35 research outputs found

    Paradoxical Role of Prion Protein Aggregates in Redox-Iron Induced Toxicity

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    Imbalance of iron homeostasis has been reported in sporadic Creutzfeldt-Jakob-disease (sCJD) affected human and scrapie infected animal brains, but the contribution of this phenotype to disease associated neurotoxicity is unclear.Using cell models of familial prion disorders, we demonstrate that exposure of cells expressing normal prion protein (PrP(C)) or mutant PrP forms to a source of redox-iron induces aggregation of PrP(C) and specific mutant PrP forms. Initially this response is cytoprotective, but becomes increasingly toxic with time due to accumulation of PrP-ferritin aggregates. Mutant PrP forms that do not aggregate are not cytoprotective, and cells show signs of acute toxicity. Intracellular PrP-ferritin aggregates induce the expression of LC3-II, indicating stimulation of autophagy in these cells. Similar observations are noted in sCJD and scrapie infected hamster brains, lending credence to these results. Furthermore, phagocytosis of PrP-ferritin aggregates by astrocytes is cytoprotective, while culture in astrocyte conditioned medium (CM) shows no measurable effect. Exposure to H(2)O(2), on the other hand, does not cause aggregation of PrP, and cells show acute toxicity that is alleviated by CM.These observations suggest that aggregation of PrP in response to redox-iron is cytoprotective. However, subsequent co-aggregation of PrP with ferritin induces intracellular toxicity unless the aggregates are degraded by autophagosomes or phagocytosed by adjacent scavenger cells. H(2)O(2), on the other hand, does not cause aggregation of PrP, and induces toxicity through extra-cellular free radicals. Together with previous observations demonstrating imbalance of iron homeostasis in prion disease affected brains, these observations provide insight into the mechanism of neurotoxicity by redox-iron, and the role of PrP in this process

    Конструкція контролера нечіткої логіки для управління напругою, частотою, струмом та потужністю ізольованої мікромережі на основі трифазної розподіленої генерації

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    Сьогоднішні екологічно чисті технології, пов'язані з мікромережами, наближаються до розумної системи наномереж. Вона задовольняє попит на електроенергію у всьому світі шляхом належного використання відновлюваних джерел енергії та систем накопичення енергії. Проте, управління електростанцією з використанням мікромереж перейшло на рівень, який вимагає складного і плавного контролю у взаємодії з мережею, включаючи розподілену операцію ізоляції. Динаміка навантаження і похибки є загальними проблемами, що впливають на профіль частоти, напруги та потужності мікромережі, яка є відповідальною за пошкодження навантаження та системи енергопостачання. У статті запропоновано конструкцію надійного контролера нечіткої логіки (FLC) для регулювання характеристик трифазної ізольованої мікромережі. Характеристики запропонованого FLC досліджували за різних умов навантаження, надійність яких оцінювали у стані несправності. Досліджувані характеристики мікромережі забезпечують високе відстеження та надійну роботу запропонованого FLC.Today’s clean technologies related to microgrids are approaching towards the smart nanogrid system. It fulfils the demand of the electricity throughout the world by proper using of renewable energy sources and energy storage systems. Still, the microgrid (MG) power plant control has enriched to a level that it will require complicated and smooth control in the grid interaction including distributed islanding operation. The load dynamics and uncertainties are the common issues which hampers the frequency, voltage and power profile of the MG that is responsible to damage the load and power system. The design of robust fuzzy logic controller (FLC) has been proposed in this research article to regulate the performances of three-phase islanded MG. The performance of the proposed FLC has been examined under different loading condition whose robustness has been evaluated under faulty condition. The investigated performances of the MG ensure high tracking and robust performance of the proposed FLC

    Predicting maximal oxygen uptake from the 6 min walk test in patients with heart failure

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    Aims A cardiopulmonary exercise (CPX) test is considered the gold standard in evaluating maximal oxygen uptake. This study aimed to evaluate the predictive validity of equations provided by Burr et al., Ross et al., Adedoyin et al., and Cahalin et al. in predicting peak VO2 from 6 min walk test (6MWT) distance in patients with heart failure (HF). Methods and Results New York Heart Association Class I-III HF patients performed a maximal effort CPX test and two 6MWTs. Correlations between CPX VO2 peak and the predicted VO2 peak, coefficient of determination (R-2), and mean absolute percentage error (MAPE) scores were calculated. P-values were set at 0.05. A total of 106 participants aged 62.5 +/- 11.5 years completed the tests. The mean VO2 peak from CPX testing was 16.4 +/- 3.9 mL/kg/min, and the mean 6MWT distance was 419.2 +/- 93.0 m. The predicted mean VO2 peak (mL/kg/min) by Burr et al., Ross et al., Adedoyin et al., and Cahalin et al. was 22.8 +/- 8.8, 14.6 +/- 2.1, 8.30 +/- 1.4, and 16.6 +/- 2.8. A significant correlation was observed between the CPX test VO2 peak and predicted values. The mean difference (0.1 mL/kg/min), R-2 (0.97), and MAPE (0.14) values suggest that the Cahalin et al. equation provided the best predictive validity. Conclusions The equation provided by Cahalin et al. is simple and has a strong predictive validity, and researchers may use the equation to predict mean VO2 peak in patients with HF. Based on our observation, equations to predict individual maximal oxygen uptake should be used cautiously.Funding Agencies|NHLBI of the National Institutes of HealthUnited States Department of Health &amp; Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung &amp; Blood Institute (NHLBI) [R01HL112979]</p

    Wireless innovation through software radios

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    A research agenda for malaria eradication: drugs.

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    Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission
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