186 research outputs found

    Combining polynomial chaos expansions and genetic algorithm for the coupling of electrophysiological models

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    The number of computational models in cardiac research has grown over the last decades. Every year new models with di erent assumptions appear in the literature dealing with di erences in interspecies cardiac properties. Generally, these new models update the physiological knowledge using new equations which reect better the molecular basis of process. New equations require the fi tting of parameters to previously known experimental data or even, in some cases, simulated data. This work studies and proposes a new method of parameter adjustment based on Polynomial Chaos and Genetic Algorithm to nd the best values for the parameters upon changes in the formulation of ionic channels. It minimizes the search space and the computational cost combining it with a Sensitivity Analysis. We use the analysis of di ferent models of L-type calcium channels to see that by reducing the number of parameters, the quality of the Genetic Algorithm dramatically improves. In addition, we test whether the use of the Polynomial Chaos Expansions improves the process of the Genetic Algorithm search. We conclude that it reduces the Genetic Algorithm execution in an order of 103 times in the case studied here, maintaining the quality of the results. We conclude that polynomial chaos expansions can improve and reduce the cost of parameter adjustment in the development of new models.Peer ReviewedPostprint (author's final draft

    Long range transport of soil dust and smoke pollution in the South Asian Region.

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    Transboundary transport of air pollution in the South Asian region has been an issue of increasing importance over the past several decades. Long–range transport of anthropogenic pollution is contrasted with that of pollution produced by natural processes such as dust storms or natural forest fires. Airborne particulate matter datasets covering the period from 2002 to 2007 from the neighboring countries like Bangladesh, India, Pakistan and Sri Lanka were used to find the source areas that are primarily responsible for long range transported pollutants. All four countries collected samples with the same type of sampler and follow the same technique for mass and BC measurements. It was found that high fine soil contributions were from dust storms. On the other hand, smoke in this region mainly comes from northern India where agricultural waste is often burned. © Elsevier B.V

    Can sacrificial feeding areas protect aquatic plants from herbivore grazing? Using behavioural ecology to inform wildlife management

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    Effective wildlife management is needed for conservation, economic and human well-being objectives. However, traditional population control methods are frequently ineffective, unpopular with stakeholders, may affect non-target species, and can be both expensive and impractical to implement. New methods which address these issues and offer effective wildlife management are required. We used an individual-based model to predict the efficacy of a sacrificial feeding area in preventing grazing damage by mute swans (Cygnus olor) to adjacent river vegetation of high conservation and economic value. The accuracy of model predictions was assessed by a comparison with observed field data, whilst prediction robustness was evaluated using a sensitivity analysis. We used repeated simulations to evaluate how the efficacy of the sacrificial feeding area was regulated by (i) food quantity, (ii) food quality, and (iii) the functional response of the forager. Our model gave accurate predictions of aquatic plant biomass, carrying capacity, swan mortality, swan foraging effort, and river use. Our model predicted that increased sacrificial feeding area food quantity and quality would prevent the depletion of aquatic plant biomass by swans. When the functional response for vegetation in the sacrificial feeding area was increased, the food quantity and quality in the sacrificial feeding area required to protect adjacent aquatic plants were reduced. Our study demonstrates how the insights of behavioural ecology can be used to inform wildlife management. The principles that underpin our model predictions are likely to be valid across a range of different resource-consumer interactions, emphasising the generality of our approach to the evaluation of strategies for resolving wildlife management problems

    Impact of COVID-19 on a Free Clinic Patient Population

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    The Robert R. Frank Student Run Free Clinic at WSUSOM, surveyed patients to determine the impact of the COVID-19 pandemic on its patient population. The study examined any challenges faced in food, financial status, transportation, and healthcare. A Qualtrics survey was administered with ethnicity, age, and gender as controls, while testing patient responses to social factors using the Likert scale. The survey was targeted to a portion of the clinic’s patient pool (n=33) over a span of three months and responses were analyzed using SPSS 26 regression analysis, ANOVA, and paired sample T-tests. Significant responses were across demographics, categories of impact, and pre/post COVID-19. Results show that access to fresh foods was severely impacted by COVID-19 (t = -3.19, p\u3c 0.05). Linear regression models show a correlation between difficulty accessing healthcare and medications, before and after COVID-19, indicating that the pandemic may have exacerbated pre-existing barriers to treatment (correlation = 0.810). Financial status has been the most affected with many patients indicating changes in employment or income status. 55% of the participants noted a greater use of savings or retirement money to make ends meet. A moderate correlation (0.471) was found between the use of public transportation prior to the pandemic and transportation barriers during the pandemic. We have decided to compile resources to address the needs based on the study results. Future research includes a longitudinal, follow-up survey to gauge any changes. Limitations include the study sample size and participation bias among the patient population

    The Relative Impact of Climate Change on the Extinction Risk of Tree Species in the Montane Tropical Andes.

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    There are widespread concerns that anthropogenic climate change will become a major cause of global biodiversity loss. However, the potential impact of climate change on the extinction risk of species remains poorly understood, particularly in comparison to other current threats. The objective of this research was to examine the relative impact of climate change on extinction risk of upper montane tree species in the tropical Andes, an area of high biodiversity value that is particularly vulnerable to climate change impacts. The extinction risk of 129 tree species endemic to the region was evaluated according to the IUCN Red List criteria, both with and without the potential impacts of climate change. Evaluations were supported by development of species distribution models, using three methods (generalized additive models, recursive partitioning, and support vector machines), all of which produced similarly high AUC values when averaged across all species evaluated (0.82, 0.86, and 0.88, respectively). Inclusion of climate change increased the risk of extinction of 18-20% of the tree species evaluated, depending on the climate scenario. The relative impact of climate change was further illustrated by calculating the Red List Index, an indicator that shows changes in the overall extinction risk of sets of species over time. A 15% decline in the Red List Index was obtained when climate change was included in this evaluation. While these results suggest that climate change represents a significant threat to tree species in the tropical Andes, they contradict previous suggestions that climate change will become the most important cause of biodiversity loss in coming decades. Conservation strategies should therefore focus on addressing the multiple threatening processes currently affecting biodiversity, rather than focusing primarily on potential climate change impacts

    PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila

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    Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL–mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance

    The Role of the Frank–Starling Law in the Transduction of Cellular Work to Whole Organ Pump Function: A Computational Modeling Analysis

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    We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain

    Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma

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    Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed.info:eu-repo/semantics/publishedVersio
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