Investigation of parallel efficiency of an adaptive flow solver

AbstractParallel efficiency, in a domain decomposition based approach, strongly depends on a partitioning quality. For an adaptive simulation partitioning quality is lost due to the dynamic modification of the computational mesh. Maintaining high efficiency of parallelization requires rebalancing of the numerical load. This paper presents numerical experiment with adaptive and dynamically load balanced flow application. It is shown that through a relatively inexpensive process of repartitioning high parallel efficiency is maintained

The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells

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Nucleophilic activation of carbon monoxide. A kinetics investigation of the reaction of chloride with triruthenium dodecacarbonyl

Kinetics studies of the reaction of the triruthenium cluster Ru3(CO)12 with the “highly dissociated” chloride salt [PPN]Cl to give the Ru3(CO)11Cl− anion in THF/CH2Cl2 solutions show a rate law first order in [Cl−] and in [Ru3(CO)12]. Rates are significantly higher in 90/10 than in 80/10 (v/v) THF/CH2Cl2 solutions, and the reactivity order is qualitatively the inverse of that of solvent acceptor properties. No intermediates were observed in the reactions. For Pco > 0.1 atm, the rates appeared nearly CO independent although systematic small rate increases were observed at lower PCO. It is suggested that the reaction with Cl− may involve competitive nucleophilic attack at both metal and carbonyl centers. © 1993, American Chemical Society. All rights reserved

The potential of dietary treatment in patients with glycogen storage disease type IV

There is paucity of literature on dietary treatment in glycogen storage disease (GSD) type IV and formal guidelines are not available. Traditionally, liver transplantation was considered the only treatment option for GSD IV. In light of the success of dietary treatment for the other hepatic forms of GSD, we have initiated this observational study to assess the outcomes of medical diets, which limit the accumulation of glycogen. Clinical, dietary, laboratory, and imaging data for 15 GSD IV patients from three centres are presented. Medical diets may have the potential to delay or prevent liver transplantation, improve growth and normalize serum aminotransferases. Individual care plans aim to avoid both hyperglycaemia, hypoglycaemia and/or hyperketosis, to minimize glycogen accumulation and catabolism, respectively. Multidisciplinary monitoring includes balancing between traditional markers of metabolic control (ie, growth, liver size, serum aminotransferases, glucose homeostasis, lactate, and ketones), liver function (ie, synthesis, bile flow and detoxification of protein), and symptoms and signs of portal hypertension

An evolutionary timeline of the oxytocin signaling pathway.

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500-1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue

Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia

Patients within the WHO-subgroup of t(6;9)-positive acute myeloid leukemia (AML) differ from other AML subgroups as they are characterised by younger age and a grim prognosis. Leukemic transformation can often be attributed to single chromosomal aberrations encoding oncogenes, in the case of t(6;9)-AML to the fusion protein DEK-CAN (also called DEK-NUP214). As being a rare disease there is the urgent need for models of t(6;9)-AML. The only cell line derived from a t(6;9)-AML patient currently available is FKH1. By using phospho-proteomics on FKH1 cells, we found a strongly activated ABL1 kinase. Further investigation revealed the presence of ETV6-ABL1. This finding renders necessary to determine DEK-CAN- and ETV6-ABL1-related features when using FKH1. This can be done as ETV6-ABL1 activity in FKH1 is responsive to imatinib. Nevertheless, we provided evidence that both SFK and mTOR activation in FKH1 are DEK-CAN-related features as they were activated also in other t(6;9) and DEK-CAN-positive models. The activation of STAT5 previously shown to be strong in t(6;9)-AML and activated by DEK-CAN is regulated in FKH1 by both DEK-CAN and ETV6-ABL1. In conclusion, FKH1 cells still represent a model for t(6;9)-AML and could serve as model for ETV6-ABL1-positive AML if the presence of these leukemia-inducing oncogenes is adequately considered. Taken together, all our results provide clear evidence of novel and specific interdependencies between leukemia-inducing oncogenes and cancer signaling pathways which will influence the design of therapeutic strategies to better address the complexity of cancer signaling

A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease

Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased β-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.</p

Ti alloy with enhanced machinability in UAT turning

Metastable β-titanium alloys such as Ti 15V 3Al 3Cr 3Sn are of great technological interest thanks to their high fatigue strength-to-density ratio. However, their high hardness and poor machinability increase machining costs. Additionally, formation of undesirable long chips increases the machining time. To address those issues, a metastable β-titanium alloy (Ti 15V 3Al 3Cr 2Zr 0.9La) with enhanced machinability was developed to produce short chips even at low cutting speeds. A hybrid ultrasonically assisted machining technique, known to reduce cutting forces, was employed in this study. Cutting force components and surface quality of the finished work-pieces were analyzed for a range of cutting speeds in comparison with those for more traditional Ti 15V 3Al 3Cr 3Sn. The novel alloy demonstrated slightly improved machining characteristics at higher cutting speeds and is now ready for industrial applications