Grown-in defects and defects produced by 1-Me electron irradiated in Al0.3Ga0.7As P-N junction solar cells

Studies of grown-in defects and defects produced by the one-MeV electron irradiation in Al sub 0.3 Ga sub 0.7As p-n junction solar cells fabricated by liquid phase epitaxial (LPE) technique were made for the unirradiated and one-MeV electron irradiated samples, using DLTS and C-V methods. Defect and recombination parameters such as energy level, defect density, carrier capture cross sections and lifetimes were determined for various growth, annealing, and irradiation conditions

Insulin Receptor and the Kidney: Nephrocalcinosis in Patients with Recessive INSR Mutations.

BACKGROUND/AIMS: Donohue and Rabson-Mendenhall syndrome are rare autosomal recessive disorders caused by mutations in the insulin receptor gene, INSR. Phenotypic features include extreme insulin resistance, linear growth retardation, paucity of fat and muscle, and soft tissue overgrowth. The insulin receptor is also expressed in the kidney, where animal data suggest it plays a role in glomerular function and blood pressure (BP) regulation, yet such a role in the human kidney is untested. Patients with biallelic INSR mutations provide a rare opportunity to ascertain its role in man. METHODS: Retrospective review of patients with INSR mutations. Data for BP, renal imaging, plasma creatinine and electrolyte levels, as well as urine protein, albumin and calcium excretion were sought from the treating clinicians. RESULTS: From 33 patients with INSR mutations, data were available for 17 patients. Plasma creatinine was low (mean ± SD: 25 ± 9 μmol/l) and mean plasma electrolyte concentrations were within the normal range (n = 13). Systolic BP ranged between the 18th and 91st percentile for age, sex, height and weight (n = 9; mean ± SD: 49 ± 24). Twenty-four-hour urinary calcium data were available from 10 patients and revealed hypercalciuria in all (mean ± SD: 0.32 ± 0.17 mmol/kg/day; normal <0.1). Nephrocalcinosis was present in all patients (n = 17). Urinary albumin excretion (n = 7) ranged from 4.3-122.5 μg/min (mean ± SD: 32.4 ± 41.0 μg/min; normal <20). CONCLUSIONS: INSR dysfunction is associated with hypercalciuria and nephrocalcinosis. No other consistent abnormality of renal function was noted. Normotension and stable glomerular function with only moderate proteinuria is in contrast to genetically modified mice who have elevated BP and progressive diabetic nephropathy

Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes.

Volcanic emissions are a critical pathway in Earth's carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes-3760 ± [600, 310] tons day-1 CO2 and 5150 ± [730, 340] tons day-1 SO2-for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near-real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates

Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes

Volcanic emissions are a critical pathway in Earth’s carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes—3760 ± [600, 310] tons day−1 CO2 and 5150 ± [730, 340] tons day−1 SO2—for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near–real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates

Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes

Volcanic emissions are a critical pathway in Earth's carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes-3760 ± [600, 310] tons day-1CO2and 5150 ± [730, 340] tons day-1SO2-for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2flux and enable near-real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates

Aerial strategies advance volcanic gas measurements at inaccessible, strongly degassing volcanoes

Volcanic emissions are a critical pathway in Earth’s carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes—3760 ± [600, 310] tons day−1 CO2 and 5150 ± [730, 340] tons day−1 SO2—for a strong yet previously uncharacterized volcanic emitter: Manam, Papua New Guinea. The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near–real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates

STK35L1 Associates with Nuclear Actin and Regulates Cell Cycle and Migration of Endothelial Cells

BACKGROUND: Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1) to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1) to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold) in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a) leading to G(1) arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays. CONCLUSION/SIGNIFICANCE: The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear actin might be critical in the regulation of these fundamental endothelial functions

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial