Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur

Pre-phase A study for an analysis of a reusable space tug. Volume 3 - Mission and operations analysis Final report

Mission model for operational and design requirements of space tug concept

The Space Physics Data System - Cosmic and Heliospheric Nodes

The Space Physics Data System (SPDS) is a community- driven network of information sources, linked and interfaced by World Wide Web software. The SPDS coordinators are community representatives to the NASA Space Physics Division, who are soliciting additional Web nodes, trying to keep the nodes organized, and soliciting information/suggestions about older data in danger of loss. Here we present a guide to data in Cosmic and Heliospheric nodes of the SPDS. New contributions to this system are being solicited and some funds may be available to assist with their development

Silicon Detector Studies with an Interferometric Thickness Mapper

A laser-interferometer system has been developed to precisely map the thickness variations of large-area silicon detectors. We describe the design and operation of the apparatus and the data processing carried out to derive thickness maps. We compare the results with a map made using accelerator beams of energetic heavy ions

A methodology for boost-glide transport technology planning

A systematic procedure is presented by which the relative economic value of technology factors affecting design, configuration, and operation of boost-glide transport can be evaluated. Use of the methodology results in identification of first-order economic gains potentially achievable by projected advances in each of the definable, hypersonic technologies. Starting with a baseline vehicle, the formulas, procedures and forms which are integral parts of this methodology are developed. A demonstration of the methodology is presented for one specific boost-glide system

Does directly observed therapy improve tuberculosis treatment? More evidence is needed to guide tuberculosis policy

Abstract Background Tuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only “supportive treatment supervision by treatment partners”, many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure. Discussion DOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma. To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide. Summary Rigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.http://deepblue.lib.umich.edu/bitstream/2027.42/134652/1/12879_2016_Article_1862.pd

Physical activity patterns across time-segmented youth sport flag football practice.

BACKGROUND: Youth sport (YS) reaches a large number of children world-wide and contributes substantially to children's daily physical activity (PA), yet less than half of YS time has been shown to be spent in moderate-to-vigorous physical activity (MVPA). Physical activity during practice is likely to vary depending on practice structure that changes across YS time, therefore the purpose of this study was 1) to describe the type and frequency of segments of time, defined by contextual characteristics of practice structure, during YS practices and 2) determine the influence of these segments on PA. METHODS: Research assistants video-recorded the full duration of 28 practices from 14 boys' flag football teams (2 practices/team) while children concurrently (N = 111, aged 5-11 years, mean 7.9 ± 1.2 years) wore ActiGraph GT1M accelerometers to measure PA. Observers divided videos of each practice into continuous context time segments (N = 204; mean-segments-per-practice = 7.3, SD = 2.5) using start/stop points defined by change in context characteristics, and assigned a value for task (e.g., management, gameplay, etc.), member arrangement (e.g., small group, whole group, etc.), and setting demand (i.e., fosters participation, fosters exclusion). Segments were then paired with accelerometer data. Data were analyzed using a multilevel model with segment as unit of analysis. RESULTS: Whole practices averaged 34 ± 2.4% of time spent in MVPA. Free-play (51.5 ± 5.5%), gameplay (53.6 ± 3.7%), and warm-up (53.9 ± 3.6%) segments had greater percentage of time (%time) in MVPA compared to fitness (36.8 ± 4.4%) segments (p ≤ .01). Greater %time was spent in MVPA during free-play segments compared to scrimmage (30.2 ± 4.6%), strategy (30.6 ± 3.2%), and sport-skill (31.6 ± 3.1%) segments (p ≤ .01), and in segments that fostered participation (36.1 ± 2.7%) than segments that fostered exclusion (29.1 ± 3.0%; p ≤ .01). Significantly greater %time was spent in low-energy stationary behavior in fitness (15.7 ± 3.4%) than gameplay (4.0 ± 2.9%) segments (p ≤ .01), and in sport-skill (17.6 ± 2.2%) than free-play (8.2 ± 4.2%), gameplay, and warm-up (10.6 ± 2.6%) segments (p < .05). CONCLUSIONS: The %time spent in low-energy stationary behavior and in MVPA differed by characteristics of task and setting demand of the segment. Restructuring the routine of YS practice to include segments conducive to MVPA could increase %time spent in MVPA during practice. As YS reaches a large number of children worldwide, increasing PA during YS has the potential to create a public health impact

THE POWER OF STRUCTURED DESIGNS AND MIXED MODELS IN A REAL WORLD EXPERIMENT

Justifications usually given for adopting an automated system pertain to a reduction in labor and an improvement in quality control. A manufacturer of a prototype instrument that automated some of the steps for culturing bacteria wanted to compare the automated system to the manual system. The manufacturer wanted to compare the two systems in 1) Total time needed to isolate the target bacteria, 2) Ability to isolate the target bacteria, 3) Amount of interference from background (non-target) bacterial growth, and 1) Extent of cross (sample to sample) contamination. This paper presents the experimental design used to make these comparisons and how the design helped discover some surprising results about laboratory quality control. The experiment presented illustrates the importance of a good experimental design, the power of current statistical tools, and that a thorough and appropriate analysis of a data set requires side-by-side good detective work by both statistician and client

Design Considerations for Efficient and Effective Microarray Studies

This paper describes the theoretical and practical issues in experimental design for gene expression microarrays. Specifically, this paper (1) discusses the basic principles of design (randomization, replication, and blocking) as they pertain to microarrays, and (2) provides some general guidelines for statisticians designing microarray studies

Nonuniversal behavior of scattering between fractional quantum Hall edges

Among the predicted properties of fractional quantum Hall states are fractionally charged quasiparticles and conducting edge-states described as chiral Luttinger liquids. In a system with a narrow constriction, tunneling of quasi-particles between states at different edges can lead to resistance and to shot noise. The ratio of the shot noise to the backscattered current, in the weak scattering regime, measures the fractional charge of the quasi-particle, which has been confirmed in several experiments. However, the non-linearity of the resistance predicted by the chiral Luttinger liquid theory was apparently not observed in some of these cases. As a possible explanation for these discrepancies, we consider a model where a smooth edge profile leads to formation of additional edge states. Coupling between the current carrying edge mode and the additional phonon like mode can lead to {\it nonuniversal} exponents in the current-voltage characteristic, while preserving the ratio between shot noise and the back-scattered current, for weak backscattering. For special values of the coupling, one may obtain a linear I-V behavior.Comment: 10 pages, 3 figure