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匹配条件: “ Peter Edward Joseph” ,找到相关结果约48582条。
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Adaptation of Endothelial Cells to Physiologically-Modeled, Variable Shear Stress
Joseph S. Uzarski, Edward W. Scott, Peter S. McFetridge
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057004
Abstract: Endothelial cell (EC) function is mediated by variable hemodynamic shear stress patterns at the vascular wall, where complex shear stress profiles directly correlate with blood flow conditions that vary temporally based on metabolic demand. The interactions of these more complex and variable shear fields with EC have not been represented in hemodynamic flow models. We hypothesized that EC exposed to pulsatile shear stress that changes in magnitude and duration, modeled directly from real-time physiological variations in heart rate, would elicit phenotypic changes as relevant to their critical roles in thrombosis, hemostasis, and inflammation. Here we designed a physiological flow (PF) model based on short-term temporal changes in blood flow observed in vivo and compared it to static culture and steady flow (SF) at a fixed pulse frequency of 1.3 Hz. Results show significant changes in gene regulation as a function of temporally variable flow, indicating a reduced wound phenotype more representative of quiescence. EC cultured under PF exhibited significantly higher endothelial nitric oxide synthase (eNOS) activity (PF: 176.0±11.9 nmol/105 EC; SF: 115.0±12.5 nmol/105 EC, p = 0.002) and lower TNF-a-induced HL-60 leukocyte adhesion (PF: 37±6 HL-60 cells/mm2; SF: 111±18 HL-60/mm2, p = 0.003) than cells cultured under SF which is consistent with a more quiescent anti-inflammatory and anti-thrombotic phenotype. In vitro models have become increasingly adept at mimicking natural physiology and in doing so have clarified the importance of both chemical and physical cues that drive cell function. These data illustrate that the variability in metabolic demand and subsequent changes in perfusion resulting in constantly variable shear stress plays a key role in EC function that has not previously been described.
Prediction of the Fragmentation Pathway of Atorvastatin De-Protonated Ion  [PDF]
Dev Kant Shandilya, Rekha Israni, Peter Edward Joseph
Open Access Library Journal (OALib Journal) , 2018, DOI: 10.4236/oalib.1104547
Abstract:
Introduction: A fragmentation pathway of atorvastatin de-protonated ion was proposed based on rational interpretation workflows. Method: The mass spectral data (MS, MS/MS and MS3) of atorvastatin was obtained by electrospray negative ionization mode with flow injection analysis; using liquid chromatography systems coupled with tandem mass spectrometers (Q-trap and Q-ToF). Results: The fragmentation pathway was established using fragment ions of de-protonated ion; elemental composition, molecular structure and mechanism of formation for each major fragment presented. Pathway was proposed based on the MS3 spectral data in combination with basic interpretation rules and rational workflows. Conclusion: This study and data interpretation workflows can be useful for writing fragmentation pathway, mechanism for formation of fragments, and can be applied for mass spectral data interpretation of similar small organic molecules.
Prediction of the Fragmentation Pathway of Valsartan Protonated Ion  [PDF]
Dev Kant Shandilya, Rekha Israni, Peter Edward Joseph
Open Access Library Journal (OALib Journal) , 2018, DOI: 10.4236/oalib.1104764
Abstract:
Introduction: A fragmentation pathway of valsartan protonated ion proposed based on rational interpretation workflows. Method: The mass spectral data (MS, MS/MS, and MS3) of valsartan protonated ion, were attained by electrospray positive ionization with flow injection analysis; using liquid chromatography systems hyphenated with hybrid tandem mass spectrometer (Q-trap). Results: The pathway of fragmentation was established using product ions of the protonated ion; elemental composition, molecular structure and mechanism of formation for significant product ions were proposed. A pathway was proposed based on the MS/MS and MS3 spectral data in combination with basic interpretation rules and rational workflows. Conclusion: Workflow used for data interpretation can be useful for writing the fragmentation pathway, a mechanism for the formation of fragments, and can be applied for mass spectral data interpretation of similar small organic molecules.
Real Time Systems with Nonpreemptive Priorities and Ample Maintenance Facilities  [PDF]
Joseph Kreimer, Edward Ianovsky
Journal of Computer and Communications (JCC) , 2015, DOI: 10.4236/jcc.2015.37004
Abstract: We consider a real time data acquisition and processing multiserver system with identical servers (such as unmanned aerial vehicles, machine controllers, overhearing devices, medical monitoring devices, etc.) which can be maintained/programmed for different kinds of activities (e.g. passive or active). This system provides a service for real time tasks arriving via several channels (such as surveillance regions, assembly lines, communication channels, etc.) and involves maintenance. We focus on the worst case analysis of the system with ample maintenance facilities exponentially distributed time to failure and maintenance times. We consider two kinds of models (with and without nonpreemptive priorities) and provide balance equations for steady state probabilities and various performance measures, when both operation and maintenance times are exponentially distributed.
Multiserver Multichannel Real-Time System with Limited Maintenance Facilities under Maximum Load  [PDF]
Edward Ianovsky, Joseph Kreimer
Open Journal of Applied Sciences (OJAppS) , 2015, DOI: 10.4236/ojapps.2015.57037
Abstract: We consider a multi server and multichannel real-time system with identical servers (e.g. unmanned aerial vehicles, machine controllers, etc.) that provide services for requests of real-time jobs arriving via several different channels (e.g. surveillance regions, assembly lines, etc.) working under maximum load regime. Each channel has its own constant numbers of jobs inside at any instant. Each channel has its own specifications, and therefore different kinds of equipment and inventory are needed to serve different channels. There is a limited number of identical maintenance teams (less than the total number of servers in the system). We compute analytically steady- state probabilities of this system, its availability, loss penalty function and other performance characteristics, when both service and maintenance times are exponentially distributed.
Prediction of the Fragmentation Pathway of Atorvastatin by Using High Resolution Collision Induced Dissociation (HR-MS/MS) Spectral Information  [PDF]
Dev Kant Shandilya, Rekha Israni, Peter Edward Joseph, Venkata Siva Satyanarayana Kantamreddi
Open Access Library Journal (OALib Journal) , 2017, DOI: 10.4236/oalib.1103473
Abstract:
Introduction: A possible fragmentation pathway of atorvastatin was proposed based on rational interpretation of high resolution collision induced dissociation (CID) fragmentation spectral data. Method: The mass spectral (MS and MS/MS) data of atorvastatin was obtained by using a flow injection analysis, LC coupled with high resolution mass analyzer system with Q-TOF technology. Results: The elemental composition for each major fragment was proposed with a calculated mass error in parts per million (ppm). The mass error found in this study is from 0.3 to 5.7 ppm; strongly supports all the proposed elemental composition of fragments. Based on the fragments, possible fragmentation pathway was proposed. Conclusion: The workflow followed for interpretation can also address the structural possibilities of similar type of small organic molecules.
Identification of Oxidative Degradation Products of Lansoprazole by Using High Resolution Mass Spectrometry Spectral Data  [PDF]
Dev Kant Shandilya, Rekha Israni, Peter Edward Joseph, Anoop Kumar, Manoj Pillai
International Journal of Analytical Mass Spectrometry and Chromatography (IJAMSC) , 2017, DOI: 10.4236/ijamsc.2017.53004
Abstract:
The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution mass spectrometer (HRMS) was used for identification of oxidative degradation impurities (DIs) of lansoprazole. The utilization of HRMS facilitates to determine the accurate mass of impurities and their fragment/product ions. A fast mass spectrometer (MS) compatible reverse phase chromatography method was used to investigate the oxidative stressed impurities. HPLC column; C18 (50 × 4.6 mm, 3.5 μm) was used with gradient elution. Spectral data acquired using information dependent acquisition (IDA) with real time dynamic background subtraction algorithm (DBS). Three oxidative impurities: DI-I (m/z 386.0781), DI-II (m/z 402.0734) and DI-III (m/z 386.0785), was observed during this study; interpretation of high resolution spectral data of all three impurities was carried out; elemental composition and molecular structure was proposed for major fragments. In this study mass error was found ≤7.7 parts per million (ppm).
Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection  [PDF]
Jonathan E. Schelfhout, Danijela A. Stojanovic, Amy Houtchens, Heidi M. Crane, Edward R. Cachay, Elizabeth R. Brown, Sonia M. Napravnik, Mari M. Kitahata, Michael S. Saag, Peter W. Hunt, Teresa L. Kauf, Joseph A. C. Delaney
World Journal of AIDS (WJA) , 2013, DOI: 10.4236/wja.2013.31006
Abstract:

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL; p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL; p-value < 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

The Effects of HIV on the Sensitivity of a Whole Blood IFN-γ Release Assay in Zambian Adults with Active Tuberculosis
Edward Raby, Maureen Moyo, Akash Devendra, Joseph Banda, Petra De Haas, Helen Ayles, Peter Godfrey-Faussett
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002489
Abstract: Background Interferon gamma release assays (IGRA) are replacing the tuberculin skin test (TST) as a diagnostic tool for Mycobacterium tuberculosis infection. However research into the test's performance in the high HIV-TB burden setting is scarce. This study aimed to define the sensitivity of an IGRA, QuantiFERON-TB? Gold In-Tube (QGIT), in adult Zambian patients with active smear-positive tuberculosis. Secondary outcomes focussed on the effect of HIV on the test's performance. Principal Findings Patients attending government health clinics were recruited within 1 month of starting treatment for TB. Subjects were tested with QGIT and TST. T lymphocyte counts were estimated (CD3+, CD4+, CD8+). QGIT was performed for 112 subjects. 83/112 were QGIT positive giving an overall sensitivity of 74% [95%CI: 66,82]. A marked decrease in sensitivity was observed in HIV positive patients with 37/59 (63%) being QGIT positive compared to 31/37 (84%) HIV negative patients [chi2 p = 0.033]. Low CD4+ count was associated with increases in both indeterminate and false-negative results. Low CD4+ count in combination with high/normal CD8+ count was associated with false-negative results. TST was recorded for 92 patients, 62/92 were positive, giving a sensitivity of 67% [95%CI: 58,77]. Although there was little difference in the overall sensitivities, agreement between TST and QGIT was poor. Conclusions QGIT was technically feasible with results in HIV negative subjects comparable to those achieved elsewhere. However, where under-treated HIV is prevalent, an increased proportion of both indeterminate and false-negative QGIT results can be expected in patients with active TB. The implications of this for the diagnosis of LTBI by QGIT is unclear. The diagnostic and prognostic relevance of IGRAs in high burden settings needs to be better characterised.
Impact of insecticide-treated bed nets on malaria transmission indices on the south coast of Kenya
Francis M Mutuku, Charles H King, Peter Mungai, Charles Mbogo, Joseph Mwangangi, Eric M Muchiri, Edward D Walker, Uriel Kitron
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-356
Abstract: To evaluate the impact of the substantial increase in household bed net use within this area on vector density, vector composition, and human-vector contact, indoor and outdoor resting mosquitoes were collected in the same region during 2009-2010 using pyrethrum spray catches and clay pots for indoor and outdoor collections respectively. Information on bed net use per sleeping spaces and factors influencing mosquito density were determined in the same houses using Poisson regression analysis. Species distribution was determined, and number of mosquitoes per house, human-biting rates (HBR), and entomological inoculation rate (EIR) were compared to those reported for the same area during 1997-1998, when bed net coverage had been minimal.Compared to 1997-1998, a significant decline in the relative proportion of An. gambiae s.s. among collected mosquitoes was noted, coupled with a proportionate increase of An. arabiensis. Following > 5 years of 60-86% coverage with bed nets, the density, human biting rate and EIR of indoor resting mosquitoes were reduced by more than 92% for An. funestus and by 75% for An. gambiae s.l. In addition, the host feeding choice of both vectors shifted more toward non-human vertebrates. Besides bed net use, malaria vector abundance was also influenced by type of house construction and according to whether one sleeps on a bed or a mat (both of these are associated with household wealth). Mosquito density was positively associated with presence of domestic animals.These entomological indices indicate a much reduced human biting rate and a diminishing role of An. gambiae s.s. in malaria transmission following high bed net coverage. While increasing bed net coverage beyond the current levels may not significantly reduce the transmission potential of An. arabiensis, it is anticipated that increasing or at least sustaining high bed net coverage will result in a diminished role for An. funestus in malaria transmission.Many studies have reported the k
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