Thermal protection system ablation sensor

An isotherm sensor tracks space vehicle temperatures by a thermal protection system (TPS) material during vehicle re-entry as a function of time, and surface recession through calibration, calculation, analysis and exposed surface modeling. Sensor design includes: two resistive conductors, wound around a tube, with a first end of each conductor connected to a constant current source, and second ends electrically insulated from each other by a selected material that becomes an electrically conductive char at higher temperatures to thereby complete an electrical circuit. The sensor conductors become shorter as ablation proceeds and reduced resistance in the completed electrical circuit (proportional to conductor length) is continually monitored, using measured end-to-end voltage change or current in the circuit. Thermocouple and/or piezoelectric measurements provide consistency checks on local temperatures

Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ

Background: Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining. Results: Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved convenient one-step knock-in of gene cassettes and floxed allele both in human cells and mouse zygotes. Conclusions: Our results provide a technical platform for high-throughput knock-in

Mars 2020 Entry, Descent and Landing Instrumentation 2 (MEDLI2)

The Mars Entry Descent and Landing Instrumentation 2 (MEDLI2) sensor suite will measure aerodynamic, aerothermodynamic, and TPS performance during the atmospheric entry, descent, and landing phases of the Mars 2020 mission. The key objectives are to reduce design margin and prediction uncertainties for the aerothermal environments and aerodynamic database. For MEDLI2, the sensors are installed on both the heatshield and backshell, and include 7 pressure transducers, 17 thermal plugs, and 3 heat flux sensors (including a radiometer). These sensors will expand the set of measurements collected by the highly successful MEDLI suite, collecting supersonic pressure measurements on the forebody, a pressure measurement on the aftbody, direct heat flux measurements on the aftbody, a radiative heating measurement on the aftbody, and multiple near-surface thermal measurements on the thermal protection system (TPS) materials on both the forebody and aftbody. To meet the science objectives, supersonic pressure transducers and heat flux sensors are currently being developed and their qualification and calibration plans are presented. Finally, the reconstruction targets for data accuracy are presented, along with the planned methodologies for achieving the targets

Transcription and Translation Products of the Cytolysin Gene psm-mec on the Mobile Genetic Element SCCmec Regulate Staphylococcus aureus Virulence

The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Layered heat flux gauges for aeroentry application

A layered heat flux gauge, which can withstand a high temperature environment for applications such as for use on thermal protection shields on aeroentry vehicles, is analyzed, designed, fabricated, and tested. The heat flux gauge consists of two resistance temperature detectors on the top and bottom faces of a thin ceramic substrate. The heat flux is calculated from temperature measurements of the two temperature detectors. An analytical model is used to simulate the gauge response. Several numerical methods to calculate the heat flux are investigated to improve the time response of the gauge. The error due to gauge intrusiveness and the validity of one-dimensional heat transfer within the gauge is studied by solving a steady state two-dimensional composite problem using a semi-analytical approach. Gauge fabrication techniques and measurement devices are discussed. Testing apparatus, including a "close-to-entry" condition apparatus using an arcjet at low pressure and a conduction calibration furnace, are explained. Experimental data showing qualitative gauge response is presented

Electrochemical Dy-alloying behaviors of Ni-based alloys in molten LiF–CaF₂–DyF₃ and LiCl–KCl–DyCl₃: Effects of temperature and electrolysis potential

The effects of temperature and electrolysis potential on the alloying rate, structure, and mechanical strength for the Dy-alloyed Hastelloy C-276 samples, where Hastelloy C-276 is a Ni-based alloy containing Cr and Mo, were investigated in a molten LiF–CaF₂–DyF₃ (0.30 or 0.50 mol%) system at 1123–1323 K and a molten LiCl–KCl–DyCl₃ (0.50 mol%) system at 873 K. The microstructure was studied by electron microscopy and energy-dispersive X-ray spectrometry analyses, and the mechanical strength of the formed Dy-alloys was evaluated using punch tests. The alloying rate was influenced by the electrolysis potential and significantly by the temperature. Phase separation into DyNi₂ and Cr–Mo was observed, and a layered structure perpendicular to the depth direction was formed. The pitch of the layered structure was found to depend on the electrolysis potential, suggesting that the diffusion rate of Cr and Mo determined the structure. The Dy-alloyed samples electrolyzed at a more negative potential in the LiCl–KCl–DyCl₃ melt exhibited a higher mechanical strength. The Dy-alloyed samples obtained in the LiF–CaF₂–DyF₃ melt at 1223 K and 1323 K exhibited a low mechanical strength owing to the large grain size of the agglomerated Cr–Mo alloy phase

Two mouse models carrying truncating mutations in Magel2 show distinct phenotypes.

Schaaf-Yang syndrome (SYS) is a neurodevelopmental disorder caused by truncating variants in the paternal allele of MAGEL2, located in the Prader-Willi critical region, 15q11-q13. Although the phenotypes of SYS overlap those of Prader-Willi syndrome (PWS), including neonatal hypotonia, feeding problems, and developmental delay/intellectual disability, SYS patients show autism spectrum disorder and joint contractures, which are atypical phenotypes for PWS. Therefore, we hypothesized that the truncated Magel2 protein could potentially produce gain-of-function toxic effects. To test the hypothesis, we generated two engineered mouse models; one, an overexpression model that expressed the N-terminal region of Magel2 that was FLAG tagged with a strong ubiquitous promoter, and another, a genome-edited model that carried a truncating variant in Magel2 generated using the CRISPR/Cas9 system. In the overexpression model, all transgenic mice died in the fetal or neonatal period indicating embryonic or neonatal lethality of the transgene. Therefore, overexpression of the truncated Magel2 could show toxic effects. In the genome-edited model, we generated a mouse model carrying a frameshift variant (c.1690_1924del; p(Glu564Serfs*130)) in Magel2. Model mice carrying the frameshift variant in the paternal or maternal allele of Magel2 were termed Magel2P:fs and Magel2M:fs, respectively. The imprinted expression and spatial distribution of truncating Magel2 transcripts in the brain were maintained. Although neonatal Magel2P:fs mice were lighter than wildtype littermates, Magel2P:fs males and females weighed the same as their wildtype littermates by eight and four weeks of age, respectively. Collectively, the overexpression mouse model may recapitulate fetal or neonatal death, which are the severest phenotypes for SYS. In contrast, the genome-edited mouse model maintains genomic imprinting and distribution of truncated Magel2 transcripts in the brain, but only partially recapitulates SYS phenotypes. Therefore, our results imply that simple gain-of-function toxic effects may not explain the patho-mechanism of SYS, but rather suggest a range of effects due to Magel2 variants as in human SYS patients