Benchmark of CFD Simulations Using Temperatures Measured within an Enclosed Array of Heater Rods Oriented Vertically and Horizontally

Experiments and computational fluid dynamics/radiation heat transfer simulations of an 8 8 array of heated rods within an aluminum enclosure are performed. This configuration represents a region inside the channel of a spent boiling water reactor (BWR) fuel assembly between two consecutive spacer plates. The heater rods can be oriented horizontally or vertically to represent transport or storage conditions, respectively. The measured and simulated rod-to-wall temperature differences are compared for various heater rod power levels (100, 200, 300, 400 and 500W), gases (Helium and Nitrogen), enclosure wall temperatures, pressures (1, 2 and 3 atm) and orientations (Horizontal and Vertical) to assess the accuracy of the computational fluid dynamics (CFD) code. For analysis of spent nuclear fuel casks, it is crucial to predict the temperature of the hottest rods in an assembly to ensure that none of the fuel cladding exceeds its temperature limit. The measured temperatures are compared to those determined using CFD code to assess the adequacy of the computer code. Simulations show that temperature gradients are much steeper near the enclosure walls than they are near the center of the heater rod array. The measured maximum heater rod temperatures are above the center of heater rod array for nitrogen experiments in both horizontal and vertical orientations, whereas for helium the maximum temperatures are at the center of heater rod array irrespective of the orientation due to the high thermal conductivity of the helium gas. The measured temperatures of rods at symmetric locations are not identical, and the difference is larger for rods close to the enclosure wall than for those far from it. Small but uncontrolled ii deviations of the rod positions away from the design locations may cause these differences. For 2-inch insulated nitrogen experiment in vertical orientation with 1 atm pressure and a total heater rod power of 500 W, the maximum measured heater rod and enclosure wall temperatures are 375oC and 285oC respectively with the measured rod-towall temperature difference of 90oC. The simulated rod-to-wall temperature difference for this case is 91.2oC. The simulations reproduce the measured temperature profiles. The ∆TSIM vs. ∆TMEA for all experiments (i.e. N = 3384 measured/simulated temperatures), the linear regression line " ∆TSIM,LR = 0.97∆TMEA + 0.8°C" shows that the simulations slightly but systematically under predict the heater rod temperatures with 95% of the simulated temperatures are within 11°C. The ∆TSIM vs. ∆TMEA for the hottest heater rod temperatures yields a linear regression line "∆TSIM = 1.01∆TMEA - 1.1oC" with 95% of the simulated temperatures are within 7.3°C which is 34% smaller than it was for all the temperatures. These results can be used to assess the accuracy of using simulations to design spent nuclear fuel transport and storage systems

Coenzyme Q10 in the treatment of mitochondrial disease

Currently, there is a paucity of available treatment strategies for oxidative phosphorylation disorders. Coenzyme Q10 (CoQ10) and related synthetic quinones are the only agents to date that have proven to be beneficial in the treatment of these heterogeneous disorders. The therapeutic efficacy of CoQ10 is not restricted to patients with an underlying CoQ10 deficiency and is thought to result from its ability to restore electron flow in the mitochondrial respiratory chain (MRC) as well as to increase the cellular antioxidant capacity. At present, however, there is no consensus on the appropriate dosage or therapeutic plasma level of CoQ10, and this information will be required before CoQ10 can be utilized effectively in the treatment of mitochondrial disease. The following review will outline our current knowledge on the use of CoQ10 in the treatment of MRC disorders and primary CoQ10 deficiencies. Keyword

Strain in epitaxial MnSi films on Si(111) in the thick film limit studied by polarization-dependent extended x-ray absorption fine structure

We report a study of the strain state of epitaxial MnSi films on Si(111) substrates in the thick film limit (100-500~\AA) as a function of film thickness using polarization-dependent extended x-ray absorption fine structure (EXAFS). All films investigated are phase-pure and of high quality with a sharp interface between MnSi and Si. The investigated MnSi films are in a thickness regime where the magnetic transition temperature $T_\mathrm{c}$ assumes a thickness-independent enhanced value of $\geq$43~K as compared with that of bulk MnSi, where $T_\mathrm{c} \approx 29~{\rm K}$. A detailed refinement of the EXAFS data reveals that the Mn positions are unchanged, whereas the Si positions vary along the out-of-plane [111]-direction, alternating in orientation from unit cell to unit cell. Thus, for thick MnSi films, the unit cell volume is essentially that of bulk MnSi --- except in the vicinity of the interface with the Si substrate (thin film limit). In view of the enhanced magnetic transition temperature we conclude that the mere presence of the interface, and its specific characteristics, strongly affects the magnetic properties of the entire MnSi film, even far from the interface. Our analysis provides invaluable information about the local strain at the MnSi/Si(111) interface. The presented methodology of polarization dependent EXAFS can also be employed to investigate the local structure of other interesting interfaces.Comment: 11 pages, 10 figure

APEnet+: high bandwidth 3D torus direct network for petaflops scale commodity clusters

We describe herein the APElink+ board, a PCIe interconnect adapter featuring the latest advances in wire speed and interface technology plus hardware support for a RDMA programming model and experimental acceleration of GPU networking; this design allows us to build a low latency, high bandwidth PC cluster, the APEnet+ network, the new generation of our cost-effective, tens-of-thousands-scalable cluster network architecture. Some test results and characterization of data transmission of a complete testbench, based on a commercial development card mounting an Altera FPGA, are provided.Comment: 6 pages, 7 figures, proceeding of CHEP 2010, Taiwan, October 18-2

Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission

Defects of mitochondrial dynamics are emerging causes of neurological disease. In two children presenting with severe neurological deterioration following viral infection we identified a novel homozygous STAT2 mutation, c.1836C4A (p.Cys612Ter), using whole exome sequencing. In muscle and fibroblasts from these patients, and a third unrelated STAT2-deficient patient, we observed extremely elongated mitochondria. Western blot analysis revealed absence of the STAT2 protein and that the mitochondrial fission protein DRP1 (encoded by DNM1L) is inactive, as shown by its phosphorylation state. All three patients harboured 15 decreased levels of DRP1 phosphorylated at serine residue 616 (P-DRP1S616), a post-translational modification known to activate DRP1, and increased levels of DRP1 phosphorylated at serine 637 (P-DRP1S637), associated with the inactive state of the DRP1 GTPase. Knockdown of STAT2 in SHSY5Y cells recapitulated the fission defect, with elongated mitochondria and decreased PDRP1 S616 levels. Furthermore the mitochondrial fission defect in patient fibroblasts was rescued following lentiviral transduction with wild-type STAT2 in all three patients, with normalization of mitochondrial length and increased P-DRP1S616 levels. Taken 20 together, these findings implicate STAT2 as a novel regulator of DRP1 phosphorylation at serine 616, and thus of mitochondrial fission, and suggest that there are interactions between immunity and mitochondria. This is the first study to link the innate immune system to mitochondrial dynamics and morphology. We hypothesize that variability in JAK-STAT signalling may contribute to the phenotypic heterogeneity of mitochondrial disease, and may explain why some patients with underlying mitochondrial disease decompensate after seemingly trivial viral infections. Modulating JAK-STAT activity may represent a novel 25 therapeutic avenue for mitochondrial diseases, which remain largely untreatable. This may also be relevant for more common neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s diseases, in which abnormalities of mitochondrial morphology have been implicated in disease pathogenesis

Dextran and its potential use as tablet excipient

Dextrans are a class of carbohydrate polymers extensively applied in pharmaceutical applications, particularly as drug conjugate macromolecular carriers or drug delivery systems. These polysaccharides improve the stability of the therapeutics enabling also the control of their release, via either the parenteral and or oral routes. In the latter case, due to their gel forming ability they may have potential as hydrophilic matrix tablets for sustained drug release. In this paper, we investigated the behaviour of different molecular weight (1, 40, 500 and 2300 kDa) dextrans as tabletting excipients. Powder particle size and hygroscopic studies have been reported, together with tabletability, tablet stability and tablet swelling. Moreover we use tramadol as model compound to evaluate the ability of dextrans to control drug dissolution. The results suggest that dextrans with lower molecular weights may be a promising excipient to be used as filler for immediate release tablets, due to their good tabletability and fast dissolution rate, while dextrans with higher molecular weights could be an efficient disintegrant due to their swelling ability

Consensus: guidelines: best practices for detection, assessment and management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis

BACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials. AIMS: This publication focuses on best practices concerning the detection, monitoring, diagnosis and management of suspected acute DILI during clinical trials in patients with NASH. METHODS: This is one of several papers developed by the IQ DILI Initiative, comprised of members from 15 pharmaceutical companies, in collaboration with DILI experts from academia and regulatory agencies. This paper is based on extensive literature review, and discussions between industry members with expertise in drug safety and DILI experts from outside industry to achieve consensus on common questions related to this topic. RESULTS: Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules. CONCLUSIONS: This paper provides a framework for the approach to assessment and management of suspected acute DILI during clinical trials in patients with NASH

Racial Disparities in Liver Transplantation for Hepatocellular Carcinoma Are Not Explained by Differences in Comorbidities, Liver Disease Severity, or Tumor Burden

Black patients have higher mortality and are less likely to receive liver transplantation for hepatocellular carcinoma (HCC) than white patients. Reasons for these disparities have not been fully elucidated. Comorbid disease, liver disease severity, cirrhosis etiologies, and tumor characteristics were compared between black and white patients with HCC seen at the Indiana University Academic Medical Center from January 2000 to June 2014. Logistic regression was used to investigate the primary outcome, which was liver transplantation. Log-rank testing was used to compare survival between the two groups. Subgroup analysis explored reasons for failure to undergo liver transplantation in patients within Milan criteria. The cohort included 1,032 (86%) white and 164 (14%) black patients. Black and white patients had similar Model for End-Stage Liver Disease (MELD) and Child-Pugh scores (CPSs). There was a trend toward larger tumor size (5.3 cm versus 4.7 cm; P = 0.05) in black patients; however, Barcelona Clinic Liver Cancer (BCLC) staging and Milan criteria were similar. Black patients were less likely to undergo liver transplantation than white patients; this was a disparity that was not attenuated (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21-0.90) on multivariable analysis. Substance abuse was more frequently cited as the reason black patients within Milan criteria failed to undergo transplantation compared to white patients. Survival was similar between the two groups. Conclusion: Racial differences in patient and tumor characteristics were small and did not explain the disparity in liver transplantation. Higher rates of substance abuse in black patients within Milan criteria who failed to undergo transplantation suggest social factors contribute to this disparity in this cohort

Poor competitiveness of Bradyrhizobium in pigeon pea root colonisation in Indian soils

Background Pigeon pea, a legume crop native to India, is the primary source of protein for more than a billion people in developing countries. The plant can form symbioses with N2-fixing bacteria, however reports of poor crop nodulation in agricultural soils abound. We report here study of the microbiota associated with pigeon pea, with a special focus on the symbiont population in different soils and vegetative and non-vegetative plant growth. Results Location with respect to the plant roots was determined to be the main factor controlling the microbiota followed by developmental stage and soil type. Plant genotype plays only a minor role. Pigeon pea roots have a reduced microbial diversity compared to the surrounding soil and select for Proteobacteria and especially for Rhizobium spp. during vegetative growth. While Bradyrhizobium, a native symbiont of pigeon pea, can be found associating with roots, its presence is dependent on plant variety and soil conditions. A combination of metagenomic survey, strain isolation and co-inoculation with nodule forming Bradyrhizobium spp. and non-N2 fixing Rhizobium spp. demonstrated that the latter is a much more successful coloniser of pigeon pea roots. Conclusions Poor nodulation of pigeon pea in Indian soils may be caused by a poor Bradyrhizobium competitiveness against non-nodulating root colonisers such as Rhizobium. Hence, inoculant strain selection of symbionts for pigeon pea should not only be based on their nitrogen fixation potential but more importantly on their competitiveness in agricultural soils

Older Age and Disease Duration Are Highly Associated with Hepatocellular Carcinoma in Patients with Autoimmune Hepatitis

Background: Hepatocellular carcinoma (HCC) is rare in patients with autoimmune hepatitis (AIH). However, the overall burden of AIH cirrhosis in causing HCC and patients' risk factors are not well understood. Aims: To characterize the proportion of HCC linked to AIH at a large academic health center, and to identify variables associated with HCC in patients with AIH in a case-control study design. Methods: Over a 14.5-year period, medical records of all patients with HCC were reviewed. Cases are AIH patients identified from the cohort, and controls are patients with AIH without HCC. Three controls were randomly chosen from the Genetic Repository of Autoimmune Liver Disease and Coexisting Exposures database for each eligible case. Results: Out of 1250 eligible patients, 20 were linked to AIH (1.6%). Their median age was 64 years, 40% men and 100% Caucasian. Ten percent of AIH patients did not have evidence of cirrhosis at HCC diagnosis. The proportion of HCCs due to AIH decreased during the time intervals of the study. Compared to controls, cases were more likely men (40.0% vs. 18%, p = 0.049), with longer AIH duration (median 16 years vs. 5 years, p = 0.004). Prolonged AIH duration (OR 1.68, p = 0.006) and older age (OR 1.15, p = 0.049) were risk factors for HCC. Conclusions: AIH is a rare cause (1.6%) for HCC in Midwestern USA with a decreasing trend over 14.5 years. Ten percent of AIH-HCC patients did not have cirrhosis at time of HCC diagnosis. Patients with prolonged duration of the disease and older age are at high risk to develop HCC