15 research outputs found

    Diagnostic suite used for magnetohydrodynamics equilibrium reconstruction on the PEGASUS

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    This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder

    Temperature Control of Fimbriation Circuit Switch in Uropathogenic Escherichia coli: Quantitative Analysis via Automated Model Abstraction

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    Uropathogenic Escherichia coli (UPEC) represent the predominant cause of urinary tract infections (UTIs). A key UPEC molecular virulence mechanism is type 1 fimbriae, whose expression is controlled by the orientation of an invertible chromosomal DNA element—the fim switch. Temperature has been shown to act as a major regulator of fim switching behavior and is overall an important indicator as well as functional feature of many urologic diseases, including UPEC host-pathogen interaction dynamics. Given this panoptic physiological role of temperature during UTI progression and notable empirical challenges to its direct in vivo studies, in silico modeling of corresponding biochemical and biophysical mechanisms essential to UPEC pathogenicity may significantly aid our understanding of the underlying disease processes. However, rigorous computational analysis of biological systems, such as fim switch temperature control circuit, has hereto presented a notoriously demanding problem due to both the substantial complexity of the gene regulatory networks involved as well as their often characteristically discrete and stochastic dynamics. To address these issues, we have developed an approach that enables automated multiscale abstraction of biological system descriptions based on reaction kinetics. Implemented as a computational tool, this method has allowed us to efficiently analyze the modular organization and behavior of the E. coli fimbriation switch circuit at different temperature settings, thus facilitating new insights into this mode of UPEC molecular virulence regulation. In particular, our results suggest that, with respect to its role in shutting down fimbriae expression, the primary function of FimB recombinase may be to effect a controlled down-regulation (rather than increase) of the ON-to-OFF fim switching rate via temperature-dependent suppression of competing dynamics mediated by recombinase FimE. Our computational analysis further implies that this down-regulation mechanism could be particularly significant inside the host environment, thus potentially contributing further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs

    Design and noise model for CCD-based, time-resolved PHA measurements

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    This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder

    Rapid, Reproducible, Quantifiable NMR Metabolomics: Methanol and Methanol: Chloroform Precipitation for Removal of Macromolecules in Serum and Whole Blood

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    Background: Though blood is an excellent biofluid for metabolomics, proteins and lipids present in blood can interfere with 1d-1H NMR spectra and disrupt quantification of metabolites. Here, we present effective macromolecule removal strategies for serum and whole blood (WB) samples. Methods: A variety of macromolecule removal strategies were compared in both WB and serum, along with tests of ultrafiltration alone and in combination with precipitation methods. Results: In healthy human serum, methanol:chloroform:water extraction with ultrafiltration was compared to methanol precipitation with and without ultrafiltration. Methods were tested in healthy pooled human serum, and in serum from patients with sepsis. Effects of long-term storage at −80 °C were tested to explore the impact of macromolecule removal strategy on serum from different conditions. In WB a variety of extraction strategies were tested in two types of WB (from pigs and baboons) to examine the impact of macromolecule removal strategies on different samples. Conclusions: In healthy human serum methanol precipitation of serum with ultrafiltration was superior, but was similar in recovery and variance to methanol:chloroform:water extraction with ultrafiltration in pooled serum from patients with sepsis. In WB, high quality, quantifiable spectra were obtained with the use of a methanol: chloroform precipitation

    Implementation of an established algorithm and modifications for the identification of epilepsy patients in the veterans health administration

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    •Efforts for identifying epilepsy patients in the VHA are presented.•The number of epilepsy patients in the VHA ranges between 74,000 and 87,000.•Lessons learned would be helpful for future research after enactment of ICD −10. Identification of epilepsy patients from administrative data in large managed healthcare organizations is a challenging task. The objectives of this report are to describe the implementation of an established algorithm and different modifications for the estimation of epilepsy prevalence in the Veterans Health Administration (VHA). For the prevalence estimation during a given time period patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical encounters were identified. In contrast to the established algorithm, which required inclusion of diagnoses data from the time period of interest only, variants were tested by considering diagnoses data beyond prevalence period for improving sensitivity. One variant excluded data from diagnostic EEG and LTM clinics to improve specificity. Another modification also required documentation of seizures on the problem list (electronic list of patients’ established diagnoses). Of the variants tested, the one excluding information from diagnostic clinics and extending time beyond base period of interest for clinical encounters was determined to be superior. It can be inferred that the number of patients receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are needed for future prevalence estimation due to significant efforts presented. This review is not only beneficial for researchers interested in VHA related data but can also be helpful for managed healthcare organizations involved in epilepsy care aiming at accurate identification of patients from large administrative databases
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