269 research outputs found

    Energy Efficient Engine Low Pressure Subsystem Aerodynamic Analysis

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    The objective of this study was to demonstrate the capability to analyze the aerodynamic performance of the complete low pressure subsystem (LPS) of the Energy Efficient Engine (EEE). Detailed analyses were performed using three- dimensional Navier-Stokes numerical models employing advanced clustered processor computing platforms. The analysis evaluates the impact of steady aerodynamic interaction effects between the components of the LPS at design and off- design operating conditions. Mechanical coupling is provided by adjusting the rotational speed of common shaft-mounted components until a power balance is achieved. The Navier-Stokes modeling of the complete low pressure subsystem provides critical knowledge of component acro/mechanical interactions that previously were unknown to the designer until after hardware testing

    Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

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    Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

    Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis

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    Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression

    Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

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    Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

    IL4Rα signaling abrogates hypoxic neutrophil survival and limits acute lung injury responses <i>in vivo</i>

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    Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood.  Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1a (hypoxia-inducible factor-1a)mediated neutrophil adaptation, resulting in resolution of lung injury.  Methods: Neutrophil activation of IL4Ra (IL-4 receptor a) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4.  Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1a-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis.  Conclusions: We describe an important interaction whereby IL4Ra-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury

    Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payer database

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    Background: Appendectomy and colectomy are commonly performed surgical procedures. Despite evidence demonstrating advantages with the minimally invasive surgical (MIS) approach, open procedures occur with greater prevalence. Therefore, there is still controversy as to whether the MIS approach is safer or more cost effective. Methods: A retrospective analysis was performed using a large commercial payer database. The data included information on 7,532 appendectomies and 2,745 colectomies. Data on the distribution of patient demographic and comorbidity characteristics associated with the MIS and open approaches were reviewed. The corresponding complication rates and expenditures were analyzed. Summary statistics were compared using chi-square tests, and generalized linear models were constructed to estimate expenditures while controlling for patient characteristics. Results: The patients undergoing MIS and open colectomy showed no significant variations in age distribution or marginal age differences for appendectomy. Significantly more patients experienced an infection postoperatively, and procedure-specific complications were more common in the open group for both procedures (P < 0.05). The postsurgical hospital stay was longer for the patients treated using the open techniques, differing an average of half a day for appendectomies and significantly more (4 days) for colectomy (P < 0.05). Readmission rates differed little between the two approaches. Procedures performed through an MIS approach were associated with lower expenditures than for the open technique, with differences ranging from 700forappendectomypatients(P < 0.05)to700 for appendectomy patients (P < 0.05) to 15,200 for colectomy patients (P < 0.05). Conclusions: Minimally invasive appendectomy and colectomy were associated with lower infection rates, fewer complications, shorter hospital stays, and lower expenditures than open surgery

    Assessing and Refining Myocardial Infarction Risk Estimation Among Patients With Human Immunodeficiency Virus: A Study by the Centers for AIDS Research Network of Integrated Clinical Systems

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    Persons with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) have improved longevity but are at elevated risk for myocardial infarction (MI) due to common MI risk factors and HIV-specific factors. Despite these elevated MI rates, optimal methods to predict MI risks for HIV-infected persons remain unclear
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