136 research outputs found

    Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control

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    Sampled-data analysis and harmonic balance analysis are applied to analyze switching DC-DC converters under constant on-time control. Design-oriented boundary conditions for the period-doubling bifurcation and the saddle-node bifurcation are derived. The required ramp slope to avoid the bifurcations and the assigned pole locations associated with the ramp are also derived. The derived boundary conditions are more general and accurate than those recently obtained. Those recently obtained boundary conditions become special cases under the general modeling approach presented in this paper. Different analyses give different perspectives on the system dynamics and complement each other. Under the sampled-data analysis, the boundary conditions are expressed in terms of signal slopes and the ramp slope. Under the harmonic balance analysis, the boundary conditions are expressed in terms of signal harmonics. The derived boundary conditions are useful for a designer to design a converter to avoid the occurrence of the period-doubling bifurcation and the saddle-node bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications on August 10, 2011; Manuscript ID: CTA-11-016

    Fatigue-induced changes of impedance and performance in target tracking

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    Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability

    The Ethnomedicine of the Haya people of Bugabo ward, Kagera Region, north western Tanzania

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    \ud The Kagera region, in north western Tanzania, is endowed with a strong culture of traditional medicine that is well supported by a rich diversity of medicinal plants. However, most of the plants in this region have not been documented nor evaluated for safety and efficacy. As an initiative in that direction, this study documented the knowledge on medicinal plant use by traditional healers of Bugabo Ward in Bukoba District. Key informants were selected with the help of local government officials and information on their knowledge and use of plants for therapeutic purposes was gathered using a semi-structured interview format. In this study 94 plant species representing 84 genera and 43 families were found to be commonly used in the treatment of a variety of human ailments. The family Asteraceae had the highest number of species being used as traditional medicines. The study revealed that Malaria is treated using the highest number of different medicinal species (30), followed by skin conditions (19), maternal illnesses and sexually transmitted diseases (14), respiratory diseases (11) and yellow fever, Herpes simplex and peptic ulcers (10). Majority of the species are used to treat less than five different diseases/conditions each and leaves were the most commonly used part, comprising 40% of all the reports on use of plant parts. Trees comprised the most dominant growth form among all plants used for medicinal purposes in the study area. Bugabo Ward has a rich repository of medicinal plants and this reinforces the need for an extensive and comprehensive documentation of medicinal plants in the area and a concomitant evaluation of their biological activity as a basis for developing future medicines.\u

    Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6-24 months

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    <p>Abstract</p> <p>Background</p> <p>The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.</p> <p>The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months.</p> <p>Methods</p> <p>Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126].</p> <p>Results</p> <p>Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant.</p> <p>Conclusions</p> <p>Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study.</p> <p>Trial registration</p> <p>This study is registered with ClinicalTrials.gov, number .NCT00156832.</p

    Fluorescence-based high-throughput functional profiling of ligand-gated ion channels at the level of single cells

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    Ion channels are involved in many physiological processes and are attractive targets for therapeutic intervention. Their functional properties vary according to their subunit composition, which in turn varies in a developmental and tissue-specific manner and as a consequence of pathophysiological events. Understanding this diversity requires functional analysis of ion channel properties in large numbers of individual cells. Functional characterisation of ligand-gated channels involves quantitating agonist and drug dose-response relationships using electrophysiological or fluorescence-based techniques. Electrophysiology is limited by low throughput and high-throughput fluorescence-based functional evaluation generally does not enable the characterization of the functional properties of each individual cell. Here we describe a fluorescence-based assay that characterizes functional channel properties at single cell resolution in high throughput mode. It is based on progressive receptor activation and iterative fluorescence imaging and delivers >100 dose-responses in a single well of a 384-well plate, using α1-3 homomeric and αβ heteromeric glycine receptor (GlyR) chloride channels as a model system. We applied this assay with transiently transfected HEK293 cells co-expressing halide-sensitive yellow fluorescent protein and different GlyR subunit combinations. Glycine EC values of different GlyR isoforms were highly correlated with published electrophysiological data and confirm previously reported pharmacological profiles for the GlyR inhibitors, picrotoxin, strychnine and lindane. We show that inter and intra well variability is low and that clustering of functional phenotypes permits identification of drugs with subunit-specific pharmacological profiles. As this method dramatically improves the efficiency with which ion channel populations can be characterized in the context of cellular heterogeneity, it should facilitate systems-level analysis of ion channel properties in health and disease and the discovery of therapeutics to reverse pathological alterations

    Zinc or Multiple Micronutrient Supplementation to Reduce Diarrhea and Respiratory Disease in South African Children: A Randomized Controlled Trial

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    Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.Randomized, double-blind, controlled trial.Rural community in South Africa.THREE COHORTS: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.ClinicalTrials.gov NCT00156832

    High Extracellular Ca2+ Stimulates Ca2+-Activated Cl− Currents in Frog Parathyroid Cells through the Mediation of Arachidonic Acid Cascade

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    Elevation of extracellular Ca2+ concentration induces intracellular Ca2+ signaling in parathyroid cells. The response is due to stimulation of the phospholipase C/Ca2+ pathways, but the direct mechanism responsible for the rise of intracellular Ca2+ concentration has remained elusive. Here, we describe the electrophysiological property associated with intracellular Ca2+ signaling in frog parathyroid cells and show that Ca2+-activated Cl− channels are activated by intracellular Ca2+ increase through an inositol 1,4,5-trisphophate (IP3)-independent pathway. High extracellular Ca2+ induced an outwardly-rectifying conductance in a dose-dependent manner (EC50∼6 mM). The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed a deactivating inward tail current. Extracellular Ca2+-induced and Ca2+ dialysis-induced currents reversed at the equilibrium potential of Cl− and were inhibited by niflumic acid (a specific blocker of Ca2+-activated Cl− channel). Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca2+-induced current, suggesting the change of intracellular Cl− concentration in a few minutes. Extracellular Ca2+-induced currents displayed a moderate dependency on guanosine triphosphate (GTP). All blockers for phospholipase C, diacylglycerol (DAG) lipase, monoacylglycerol (MAG) lipase and lipoxygenase inhibited extracellular Ca2+-induced current. IP3 dialysis failed to induce conductance increase, but 2-arachidonoylglycerol (2-AG), arachidonic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HPETE) dialysis increased the conductance identical to extracellular Ca2+-induced conductance. These results indicate that high extracellular Ca2+ raises intracellular Ca2+ concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl− conductance
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