246 research outputs found
Parallel Solver of Large Systems of Linear Inequalities Using Fourier-Motzkin Elimination
Fourier-Motzkin elimination is a computationally expensive but powerful method to solve a system of linear inequalities. These systems arise e.g. in execution order analysis for loop nests or in integer linear programming. This paper focuses on the analysis, design and implementation of a parallel solver for distributed memory for large systems of linear inequalities using the Fourier-Motzkin elimination algorithm. We also measure the speedup of parallel solver and prove that this implementation results in good scalability
Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA
Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 159 (2015): 156-166, doi:10.1016/j.aquatox.2014.12.017.Atlantic killifish (Fundulus heteroclitus) thrive in New Bedford Harbor (NBH), MA, highly contaminated with polychlorinated biphenyls (PCBs). Resident killifish have evolved tolerance to dioxin-like (DL) PCBs, whose toxic effects through the aryl hydrocarbon receptor (AhR) are well studied. In NBH, non-dioxin like PCBs (NDL PCBs), which lack activity toward the AhR, vastly exceed levels of DL congeners yet how killifish counter NDL toxic effects has not been explored. In mammals and fish, NDL PCBs are potent activators of ryanodine receptors (RyR), Ca2+ release channels necessary for a vast array of physiological processes. In the current study we compared the expression and function of RyR related pathways in NBH killifish with killifish from the reference site at Scorton Creek (SC, MA). Relative to the SC fish, adults from NBH displayed increased levels of skeletal muscle RyR1 protein, and increased levels of FK506-binding protein 12 kDa (FKBP12), an accessory protein essential for NDL PCB-triggered changes in RyR channel function. In accordance with increased RyR1 levels, NBH killifish displayed increased maximal ligand binding, increased maximal response to Ca2+ activation and increased maximal response to activation by the NDL PCB congener PCB 95. Compared to SC, NBH embryos and larvae had increased levels of mtor and ryr2 transcripts at multiple stages of development, and generations, while levels of serca2 were decreased at 9 days post-fertilization in the F1 and F2 generations. These findings suggest that there are compensatory and heritable changes in RyR mediated Ca2+ signaling proteins or potential signaling partners in NBH killifish.Funding was provided through the NIEHS Superfund Research Program
UC Davis (INP and EBF; P42-ES004699) and Boston University (JJS and JVG; P42-ES007381).
Support was supplied via the UC Davis NHLBI Training Grant (T32-HL086350, EBF). Additional support came from NIEHS 1R01-ES014901, 1R01-ES017425, the UC Davis Center for Children’s Environmental Health (1P01-ES011269, U.S. Environmental Protection Agency Grant 8354320), and an unrestricted JB Johnson Foundation gift grant.2015-12-1
Discovering transcriptional modules by Bayesian data integration
Motivation: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets.
Results: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs
Issues and Opportunities in Exotic Hadrons
The last few years have been witness to a proliferation of new results
concerning heavy exotic hadrons. Experimentally, many new signals have been
discovered that could be pointing towards the existence of tetraquarks,
pentaquarks, and other exotic configurations of quarks and gluons.
Theoretically, advances in lattice field theory techniques place us at the cusp
of understanding complex coupled-channel phenomena, modelling grows more
sophisticated, and effective field theories are being applied to an ever
greater range of situations. It is thus an opportune time to evaluate the
status of the field. In the following, a series of high priority experimental
and theoretical issues concerning heavy exotic hadrons is presented.Comment: White paper from INT workshop, "Modern Exotic Hadrons". References
added. Version to appear in Chinese Physics
Bayesian correlated clustering to integrate multiple datasets
Motivation: The integration of multiple datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct – but often complementary – information. We present a Bayesian method for the unsupervised integrative modelling of multiple datasets, which we refer to as MDI (Multiple Dataset Integration). MDI can integrate information from a wide range of different datasets and data types simultaneously (including the ability to model time series data explicitly using Gaussian processes). Each dataset is modelled using a Dirichlet-multinomial allocation (DMA) mixture model, with dependencies between these models captured via parameters that describe the agreement among the datasets.
Results: Using a set of 6 artificially constructed time series datasets, we show that MDI is able to integrate a significant number of datasets simultaneously, and that it successfully captures the underlying structural similarity between the datasets. We also analyse a variety of real S. cerevisiae datasets. In the 2-dataset case, we show that MDI’s performance is comparable to the present state of the art. We then move beyond the capabilities of current approaches and integrate gene expression, ChIP-chip and protein-protein interaction data, to identify a set of protein complexes for which genes are co-regulated during the cell cycle. Comparisons to other unsupervised data integration techniques – as well as to non-integrative approaches – demonstrate that MDI is very competitive, while also providing information that would be difficult or impossible to extract using other methods
Dose repartition in alveoli, alveolar ducts and bronchi of rats exposed to radon and its progeny, preliminary results
Recently, micronuclei scoring has been performed to estimate doses delivered to the lungs after heterogenous irradiation induced after inhalation of radon and its progeny. These studies were limited to the deep lung after either extraction of alveolar macrophages (AM) by lavage (Taya et al., 1994, Johnson and Newton, 1994) or enzymatic dissociation of lung cells to initiate fibroblast cultures (Khan et al., 1994). Dose estimates were performed after comparison with micronuclei formation induced in vitro by irradiation with alpha particles
Определение технических характеристик размешивания и проектирование оборудования для вязких сред
Существенным недостатком подходов у многих исследователей является большое количество упрощений расчетных моделей и невозможность точной количественной оценки параметров технологического процесса перемешивания. В данной работе, эффективность перемешивания трех видов импеллеров была исследована. Все расчеты и анализы были проведены с помощью не только физических моделей но и Ansys v17.2, что обеспечил качество результата данного исследования.In this study computational fluid dynamics (CFD) approach was used to study mixing in an Industrial tank. We use Ansys v17.2 to do the evaluation of fluid mixing efficiency. In this study we use three different mixer models to do the comparison. The objective was to analyze the extent of mixing in the tank by producing visual images of the various mixing zones in the tank domain
Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.
BACKGROUND/AIM
Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland.
PATIENTS AND METHODS
Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics.
RESULTS
Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy.
CONCLUSION
Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients
Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities
The first farmers from Central Europe reveal a genetic affinity to modern-day populations from the Near East and Anatolia, which suggests a significant demographic input from this area during the early Neolithic
- …