A numerical method is developed for coupling a multi-species kinetic plasma model with a 5N-moment multi-fluid plasma model. The simulation domain is decomposed such that the local conditions satisfy ...the corresponding plasma model's region of validity. The method allows for hybrid simulations by formulating each model as a set of conservation laws and using a continuum numerical method to solve each model's governing equations in the subdomains of the decomposed domain. The models are coupled through fluxes across subdomain interfaces. Two methods are explored for the formulation of the fluxes that can be self-consistently represented by both plasma models. One method allows for flux calculations consistent with the 5N-moment multi-fluid plasma model and assumes thermodynamic equilibrium within each species of the kinetic plasma model. The second method ensures conservation of the distribution function as well as mass, momentum, and energy by formulating the fluxes using a composite underlying distribution function at the subdomain interfaces. The methods are compared in 1D1V simulations of a double rarefaction wave and a plasma sheath using the WARPXM framework, which solves each model using the discontinuous Galerkin finite element method. Both methods for formulating the fluxes perform well as the subdomain interface distribution function approaches a Maxwellian, with the consistent method being more robust to larger deviations. A simulation of the magnetized Kelvin-Helmholtz instability in 2D2V is also performed using the consistent method, which demonstrates the potential of the domain-decomposed hybrid method in facilitating speedup and reduction in required computational resources for high-fidelity plasma simulations, allowing for the investigation of problems that are beyond current capabilities.
•A hybrid method coupling kinetic and fluid plasma models in simulation is presented.•Two approaches specifying discontinuous Galerkin numerical fluxes are shown.•Double rarefaction wave and plasma sheath tests are used to compare the approaches.•Magnetized Kelvin-Helmholtz instability simulations show the method's viability.
Abstract The FuZE sheared-flow-stabilized Z pinch at Zap Energy is simulated using whole-device modeling employing an axisymmetric resistive magnetohydrodynamic formulation implemented within the ...discontinuous Galerkin WARPXM framework. Simulations show formation of Z pinches with densities of approximately 10 22 m −3 and total DD fusion neutron rate of 10 7 per µ s for approximately 2 µ s. Simulation-derived synthetic diagnostics show peak currents and voltages within 10% and total yield within approximately 30% of experiment for similar plasma mass. The simulations provide insight into the plasma dynamics in the experiment and enable a predictive capability for exploring design changes on devices built at Zap Energy.
Farmer profit can be increased and air quality improved
Although intentional use of fires to transform land has decreased globally (
1
,
2
), particularly among highly capitalized countries through ...regulatory and market-oriented approaches and moral suasion, regulatory strategies have been less effective in southern and eastern Asia (see table S21). Some densely populated agricultural regions in China and India buck the global trend, showing increases in agricultural fires (
2
). This is particularly true in northwestern India, where rice residue burning makes a substantial contribution to air pollution and short-lived climate pollutants (
3
,
4
). Regulations are in place to reduce agricultural fires, but burning continues because of uncertainty regarding policy implementation and regarding access and returns to alternative technologies. With the field burning season soon upon us, we synthesize emerging evidence on alternatives to burning, clarify the business case for alternative practices, identify remaining uncertainties, and discuss approaches to increase their widespread adoption. Often, there are difficult trade-offs between environmental improvement and profitable economic opportunities. The case of crop residue management in northwestern India does not appear to fit this pattern and provides lessons that may be useful elsewhere.
BACKGROUND:The management of fistula-in-ano is a balance between fistula cure and preservation of continence.
OBJECTIVE:The aim of this study is to summarize the anal fistula plug literature for ...Crohnʼs and non-Crohnʼs fistula-in-ano in a homogenous patient population.
DATA SOURCES:PubMed, MEDLINE, Embase, and Cochrane medical databases were searched from 1995 to 2011. Abstracts from The American Society of Colon and Rectal Surgeons, The Society for Surgery of the Alimentary Tract, The European Society of Coloproctology, and the Association of Coloproctology of Great Britain and Ireland meetings between 2007 and 2010 were also evaluated.
STUDY SELECTION:Studies were included if results for patients with and without Crohnʼs disease could be differentiated. Patients with rectovaginal, anovaginal, rectourethral, or ileal-pouch vaginal fistulas were excluded as were studies where the mean or median follow-up was less than 3 months. Two researchers independently selected studies matching the inclusion criteria.
INTERVENTION:Anal fistula plug insertion was performed.
MAIN OUTCOME MEASURES:The primary outcomes measured were the overall fistula closure rates and length of follow-up.
RESULTS:Seventy-six articles or abstracts were identified from the title as being of relevance. Twenty studies (2 abstracts, 18 articles) were finally included. Study sample size ranged from 4 to 60 patients; 530 patients were included in all studies (488 non-Crohnʼs and 42 Crohnʼs patients). The plug extrusion rate was 8.7% (46 patients). The proportion of patients achieving fistula closure varied widely between studies for non-Crohnʼs, ranging from 0.2 (95% CI 0.04–0.48) to 0.86 (95% CI 0.64–0.97). The pooled proportion of patients achieving fistula closure in patients with non-Crohnʼs fistula-in-ano was 0.54 (95% CI 0.50–0.59). The proportion achieving closure in patients with Crohnʼs disease was similar (0.55, 95% CI 0.39–0.70).
LIMITATIONS:This study was limited by the variability of operative technique and perioperative care between studies.
CONCLUSIONS:Fistula closure is achieved by using the anal fistula plug in approximately 54% of patients without Crohnʼs disease. The anal fistula plug has not been adequately evaluated in the Crohnʼs population.
Identification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. ...Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics. Using a combination of high-throughput liquid-and-gas chromatography with mass spectrometry, we found 105 metabolites (
P
< 0.05) significantly altered at the chronic stage, indicating a robust alteration in the urine metabolite profile during disease. Assessment of altered metabolites against the Kyoto Encyclopedia of Genes and Genomes revealed distinct non-overlapping metabolic pathways and revealed phenylalanine-tyrosine and associated metabolism being the most impacted. Combined with previously performed plasma profiling, eight common metabolites were significantly altered in both of the biofluids. Metaboanalyst analysis of these common metabolites revealed that phenylalanine metabolism and Valine, leucine, and isoleucine biosynthetic pathways are central metabolic pathways in both bio-fluids and could be analyzed further, either for the discovery of therapeutics or biomarker development. Overall, our study suggests that urine and plasma metabolomics may contribute to the identification of a distinct metabolic fingerprint of EAE disease discriminating from the healthy control which may aid in the development of an objective non-invasive monitoring method for progressive autoimmune diseases like MS.
Graphical Abstract
Untargeted urinary metabolomics of a chronic mouse model of multiple sclerosis identified Phenylalanine, tyrosine & tryptophan metabolism as the significantly altered metabolic pathway. Eight common metabolites were identified when we combined urinary and plasma metabolic signature, which revealed a perturbation of Phenylalanine metabolism and valine, leucine & isoleucine metabolic pathways, involved in CNS dysfunction during diseases. The identified eight metabolic signature of urine and plasma may be of clinical relevance as potential biomarkers and guide towards the identification of specific metabolic pathways as novel drug targets.
Abstract Introduction While in vivo studies suggest poor survival of mesenchymal stromal cells (MSCs) after transplantation in ischemic conditions, in vitro studies report diverse effects on ...proliferation, apoptosis and differentiation of stem/precursor cells of different tissue-origin. The present focus is to understand the influence of ischemic microenvironment on the survival, proliferation, apoptosis, ROS-generation, antioxidant levels, immunophenotypic-expression and neurotrophic factor secretion of Wharton's Jelly (WJ)-MSCs. Method WJ-MSCs were cultured in normoxic and hypoxic conditions in presence and absence of serum and the end-point parameters were measured at 4 time-points. Cell survival, proliferation, apoptosis, ROS-generation and immunophenotypic-expression were quantitatively detected either by fluorimetry or flow cytometry techniques. ELISA-based methods were used for detection of antioxidant-substrate glutathione (GSH) and neurotrophic factors vascular endothelial factor (VEGF), hepatocyte growth factor (HGF) and brain-derived neurotrophic factor (BDNF). Expression of the antioxidants glutathione peroxidase (GPx) and superoxide dismutase 1 (SOD1), was measured by real-time RT-PCR. Result Immunophenotypic analysis showed reduction in mesenchymal-marker (CD73, CD90, and CD105) expression under ischemic conditions influenced mainly by hypoxia, whereas the decrease in cell-survival under ischemic condition was mainly as a result of nutrition depletion. This was associated with increased ROS-generation and apoptosis and reduction in antioxidants (GSH, GPx, SOD1). For neurotrophic factors, ELISA-readings showed that VEGF and HGF secretion (which were higher in hypoxia) peaked at 48 h and decreased from 72 h, though BDNF release did not decrease. Discussion Therapeutic benefits rendered by WJ-MSCs in in vitro ischemic microenvironment are highest at the 48 h time-point, declining thereafter with time probably due to failure in cellular defense systems and the onset of apoptosis. Conclusion It is hence clear that the growth factor deficiency is more lethal to the cells than hypoxia in ischemic microenvironment.
The genus
is a widespread pathogen that includes more than 30 Gram-negative species, many of which are opportunistic bacteria. Aeromonas species are naturally distributed in various aquatic sources. ...Infectious processes in marine animals such as fish usually develop under stressful conditions, and when their immune systems are weakened. MicroRNAs (miRNAs/miRs) are short, non-coding RNAs that post-transcriptionally regulate gene expression. Their diverse biological functions, such as influencing cell development, proliferation, differentiation, tumorigenesis, metabolism, and apoptosis have been studied in various animals. Fish is the most important source of aquatic nutrients throughout the world, and its market is constantly growing. Overpopulation in aquaculture brings infectious diseases that threaten the development of aquaculture around the world. There is extensive evidence that microRNAs are involved in modulating infectious processes and regulating the inflammatory response to major bacterial fish infections, including
. Here, we review the current literature on the fish microRNA repertoire and outline the physiological roles assigned to microRNAs to provide a foundation for future research during
infection. Understanding the interaction between microRNAs and
may provide clues to a remarkable strategy for preventing
infections in fish.
A recent genome-wide association study in a German population and two subsequent studies in European populations found that a non-synonymous single-nucleotide polymorphism (SNP), rs1049550, within ...the annexin A11 (ANXA11) gene was associated with susceptibility to sarcoidosis. We sought to identify additional ANXA11 variants independently associated with sarcoidosis, determine whether any sarcoidosis-associated ANXA11 variants were associated with chest radiographic phenotypes, and explore human leukocyte antigen (HLA) SNP-SNP interactions with ANXA11. A total of 209 SNPs spanning 100 kb including the 5' promoter, coding, and 3' untranslated regions of ANXA11 were genotyped for 1689 sarcoidosis cases and 1252 controls. After adjustment for rs1049550, two additional novel ANXA11 sarcoidosis associations were identified only in African Americans--rs61860052 (odds ratio (OR)=0.62; 95% confidence interval (CI)=0.40-0.97) and rs4377299 (OR=1.31; 95% CI=1.06-1.63). These associations were more pronounced in radiologically-classified Scadding stage IV sarcoidosis cases. We also identified a significant SNP-SNP interaction between rs1049550 and a sarcoidosis risk SNP (rs9268839) near the HLA-DRA locus. This further genetic dissection of ANXA11 may provide additional insight into the immune dysregulation characteristic of sarcoidosis pathophysiology.
Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multiorgan granulomatous inflammatory disease. African ancestry may influence disease pathogenesis, ...as African-Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1384 highly ancestry-informative single-nucleotide polymorphisms genotyped on 1357 sarcoidosis cases and 703 unaffected controls self-identified as African-American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)=1.90; P=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; P=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12, which had the most significant association with European ancestry (aRR=0.65; P=0.002), and markers on chromosomes 5p13 (aRR=1.46; P=0.005) and 5q31 (aRR=0.67; P=0.005), which correspond to regions we previously identified through sib-pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; P=2 × 10(-5)), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis.
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