Test and Analysis of a Buckling-Critical Large-Scale Sandwich Composite Cylinder

Structural stability is an important design consideration for launch-vehicle shell structures and it is well known that the buckling response of such shell structures can be very sensitive to small geometric imperfections. As part of an effort to develop new buckling design guidelines for sandwich composite cylindrical shells, an 8-ft-diameter honeycomb-core sandwich composite cylinder was tested under pure axial compression to failure. The results from this test are compared with finite-element-analysis predictions and overall agreement was very good. In particular, the predicted buckling load was within 1% of the test and the character of the response matched well. However, it was found that the agreement could be improved by including composite material nonlinearity in the analysis, and that the predicted buckling initiation site was sensitive to the addition of small bending loads to the primary axial load in analyses

The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation

Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated.Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually.We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Can Imazapic Increase Native Species Abundance in Cheatgrass (Bromus tectorum) Invaded Native Plant Communities?

Native plant communities invaded by cheatgrass (Bromus tectorum L.) are at risk of unnatural high intensity fires and conversion to cheatgrass monocultures. Management strategies that reduce cheatgrass abundance may potentially allow native species to expand and minimize further cheatgrass invasion. We tested whether the selective herbicide imazapic is effective in reducing cheatgrass and ‘‘releasing’’ native species in a semiarid grassland and shrub steppe in north-central Oregon. The experiment consisted of a completely randomized design with two treatments (sprayed with 70 g ai ha-1 of imazapic and unsprayed) and three replicates of each treatment applied to either 2.5 or 4 ha plots. We repeated this experiment in three different sites dominated by the following native species: 1) bluebunch wheatgrass (Pseudoroegneria spicata [Pursh] A. Löve ssp. spicata) and needle and thread (Hesperostipa comata [Trin. Rupr.] Barkworth), 2) needle and thread and Sandberg bluegrass (Poa secunda J. Presl), and 3) big sagebrush (Artemisia tridentata Nutt.). Nested frequency of all plant species in 1-m2 quadrats was collected for 1 yr pretreatment and 4 yr posttreatment. In all three sites, cheatgrass frequencies were significantly lower in sprayed plots than unsprayed plots for 3-4 yr posttreatment (P<0.1). Other annual plant species were also impacted by imazapic, but the effects were highly variable by species and site. Only two native perennial species, hoary tansyaster (Machaeranthera canescens [Pursh] Gray) and big sagebrush, increased in sprayed plots, and increases occurred only at two sites. These results suggest that a short-term reduction in cheatgrass alone is not an effective strategy for increasing the abundance of most native perennial plant species.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Cinnabar Moth Dispersal

Data from mark-recapture study on cinnabar moths conducted at Cogswell Foster, OR, from 1986-05-29 through 1986-06-12. Data on captured and marked moths includes a number identifier, gender, wing wear (low, high), post-release behavior (mobile or immobile), capture/recapture locations (X/Y coordinates of study area, plot number, and categorical location relative to boundary of study area), and date. X/Y coordinates of initial capture are missing for some moths (value of NA)

Can Imazapic Increase Native Species Abundance in Cheatgrass (Bromus tectorum) Invaded Native Plant Communities?

Native plant communities invaded by cheatgrass (Bromus tectorum L.) are at risk of unnatural high intensity fires and conversion to cheatgrass monocultures. Management strategies that reduce cheatgrass abundance may potentially allow native species to expand and minimize further cheatgrass invasion. We tested whether the selective herbicide imazapic is effective in reducing cheatgrass and ‘‘releasing’’ native species in a semiarid grassland and shrub steppe in north-central Oregon. The experiment consisted of a completely randomized design with two treatments (sprayed with 70 g ai ha-1 of imazapic and unsprayed) and three replicates of each treatment applied to either 2.5 or 4 ha plots. We repeated this experiment in three different sites dominated by the following native species: 1) bluebunch wheatgrass (Pseudoroegneria spicata [Pursh] A. Löve ssp. spicata) and needle and thread (Hesperostipa comata [Trin. Rupr.] Barkworth), 2) needle and thread and Sandberg bluegrass (Poa secunda J. Presl), and 3) big sagebrush (Artemisia tridentata Nutt.). Nested frequency of all plant species in 1-m2 quadrats was collected for 1 yr pretreatment and 4 yr posttreatment. In all three sites, cheatgrass frequencies were significantly lower in sprayed plots than unsprayed plots for 3-4 yr posttreatment (P<0.1). Other annual plant species were also impacted by imazapic, but the effects were highly variable by species and site. Only two native perennial species, hoary tansyaster (Machaeranthera canescens [Pursh] Gray) and big sagebrush, increased in sprayed plots, and increases occurred only at two sites. These results suggest that a short-term reduction in cheatgrass alone is not an effective strategy for increasing the abundance of most native perennial plant species.The Rangeland Ecology & Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202