125 research outputs found

    Modeling of ammonothermal growth processes of GaN crystal in large-size pressure systems

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    Gallium nitride (GaN) is a wide-bandgap semiconductor material with a wide array of applications in optoelectronics and electronics. Modeling of the fluid flow and thermal fields is discussed, and simulations of velocity and volumetric-flow-rate profiles in different pressure systems are shown. The nutrient is considered as a porous media bed, and the flow is simulated using the Darcy-Brinkman-Forchheimer model. The resulting governing equations are solved using the finite-volume method. We analyzed the heat and mass transfer behaviors in autoclaves with diameters of 2.22, 4.44, and 10 cm. The effects of baffle design on flow pattern, and heat and mass transfer in different autoclaves are analyzed. For the research-grade autoclave with diameter of 2.22 cm, the constraint for the GaN growth is found to be the growth kinetics and the total area of seed surfaces in the case of baffle opening of 10%. For large-size pressure systems, the concentration profiles change dramatically due to stronger convection at higher Grashof numbers. The volumetric flow rates of the solvent across the baffles are calculated. Since ammonothermal growth experiments are expensive and time consuming, modeling becomes an effective tool for research and optimization of ammonothermal growth processes

    Hydrothermal Instability Of Thermocapillary Convection In Large-Prandtl-Number Liquid Bridges Under Microgravity

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    Linear stability analysis was performed to study the mechanism of transition of thermocapillary convection in liquid bridges with liquid volume ratios ranging from 0.4 to 1.2, aspect ratio of 0.75 and Prandtl number of 100. 2-D governing equations were solved to obtain the steady axi-symmetric basic flow and temperature distributions. 3-D perturbation equations were discretized at the collocation grid points using the Chebyshev-collocation method. Eigenvalues and eigenfunctions were obtained by using the Q-R. method. The predicted critical Marangoni numbers and critical frequencies were compared with data from space experiments. The disturbance of the temperature distribution on the free surface causes the onset of oscillatory convection. It is shown that the origin of instability is related to the hydrothermal origin for convections in large-Prandtl-number liquid bridges. (C) 2007 COSPAR. Published by Elsevier Ltd. All rights reserved

    Application of Flow-Kinetics Model To the Pvt Growth of Sic Crystals

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    A 2-D flow-kinetics model for the PVT growth has been used to describe the phenomena of multi-phase flow, mass transfer and kinetics in the growth process of SiC crystals. The model couples the 2-D gas flow calculations and the growth kinetics at the crystal interface. We calculated the axisymmetric flow field and species concentration field as well as growth rate profile by a finite volume-based code. Species transfer in the cavity is dominated by the diffusion at growth pressures of 8-14 kPa. Supersaturation at the crystal interface is less than 1 Pa at growth pressures of 8-14 kPa. (c) 2006 Elsevier B.V. All rights reserved

    Spatial Distribution of Human Schistosoma japonicum Infections in the Dongting Lake Region, China

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    BACKGROUND: The aim of this study was to spatially model the effect of demographic, reservoir hosts and environmental factors on human Schistosoma japonicum infection prevalence in the Dongting Lake area of Hunan Province, China and to determine the potential of each indicator in targeting schistosomiasis control. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional serological, coprological and demographic data were obtained from the 2004 nationwide periodic epidemiologic survey for Hunan Province. Environmental data were downloaded from the USGS EROS data centre. Bayesian geostatistical models were employed for spatial analysis of the infection prevalence among study participants. A total of 47,139 participants from 47 administrative villages were selected. Age, sex and occupation of residents and the presence of infected buffaloes and environmental factors, i.e. NDVI, distance to the lake and endemic type of setting, were significantly associated with S. japonicum infection prevalence. After taking into account spatial correlation, however, only demographic factors (age, sex and occupation) and the presence of infected buffaloes remained significant indicators. CONCLUSIONS/SIGNIFICANCE: Long established demographic factors, as well presence of host reservoirs rather than environmental factors are driving human transmission. Findings of this work can be used for epidemiologic surveillance and for the future planning of interventions in the Dongting Lake area of Hunan Province

    Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study

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    <p>Abstract</p> <p>Background</p> <p>In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of the 180–185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care.</p> <p>Methods/Design</p> <p>Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE) resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM). It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance.</p> <p>Discussion</p> <p>On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The results of this study will lead to an evidence based drug treatment of hypothermic neonatal patients. Results will be published in a national web based evidence based paediatric formulary, peer reviewed journals and international paediatric drug references.</p> <p>Trial registration</p> <p>NTR2529.</p

    Arabidopsis Fatty Acid Desaturase FAD2 Is Required for Salt Tolerance during Seed Germination and Early Seedling Growth

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    Fatty acid desaturases play important role in plant responses to abiotic stresses. However, their exact function in plant resistance to salt stress is unknown. In this work, we provide the evidence that FAD2, an endoplasmic reticulum localized ω-6 desaturase, is required for salt tolerance in Arabidopsis. Using vacuolar and plasma membrane vesicles prepared from the leaves of wild-type (Col-0) and the loss-of-function Arabidopsis mutant, fad2, which lacks the functional FAD2, we examined the fatty acid composition and Na+-dependent H+ movements of the isolated vesicles. We observed that, when compared to Col-0, the level of vacuolar and plasma membrane polyunsaturation was lower, and the Na+/H+ exchange activity was reduced in vacuolar and plasma membrane vesicles isolated from fad2 mutant. Consistent with the reduced Na+/H+ exchange activity, fad2 accumulated more Na+ in the cytoplasm of root cells, and was more sensitive to salt stress during seed germination and early seedling growth, as indicated by CoroNa-Green staining, net Na+ efflux and salt tolerance analyses. Our results suggest that FAD2 mediated high-level vacuolar and plasma membrane fatty acid desaturation is essential for the proper function of membrane attached Na+/H+ exchangers, and thereby to maintain a low cytosolic Na+ concentration for salt tolerance during seed germination and early seedling growth in Arabidopsis

    The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants.</p> <p>Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit.</p> <p>Methods/Design</p> <p>TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling".</p> <p>Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods.</p> <p>Sample size</p> <p>At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months.</p> <p>Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited.</p> <p>Primary outcome</p> <p>Combined rate of mortality and severe neurodevelopmental impairment in survivors at 18 months of age. Neurodevelopmental impairment will be defined as any of:</p> <p>• Bayley mental developmental scale score less than 70</p> <p>• Gross Motor Function Classification System Levels III – V</p> <p>• Bilateral cortical visual impairments</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN89547571</p

    P1 receptors and cytokine secretion

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    Evidence has accumulated in the last three decades to suggest tissue protection and regeneration by adenosine in multiple different cell types. Adenosine produced in hypoxic or inflamed environments reduces tissue injury and promotes repair by receptor-mediated mechanisms. Among other actions, regulation of cytokine production and secretion by immune cells, astrocytes and microglia (the brain immunocytes) has emerged as a main mechanism at the basis of adenosine effects in diseases characterized by a marked inflammatory component. Many recent studies have highlighted that signalling through A1 and A2A adenosine receptors can powerfully prevent the release of pro-inflammatory cytokines, thus inhibiting inflammation and reperfusion injury. However, the activation of adenosine receptors is not invariably protective of tissues, as signalling through the A2B adenosine receptor has been linked to pro-inflammatory actions which are, at least in part, mediated by increased release of pro-inflammatory cytokines from epithelial cells, astrocytes and fibroblasts. Here, we discuss the multiple actions of P1 receptors on cytokine secretion, by analyzing, in particular, the role of the various adenosine receptor subtypes, the complex reciprocal interplay between the adenosine and the cytokine systems, their pathophysiological significance and the potential of adenosine receptor ligands as new anti-inflammatory agents

    Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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    BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders

    Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

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    Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different
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