A Blended Global Snow Product using Visible, Passive Microwave and Scatterometer Satellite Data

A joint U.S. Air Force/NASA blended, global snow product that utilizes Earth Observation System (EOS) Moderate Resolution Imaging Spectroradiometer (MODIS), Advanced Microwave Scanning Radiometer for EOS (AMSR-E) and QuikSCAT (Quick Scatterometer) (QSCAT) data has been developed. Existing snow products derived from these sensors have been blended into a single, global, daily, user-friendly product by employing a newly-developed Air Force Weather Agency (AFWA)/National Aeronautics and Space Administration (NASA) Snow Algorithm (ANSA). This initial blended-snow product uses minimal modeling to expeditiously yield improved snow products, which include snow cover extent, fractional snow cover, snow water equivalent (SWE), onset of snowmelt, and identification of actively melting snow cover. The blended snow products are currently 25-km resolution. These products are validated with data from the lower Great Lakes region of the U.S., from Colorado during the Cold Lands Processes Experiment (CLPX), and from Finland. The AMSR-E product is especially useful in detecting snow through clouds; however, passive microwave data miss snow in those regions where the snow cover is thin, along the margins of the continental snowline, and on the lee side of the Rocky Mountains, for instance. In these regions, the MODIS product can map shallow snow cover under cloud-free conditions. The confidence for mapping snow cover extent is greater with the MODIS product than with the microwave product when cloud-free MODIS observations are available. Therefore, the MODIS product is used as the default for detecting snow cover. The passive microwave product is used as the default only in those areas where MODIS data are not applicable due to the presence of clouds and darkness. The AMSR-E snow product is used in association with the difference between ascending and descending satellite passes or Diurnal Amplitude Variations (DAV) to detect the onset of melt, and a QSCAT product will be used to map areas of snow that are actively melting

Cracking and Corrosion of Composite Tubes in Black Liquor Recovery Boiler Primary Air Ports

Black liquor recovery boilers are an essential part of kraft mills. Their design and operating procedures have changed over time with the goal of providing improved boiler performance. These performance improvements are frequently associated with an increase in heat flux and/or operating temperature with a subsequent increase in the demand on structural materials associated with operation at higher temperatures and/or in more corrosive environments. Improvements in structural materials have therefore been required. In most cases the alternate materials have provided acceptable solutions. However, in some cases the alternate materials have solved the original problem but introduced new issues. This report addresses the performance of materials in the tubes forming primary air port openings and, particularly, the problems associated with use of stainless steel clad carbon steel tubes and the solutions that have been identified

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Joint Analysis Of Psychiatric Disorders Increases Accuracy Of Risk Prediction For Schizophrenia, Bipolar Disorder, And Major Depressive Disorder

Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk

Upregulated copper transporters in hypoxia-induced pulmonary hypertension.

Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu) plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX), a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2) also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC). In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α) with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness

FIBCD1 is an endocytic GAG receptor associated with a novel neurodevelopmental disorder

Abstract Whole‐exome sequencing of two patients with idiopathic complex neurodevelopmental disorder (NDD) identified biallelic variants of unknown significance within FIBCD1, encoding an endocytic acetyl group‐binding transmembrane receptor with no known function in the central nervous system. We found that FIBCD1 preferentially binds and endocytoses glycosaminoglycan (GAG) chondroitin sulphate‐4S (CS‐4S) and regulates GAG content of the brain extracellular matrix (ECM). In silico molecular simulation studies and GAG binding analyses of patient variants determined that such variants are loss‐of‐function by disrupting FIBCD1‐CS‐4S association. Gene knockdown in flies resulted in morphological disruption of the neuromuscular junction and motor‐related behavioural deficits. In humans and mice, FIBCD1 is expressed in discrete brain regions, including the hippocampus. Fibcd1 KO mice exhibited normal hippocampal neuronal morphology but impaired hippocampal‐dependent learning. Further, hippocampal synaptic remodelling in acute slices from Fibcd1 KO mice was deficient but restored upon enzymatically modulating the ECM. Together, we identified FIBCD1 as an endocytic receptor for GAGs in the brain ECM and a novel gene associated with an NDD, revealing a critical role in nervous system structure, function and plasticity

Hypoxia-mediated upregulation of mRNA expression of Cu transporters (CTR1, ATP7A) and lysyl oxidase (LOX) is associated with an increase in Cu transportation in human pulmonary arterial smooth muscle cells (PASMC).

<p>A: Real-time RT-PCR analysis on ATP7A, CTR1, and LOX (left panel) and ⁶⁴Cu uptake (mean±SE) in human PASMC exposed to normoxia (Nor) and hypoxia (Hyp, 3% O₂ for 48 hrs, n = 3; right panel). B: Real-time RT-PCR analysis on ATP7A, CTR1, and LOX (left panel) and ⁶⁴Cu uptake (mean±SE, right panel) in human PASMC treated with vehicle (Cont) and CoCl₂ (100 µM for 48 hrs, n = 3; right pane). Lactate dehydrogenase (LDH) and erythropoietin (EPO) were used as positive controls. *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 vs. Hyp or CoCl₂.</p

PASMC motility is dependent on Cu and the Cu-dependent PASMC motility is augmented by hypoxia.

<p>Cell motility was determined by a scratch wound assay over a period of 12: Representative images showing normoxic (Nor) and hypoxic (Hyp) PASMC immediately (0 hr) or 12 hrs after scratch with a sterile pipette in the absence (Control) or presence (BCS) of 200 µM BCS (a Cu chelator). B: Representative images showing control (-CoCl₂) and 100-µm CoCl₂-treated PASMC immediately (0 hr) or 12 hrs after scratch in the absence (Control) or presence (BCS) of BCS. C: Summarized data (mean±SE) showing gap closure (<i>a</i>) measured at 12 hr in Nor and Hyp PASMC treated with (BCS) or without (Control) BCS. **<i>P</i><0.01 vs. Control. The Cu-dependent cell motility (<i>b</i>) was determined by the percent changes in gap closure between Control and BCS-treated PASMC under Nor and Hyp conditions. *<i>P</i><0.05 vs. Nor. D: Summarized data (mean±SE) showing gap closure (<i>a</i>) measured at 12 hr in PASMC treated with (+CoCl₂) or without (-CoCl₂) CoCl₂ in the absence (Control) or presence (BCS) of BCS. *<i>P</i><0.05 vs. Control. The Cu-dependent cell motility (<i>b</i>) was determined by the percent changes in gap closure between Control and BCS-treated PASMC in the absence (-) or presence (+) of CoCl₂.</p

Inhibition of LOX downregulates PCNA (a marker for cell proliferation) and Bcl–2 (an anti-apoptotic protein) in human PASMC during hypoxia.

<p>A: Western blot analysis on PCNA and Bcl–2 in hypoxic PASMC treated with (+) or without (-) the irreversible LOX inhibitor βAPN (for 48 hrs). B: Summarized data (mean±SE) showing PCNA (left panel) and Bcl–2 (right panel) protein levels in control PASMC (open bars) and PASMC treated with βAPN (solid bars). **<i>P</i><0.01 vs. Control.</p