45 research outputs found

    Parallel chemistry acceleration algorithm with ISAT table-size control in the application of gaseous detonation

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    In order to improve the computational efficiency of a parallel ISAT (in situ adaptive tabulation)-based chemistry acceleration algorithm in the computations of transient, chemically reacting flows, a control strategy is proposed to maintain the sizes of the data tables in the ISAT computations. The table-size control strategy is then combined with a parallel algorithm to simulate two-dimensional gaseous detonation wave propagation. In the computation of 2H2 + O2 detonation, two sets of tests are conducted to identify the size control strategy. In the first set, the maximum total table size (Mtot) summed over all sub-zones is fixed, while the maximum size of the table on each sub-zone (Msin) is varied. In the second set, a fixed Msin is used for all the tables on the sub-zones while Mtot is varied. A maximum speedup ratio of 4.29 is found in the former tests, while 5.52 is found in the latter. Two parameters, σf and p, are proposed to analyze the load balance and synchronization among table operations in the parallel ISAT computations in the above tests. It is found that both load balance and synchronization have clear influences on the speedup ratio. A parameter pM is defined, and a strategy to choose the optimal maximum table sizes (both Mtot and Msin) based on pM is proposed and is verified to be universal in the computations of both 2H2 + O2 detonation and C2H4 + 3O2 detonation. Finally, the parallel acceleration algorithm enhanced with table-size control is shown to be highly accurate for the detonations in both fuels

    MMTV-Wnt1 and -ΔN89β-Catenin Induce Canonical Signaling in Distinct Progenitors and Differentially Activate Hedgehog Signaling within Mammary Tumors

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    Canonical Wnt/β-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-ΔN89β-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin activate canonical Wnt signaling within distinct cell-types. ΔN89β-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18+ER−PR−CD24highCD49flow profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14+/p63+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-ΔN89β-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand

    Renal replacement therapy in acute kidney injury: controversy and consensus

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    Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future

    Genomics-assisted breeding in four major pulse crops of developing countries: present status and prospects

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    The global population is continuously increasing and is expected to reach nine billion by 2050. This huge population pressure will lead to severe shortage of food, natural resources and arable land. Such an alarming situation is most likely to arise in developing countries due to increase in the proportion of people suffering from protein and micronutrient malnutrition. Pulses being a primary and affordable source of proteins and minerals play a key role in alleviating the protein calorie malnutrition, micronutrient deficiencies and other undernourishment-related issues. Additionally, pulses are a vital source of livelihood generation for millions of resource-poor farmers practising agriculture in the semi-arid and sub-tropical regions. Limited success achieved through conventional breeding so far in most of the pulse crops will not be enough to feed the ever increasing population. In this context, genomics-assisted breeding (GAB) holds promise in enhancing the genetic gains. Though pulses have long been considered as orphan crops, recent advances in the area of pulse genomics are noteworthy, e.g. discovery of genome-wide genetic markers, high-throughput genotyping and sequencing platforms, high-density genetic linkage/QTL maps and, more importantly, the availability of whole-genome sequence. With genome sequence in hand, there is a great scope to apply genome-wide methods for trait mapping using association studies and to choose desirable genotypes via genomic selection. It is anticipated that GAB will speed up the progress of genetic improvement of pulses, leading to the rapid development of cultivars with higher yield, enhanced stress tolerance and wider adaptability

    Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

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    \ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p<0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

    Key signaling nodes in mammary gland development and cancer: β-catenin

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    β-Catenin plays important roles in mammary development and tumorigenesis through its functions in cell adhesion, signal transduction and regulation of cell-context-specific gene expression. Studies in mice have highlighted the critical role of β-catenin signaling for stem cell biology at multiple stages of mammary development. Deregulated β-catenin signaling disturbs stem and progenitor cell dynamics and induces mammary tumors in mice. Recent data showing deregulated β-catenin signaling in metaplastic and basal-type tumors suggest a similar link to reactivated developmental pathways and human breast cancer. The present review will discuss β-catenin as a central transducer of numerous signaling pathways and its role in mammary development and breast cancer

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    Not AvailableDescribes about the Anthrax disease in animalsNot Availabl

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    Not AvailableAnthrax, a zoonotic disease of global health security relevance, is primarily a fatal disease of herbivores animals. Pigs are moderately resistant to the infection; however, succumb to infection upon ingestion of heavily contaminated feed stuffs with Bacillus anthracis. In India, anthrax outbreaks occurring in domestic as well as wild animals have been reported from several states especially in Southern and Eastern regions. Globally as well as nationally, reports on anthrax incidences in pig rearing regions are limited. Nevertheless, with the advent of intensified integrated livestock farming practices at rural and peri-urban areas, there is a threat of zoonotic disease transmission to humans from animals in the lapse of bio-security measures at farm level. The current review highlights the risk of anthrax occurrence in pigs, etiology, mode of transmission, pathogenesis, clinical signs and various control measures.Not Availabl

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    Not AvailableSalmonella continues to be a major food safety and public health threat. In the present study, Salmonella enterica subsp. enterica serotypes Enteritidis (SE) and Typhimurium (ST) were isolated from poultry and characterized for virulence, antimicrobial susceptibility, and biofilm formation. Prevalence of Salmonella serotypes in poultry was 3.35%; predominant serotypes isolated were S. Enteritidis (68.1%) and S. Typhimurium (31.8%). Source‐wise, Salmonella were isolated from retail market chicken meat (4.8%), live chicken at farm (2.5%), and table eggs (2.1%). Salmonella isolates produced invA gene of 284 bp (100%), spvR gene of 310 bp (77.27%), spvC gene of 571 bp (22.72%), and stn gene of 260 bp (100%) as virulence/ pathogenicity determinants. Salmonella isolates exhibited resistance to common antimicrobials; 72.7% isolates showed multiple resistance (≥3 antimicrobial class), highest resistance was observed for polymyxin‐B (81.8%) followed by nalidixic acid (72.7%), colistin (59.1%), ampicillin/tetracyline (45.5%), ampicillin + sulbactam (40.9%), cefodroxil (18.2%), streptomycin (9.1%), and cefazidine/ceftriaxone‐tazobactam (4.5%). Multiple antimicrobial resistance (MAR) index of poultry Salmonella isolates ranged from 0.11 to 0.35; wherein, 59.1% isolates showed MAR of >0.2. About 81.8% Salmonella isolates produced biofilm and were categorized as strong (13.6%), moderate (45.4%), and weak (22.7%) biofilm producers. Occurrence of antimicrobial resistant virulent Salmonella strains in poultry requires implementation of suitable strategies so as to protect the public health.Not Availabl
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