System impacts of solar dynamic and growth power systems on space station

Concepts for the 1990's space station envision an initial operational capability with electrical power output requirements of approximately 75 kW and growth power requirements in the range of 300 kW over a period of a few years. Photovoltaic and solar dynamic power generation techniques are contenders for supplying this power to the space station. A study was performed to identify growth power subsystem impacts on other space station subsystems. Subsystem interactions that might suggest early design changes for the space station were emphasized. Quantitative analyses of the effects of power subsystem mass and projected area on space station controllability and reboost requirements were conducted for a range of growth station configurations. Impacts on space station structural dynamics as a function of power subsystem growth were also considered

Periferne osteoporotske frakture osim kuka - epidemiologija i značenje

Fractures are the most serious consequence of osteoporosis. Non-vertebral and non-hip fractures are seldom recognised as important, even though they account for the majority of all fractures. The most prevalent localisations are distal radius, proximal humerus, ribs, clavicle, and the pelvis. According to the results from large phase III clinical trials for placebo groups, their incidence ranges from 4.9 % to 12.0 %. Hospital morbidity data in Croatia in 2006 show that peripheral non-hip fractures ranked among the leading fifteen injuries, accounting for 23.7 % of all injuries in patients aged 60 years and above. Risk factors for non-hip and non-vertebral fractures are similar to other osteoporotic fractures, and the main are low bone mineral density and earlier fractures. Quality of life is considerably affected by these fractures, and medical costs are very high, soaring as high as 36.9 % of all national medical costs in the USA. Nonvertebral non-hip fractures need more attention, which was also recognised by the European regulatory bodies that approve use of anti-osteoporotic drugs.Prijelomi su najozbiljnija posljedica osteoporoze. Iako čine većinu svih fraktura, nevertebralne frakture osim kuka rijetko se prepoznaju kao značajne. Najčešće lokalizacije tih prijeloma su: distalni dio radijusa, proksimalni dio humerusa, rebra, klavikula i zdjelica. Prema rezultatima iz placebo-grupa III. faze velikih kliničkih ispitivanja raspon njihove incidencije iznosi između 4,9 % i 12,0 %. Prema podacima bolničkog pobolijevanja za 2006. g. u Hrvatskoj, među 15 vodećih ozljeda u dobnoj grupi 60 i više godina 23,7 % bile su periferne frakture osim kuka. Čimbenici rizika za nevertebralne frakture osim onih kuka slični su kao i za druge osteoporotske frakture gdje središnje mjesto imaju niska mineralna gustoća kosti i prethodne frakture. Ove frakture imaju velik utjecaj na kvalitetu `ivota, a njihovi su troškovi vrlo visoki, tako da u SAD-u iznose čak 36.9 % svih nacionalnih medicinskih troškova. Nevertebralne frakture osim kuka zahtijevaju veću pozornost, što su i prepoznala europska regulatorna tijela koja odobravaju upotrebu antiosteoporotskih lijekova

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes

A Large Gene Network in Immature Erythroid Cells Is Controlled by the Myeloid and B Cell Transcriptional Regulator PU.1

PU.1 is a hematopoietic transcription factor that is required for the development of myeloid and B cells. PU.1 is also expressed in erythroid progenitors, where it blocks erythroid differentiation by binding to and inhibiting the main erythroid promoting factor, GATA-1. However, other mechanisms by which PU.1 affects the fate of erythroid progenitors have not been thoroughly explored. Here, we used ChIP-Seq analysis for PU.1 and gene expression profiling in erythroid cells to show that PU.1 regulates an extensive network of genes that constitute major pathways for controlling growth and survival of immature erythroid cells. By analyzing fetal liver erythroid progenitors from mice with low PU.1 expression, we also show that the earliest erythroid committed cells are dramatically reduced in vivo. Furthermore, we find that PU.1 also regulates many of the same genes and pathways in other blood cells, leading us to propose that PU.1 is a multifaceted factor with overlapping, as well as distinct, functions in several hematopoietic lineages

The Double-stranded RNA–dependent Protein Kinase Differentially Regulates Insulin Receptor Substrates 1 and 2 in HepG2 Cells

The RNA-dependent protein kinase (PKR), initially known as a virus infection response protein, is found to differentially regulate two major players in the insulin signaling pathway, IRS1 and IRS2. PKR up-regulates the inhibitory phosphorylation of IRS1 and the expression of IRS2 at the transcriptional level

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)