Activation of the E1 Ultra High Pressure Propulsion Test Facility at Stennis Space Center

After a decade of construction and a year of activation the El Ultra High Pressure Propulsion Test Facility at NASA's Stennis Space Center is fully operational. The El UHP Propulsion Test Facility is a multi-cell, multi-purpose component and engine test facility . The facility is capable of delivering cryogenic propellants at low, high, and ultra high pressures with flow rates ranging from a few pounds per second up to two thousand pounds per second. Facility activation is defined as a series of tasks required to transition between completion of construction and facility operational readiness. Activating the El UHP Propulsion Test Facility involved independent system checkouts, propellant system leak checks, fluid and gas sampling, gaseous system blow downs, pressurization and vent system checkouts, valve stability testing, valve tuning cryogenic cold flows, and functional readiness tests

Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing

Ultra-deep targeted sequencing (UDT-Seq) can identify subclonal somatic mutations in tumor samples. Early assays' limited breadth and depth restrict their clinical utility. Here, we target 71 kb of mutational hotspots in 42 cancer genes. We present novel methods enhancing both laboratory workflow and mutation detection. We evaluate UDT-Seq true sensitivity and specificity (> 94% and > 99%, respectively) for low prevalence mutations in a mixing experiment and demonstrate its utility using six tumor samples. With an improved performance when run on the Illumina Miseq, the UDT-Seq assay is well suited for clinical applications to guide therapy and study clonal selection in heterogeneous samples

Development of a small molecule that corrects misfolding and increases secretion of Z α1 -antitrypsin.

Severe α1 -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α1 -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α1 -antitrypsin. The lead compound blocks Z α1 -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α1 -antitrypsin threefold in an iPSC model of disease. Crystallographic and biophysical analyses demonstrate that GSK716 and related molecules bind to a cryptic binding pocket, negate the local effects of the Z mutation and stabilise the bound state against progression along the polymerisation pathway. Oral dosing of transgenic mice at 100 mg/kg three times a day for 20 days increased the secretion of Z α1 -antitrypsin into the plasma by sevenfold. There was no observable clearance of hepatic inclusions with respect to controls over the same time period. This study provides proof of principle that "mutation ameliorating" small molecules can block the aberrant polymerisation that underlies Z α1 -antitrypsin deficiency

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Resurgence of a Nation’s Radiation Science Driven by Its Nuclear Industry Needs

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-26, pub-electronic 2021-11-23Publication status: PublishedThis article describes the radiation facilities and associated sample preparation, management, and analysis equipment currently in place at the Dalton Cumbrian Facility, a facility which opened in 2011 to support the UK’s nuclear industry. Examples of measurements performed using these facilities are presented to illustrate their versatility and the breadth of research they make possible. Results are presented from research which furthers our understanding of radiation damage to polymeric materials, radiolytic yield of gaseous products in situations relevant to nuclear materials, radiation chemistry in light water reactor cooling systems, material chemistry relevant to immobilization of nuclear waste, and radiation-induced corrosion of fuel cladding elements. Applications of radiation chemistry relevant to health care are also described. Research concerning the mechanisms of radioprotection by dietary carotenoids is reported. An ongoing open-labware project to develop a suite of modular sample handling components suited to radiation research is described, as is the development of a new neutron source able to provide directional beams of neutrons

Mental Disorders Among U.S. Military Personnel in the 1990s: Association With High Levels of Health Care Utilization and Early Military Attrition

OBJECTIVE: Epidemiological studies have shown that mental disorders are associated with reduced health-related quality of life, high levels of health care utilization, and work absenteeism. However, measurement of the burden of mental disorders by using population-based methods in large working populations, such as the U.S. military, has been limited. METHOD: Analysis of hospitalizations among all active-duty military personnel (16.4 million person-years) from 1990 to 1999 and ambulatory visits from 1996 to 1999 was conducted by using the Defense Medical Surveillance System. Rates of hospitalization, ambulatory visits, and attrition from military service were compared for persons with mental disorder diagnoses and those with diagnoses in 15 other ICD-9 disease categories. RESULTS: Mental disorders was the leading category of discharge diagnoses among men and the second leading category among women; 13% of all hospitalizations and 23% of all inpatient bed days were attributed to mental disorders. Six percent of the military population received ambulatory services for mental disorders annually in 1998 and 1999. Among a 1-year cohort of personnel, 47% of those hospitalized for the first time for a mental disorder left military service within 6 months. This attrition rate was significantly different from the rate of only 12% after hospitalization for any of the 15 other disease categories (range=11%–18%) (relative risk=4.04, 95% confidence interval=3.91–4.17). The difference remained significant after controlling for effects of age, gender, and duration of service. CONCLUSIONS: Mental disorders appear to represent the most important source of medical and occupational morbidity among active-duty U.S. military personnel. These findings provide new population-based evidence that mental disorders are common, disabling, and costly to society

Resurgence of a Nation’s Radiation Science Driven by its Nuclear Industry Needs

This article describes the radiation facilities and associated sample preparation, management, and analysis equipment currently in place at the Dalton Cumbrian Facility, a facility which opened in 2011 to support the UK’s nuclear industry. Examples of measurements performed using these facilities are presented to illustrate their versatility and the breadth of research they make possible. Results are presented from research which furthers our understanding of radiation damage to polymeric materials, radiolytic yield of gaseous products in situations relevant to nuclear materials, radiation chemistry in light water reactor cooling systems, material chemistry relevant to immobilization of nuclear waste, and radiation-induced corrosion of fuel cladding elements. Applications of radiation chemistry relevant to health care are also described. Research concerning the mechanisms of radioprotection by dietary carotenoids is reported. An ongoing open-labware project to develop a suite of modular sample handling components suited to radiation research is described, as is the development of a new neutron source able to provide directional beams of neutrons