS) will provide the data to support detailed investigations of the distribution of luminous and non- luminous matter in the Universe: a photometrically and astrometrically calibrated digital imaging survey of pi steradians above about Galactic latitude 30 degrees in five broad optical bands to a depth of g' about 23 magnitudes, and a spectroscopic survey of the approximately one million brightest galaxies and 10^5 brightest quasars found in the photometric object catalog produced by the imaging survey. This paper summarizes the observational parameters and data products of the SDSS, and serves as an introduction to extensive technical on-line documentation.Comment: 9 pages, 7 figures, AAS Latex. To appear in AJ, Sept 200

Gallium incorporation into phosphate based glasses: bulk and thin film properties

The osteogenic ions Ca2+, P5+, Mg2+, and antimicrobial ion Ga3+ were homogenously dispersed into a 1.45 mum thick phosphate glass coating by plasma assisted sputtering onto CP grade titanium. The objective was to deliver therapeutic ions in orthopedic/dental implants such as hip prosthesis or dental screws. The hardness 4.7 GPa and elastic modulus 69.7 GPa, of the coating were comparable to plasma sprayed hydroxyapatite/dental enamel, whilst superseding femoral cortical bone. To investigate the manufacturing challenge of translation from a target to vapour condensed coating, structural/compositional properties of the target (P51MQ) were compared to the coating (P40PVD) and a melt-quenched equivalent (P40MQ). Following condensation from P51MQ to P40PVD, P2O5 content reduced from 48.9 to 40.5 mol%. This depolymerisation and reduction in the P-O-P bridging oxygen content as determined by 31P-NMR, FTIR and Raman spectroscopy techniques was attributed to a decrease in the P2O5 network former and increases in alkali/alkali-earth cations. P40PVD appeared denser (3.47 vs. 2.70 g cm-3) and more polymerised than it’s compositionally equivalent P40MQ, showing that structure/ mechanical properties were affected by manufacturing route

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570