The effect of prostaglandin E2 on cystine uptake and glutathione synthesis by human lung fibroblasts

AbstractProstaglandin E2 (PGE2) is an inflammatory mediator capable of regulating fibroblast cell proliferation, matrix protein production, and system A amino acid transport. System x−c amino acid transport is regulated by electrophilic agents and oxygen. The effect of PGE2 on the x−c system transport of cystine and the synthesis of glutathione by human lung fibroblasts was examined. Preincubation of fibroblast cultures with PGE2 decreased cystine uptake by 42%. Kinetic studies revealed a 42% decrease in the Vmax of the x−c system transporter in PGE2-treated fibroblasts; however, the apparent Km was not affected. The glutathione content of PGE2-treated fibroblasts was decreased by up to 25% of control. These results demonstrate that system x−c transport of cystine is regulated by PGE2 and suggest that the limited availability of intracellular cysteine inhibited glutathione synthesis

Magnetic field waves at Uranus

The proposed research efforts funded by the UDAP grant to the BRI involve the study of magnetic field waves associated with the Uranian bow shock. This is a collaborative venture bringing together investigators at the BRI, Southwest Research Institute (SwRI), and Goddard Space Flight Center (GSFC). In addition, other collaborations have been formed with investigators granted UDAP funds for similar studies and with investigators affiliated with other Voyager experiments. These investigations and the corresponding collaborations are included in the report. The proposed effort as originally conceived included an examination of waves downstream from the shock within the magnetosheath. However, the observations of unexpected complexity and diversity within the upstream region have necessitated that we confine our efforts to those observations recorded upstream of the bow shock on the inbound and outbound legs of the encounter by the Voyager 2 spacecraft

Biogenic 2‐methyl‐3‐buten‐2‐ol increases regional ozone and HO x sources

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95042/1/grl23505.pd

Magnetic field waves at Uranus

The research efforts funded by the Uranus Data Analysis Program (UDAP) grant to the Bartol Research Institute (BRI) involved the study of magnetic field waves associated with the Uranian bow shock. Upstream wave studies are motivated as a study of the physics of collisionless shocks. Collisionless shocks in plasmas are capable of 'reflecting' a fraction of the incoming thermal particle distribution and directing the resulting energetic particle motion back into the upstream region. Once within the upstream region, the backward streaming energetic particles convey information of the approaching shock to the supersonic flow. This particle population is responsible for the generation of upstream magnetic and electrostatic fluctuations known as 'upstream waves', for slowing the incoming wind prior to the formation of the shock ramp, and for heating of the upstream plasma. The waves produced at Uranus not only differed in several regards from the observations at other planetary bow shocks, but also gave new information regarding the nature of the reflected particle populations which were largely unmeasurable by the particle instruments. Four distinct magnetic field wave types were observed upstream of the Uranian bow shock: low-frequency Alfven or fast magnetosonic waves excited by energetic protons originating at or behind the bow shock; whistler wave bursts driven by gyrating ion distributions within the shock ramp; and two whistler wave types simultaneously observed upstream of the flanks of the shock and argued to arise from resonance with energetic electrons. In addition, observations of energetic particle distributions by the LECP experiment, thermal particle populations observed by the PLS experiment, and electron plasma oscillations recorded by the PWS experiment proved instrumental to this study and are included to some degree in the papers and presentations supported by this grant

Granite disposal of U.S. high-level radioactive waste.

This report evaluates the feasibility of disposing U.S. high-level radioactive waste in granite several hundred meters below the surface of the earth. The U.S. has many granite formations with positive attributes for permanent disposal. Similar crystalline formations have been extensively studied by international programs, two of which, in Sweden and Finland, are the host rocks of submitted or imminent repository license applications. This report is enabled by the advanced work of the international community to establish functional and operational requirements for disposal of a range of waste forms in granite media. In this report we develop scoping performance analyses, based on the applicable features, events, and processes (FEPs) identified by international investigators, to support generic conclusions regarding post-closure safety. Unlike the safety analyses for disposal in salt, shale/clay, or deep boreholes, the safety analysis for a mined granite repository depends largely on waste package preservation. In crystalline rock, waste packages are preserved by the high mechanical stability of the excavations, the diffusive barrier of the buffer, and favorable chemical conditions. The buffer is preserved by low groundwater fluxes, favorable chemical conditions, backfill, and the rigid confines of the host rock. An added advantage of a mined granite repository is that waste packages would be fairly easy to retrieve, should retrievability be an important objective. The results of the safety analyses performed in this study are consistent with the results of comprehensive safety assessments performed for sites in Sweden, Finland, and Canada. They indicate that a granite repository would satisfy established safety criteria and suggest that a small number of FEPs would largely control the release and transport of radionuclides. In the event the U.S. decides to pursue a potential repository in granite, a detailed evaluation of these FEPs would be needed to inform site selection and safety assessment

Study design and rationale for investigating phosphodiesterase type 5 inhibition for the treatment of pulmonary hypertension due to chronic obstructive lung disease: the TADA-PHiLD (TADAlafil for Pulmonary Hypertension associated with chronic obstructive Lung Disease) trial

Abstract In patients with chronic obstructive pulmonary disease (COPD), moderate or severe pulmonary hypertension (COPD-PH) is associated with increased rates of morbidity and mortality. Despite this, approaches to treatment and the efficacy of phosphodiesterase type 5 inhibition (PDE-5i) in COPD-PH are unresolved. We present the clinical rationale and study design to assess the effect of oral tadalafil on exercise capacity, cardiopulmonary hemodynamics, and clinical outcome measures in COPD-PH patients. Male and female patients 40–85 years old with GOLD stage 2 COPD or higher and pulmonary hypertension diagnosed on the basis of invasive cardiac hemodynamic assessment (mean pulmonary artery pressure [mPAP] >30 mmHg, pulmonary vascular resistance [PVR] >2.5 Wood units, and pulmonary capillary wedge pressure ≤18 mmHg at rest) will be randomized at a 1∶1 ratio to receive placebo or oral PDE-5i with tadalafil (40 mg daily for 12 months). The primary end point is change from baseline in 6-minute walk distance at 12 months. The secondary end points are change from baseline in PVR and mPAP at 6 months and change from baseline in peak volume of oxygen consumption () during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (Sao2) at rest and during exercise will function as safety outcome measures. TADA-PHiLD (TADAlafil for Pulmonary Hypertension assocIated with chronic obstructive Lung Disease) is the first sufficiently powered randomized clinical trial testing the effect of PDE-5i on key clinical and drug safety outcome measures in patients with at least moderate PH due to COPD

Analysis of continuously rotating quadrupole focusing channels using generalized Courant-Snyder theory

By extending the recently developed generalized Courant-Snyder theory for coupled transverse beam dynamics, we have constructed the Gaussian beam distribution and its projections with arbitrary mode emittance ratios. The new formulation has been applied to a continuously rotating quadrupole focusing channel because the basic properties of this channel are known theoretically and could also be investigated experimentally in a compact setup such as the linear Paul trap configuration. The new formulation retains a remarkably similar mathematical structure to the original Courant-Snyder theory, and thus, provides a powerful theoretical tool to investigate coupled transverse beam dynamics in general and more complex linear focusing channels.close

Emisari: a management information system designed to aid and involve people

The EMISARI System described in this paper represents a major departure from conventional MIS design. It is oriented not toward data per se, but rather toward activities of the people who generate and use the data. Thus it provides not merely for reporting up the chain of command, but also for dissemination of policy guidance and reference material down the chain, and for lateral communication among all users. It places a premium upon flexibility, to permit rapid system modifications in response to changes in user functions and needs and it offers a greatly simplified operation, to avoid any necessity for extensive user training or complex operation manuals. The overall approach may be viewed as a greatly modernized version of the classic telephone party line, using a computer to organize, selectively sort, and store-and-forward a constant flow of statistics, messages, estimates, reference materials, guidelines, notices, and other informational accountrements of a modern management operation

Profiling quality of care for patients with chronic headache in three different German hospitals – a case study

BACKGROUND: Legal requirements for quality assurance in German rehabilitation hospitals include comparisons of providers. Objective is to describe and to compare outcome quality of care offered by three hospitals providing in-patient rehabilitative treatment exemplified for patients with chronic headache. METHODS: We performed a prospective three center observational study on patients suffering from chronic headache. Patients underwent interventions commonly used according to internal guidelines of the hospitals. Measurements were taken at three points in time (at admission, at discharge and 6 months after discharge). Indicators of outcome quality included pain intensity and frequency of pain, functional ability, depression, quality of life and health related behavior. Analyses of differences amongst the hospitals were adjusted by covariates due to case-mix situation. RESULTS: 306 patients from 3 hospitals were included in statistical analysis. Amongst the hospitals, patients differed significantly in age, education, diagnostic subgroups, beliefs, and with respect to some pain-related baseline values (covariates). Patients in all three hospitals benefited from intervention to a clinically relevant degree. At discharge from hospital, outcome quality differed significantly after adjustment according to case-mix only in terms of patients' global assessment of treatment results. Six months after discharge, the only detectable significant differences were for secondary outcomes like improved coping with stress or increased use of self-help. The profiles for satisfaction with the hospital stay showed clear differences amongst patients. CONCLUSION: The results of this case study do not suggest a definite overall ranking of the three hospitals that were compared, but outcome profiles offer a multilayer platform of reliable information which might facilitate decision making