461 research outputs found

    Wybrane uwarunkowania i problemy związane z prowadzeniem konkursów jakości opartych na modelu doskonałości na szczeblu lokalnym – studium przypadku

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    The aim of this article was to present characteristic phenomena accompanying competitions for quality awards based on the use of the organizational excellence models implemented at the regional level. Typical problems were identifid, the understanding of which allows for a better use of the idea of excellence to raise the overall level of maturity of organizations aspiring to quality awards at every level. The results of self-assessment and external verifiation of organizations participating in the 21st edition of the Competition for the Pomeranian Quality Award were presented. On the basis of in-depth interviews with employees of the competition organizing unit as well as source materials, a diagnosis of the current state concerning this undertaking was presented and some directions of improvement actions were defied.Celem autorów było przedstawienie charakterystycznych zjawisk towarzyszących konkursom o nagrody jakości, opierających się na zastosowaniu modeli doskonałości organizacyjnej, realizowanych na szczeblu regionalnym. Wskazano typowe problemy, których zrozumienie umożliwia lepiej wykorzystać ideę doskonałości do podniesienia ogólnego poziomu dojrzałości organizacji aspirujących do nagród jakości na każdym szczeblu. Przedstawiono wyniki samooceny i zewnętrznej weryfiacji organizacji biorących udział w 21 edycji Konkursu o Pomorską Nagrodę Jakości. Na podstawie wywiadów pogłębionych, przeprowadzonych z pracownikami jednostki organizującej konkurs, a także materiałów źródłowych, opracowano diagnozę stanu aktualnego dotyczącą tego przedsięwzięcia oraz określono niektóre kierunki działań doskonalących

    Regulation of Pancreatic Beta Cell Stimulus-Secretion Coupling by microRNAs.

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    Increased blood glucose after a meal is countered by the subsequent increased release of the hypoglycemic hormone insulin from the pancreatic beta cells. The cascade of molecular events encompassing the initial sensing and transport of glucose into the beta cell, culminating with the exocytosis of the insulin large dense core granules (LDCVs) is termed "stimulus-secretion coupling." Impairment in any of the relevant processes leads to insufficient insulin release, which contributes to the development of type 2 diabetes (T2D). The fate of the beta cell, when exposed to environmental triggers of the disease, is determined by the possibility to adapt to the new situation by regulation of gene expression. As established factors of post-transcriptional regulation, microRNAs (miRNAs) are well-recognized mediators of beta cell plasticity and adaptation. Here, we put focus on the importance of comprehending the transcriptional regulation of miRNAs, and how miRNAs are implicated in stimulus-secretion coupling, specifically those influencing the late stages of insulin secretion. We suggest that efficient beta cell adaptation requires an optimal balance between transcriptional regulation of miRNAs themselves, and miRNA-dependent gene regulation. The increased knowledge of the beta cell transcriptional network inclusive of non-coding RNAs such as miRNAs is essential in identifying novel targets for the treatment of T2D

    Protein Phosphatase 1 (PP1) Is a Post-Translational Regulator of the Mammalian Circadian Clock

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    Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock

    A pathway-driven predictive model of tramadol pharmacogenetics

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    Predicting metabolizer phenotype (MP) is typically performed using data from a single gene. Cytochrome p450 family 2 subfamily D polypeptide 6 (CYP2D6) is considered the primary gene for predicting MP in reference to approximately 30% of marketed drugs and endogenous toxins. CYP2D6 predictions have proven clinically effective but also have well-documented inaccuracies due to relatively high genotype-phenotype discordance in certain populations. Herein, a pathway-driven predictive model employs genetic data from uridine diphosphate glucuronosyltransferase, family 1, polypeptide B7 (UGT2B7), adenosine triphosphate (ATP)-binding cassette, subfamily B, number 1 (ABCB1), opioid receptor mu 1 (OPRM1), and catechol-O-methyltransferase (COMT) to predict the tramadol to primary metabolite ratio (T:M1) and the resulting toxicologically inferred MP (t-MP). These data were then combined with CYP2D6 data to evaluate performance of a fully combinatorial model relative to CYP2D6 alone. These data identify UGT2B7 as a potentially significant explanatory marker for T:M1 variability in a population of tramadol-exposed individuals of Finnish ancestry. Supervised machine learning and feature selection were used to demonstrate that a set of 16 loci from 5 genes can predict t-MP with over 90% accuracy, depending on t-MP category and algorithm, which was significantly greater than predictions made by CYP2D6 alone.Peer reviewe

    Food and Agricultural Approaches to Reducing Malnutrition (FAARM): protocol for a cluster-randomised controlled trial to evaluate the impact of a Homestead Food Production programme on undernutrition in rural Bangladesh

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    IntroductionChronic undernutrition affects over 150 million children worldwide and has serious consequences. The causes are complex and include insufficient dietary diversity and poor hygiene practices. Systematic reviews of nutrition-sensitive agricultural interventions concluded that while these hold promise, there is insufficient evidence for their impact on child growth. The Food and Agricultural Approaches to Reducing Malnutrition (FAARM) project is a 1:1 cluster-randomised trial aiming to evaluate the impact of a Homestead Food Production (HFP) programme implemented by Helen Keller International on women’s and children’s undernutrition.Methods and analysisThe HFP intervention comprises training of women’s groups and asset distribution to support year-round home gardening, poultry rearing and improved nutrition and hygiene practices. Formal trainings are supplemented by behaviour change communication during household visits, and facilitated links between producer groups and market actors. The FAARM trial will examine if and how this complex intervention reduces undernutrition. In 2015, FAARM enrolled married women and their children (0–3 years) in 96 rural settlements of Habiganj district in Sylhet division, Bangladesh. Covariate-constrained randomisation was used to assign 48 settlements to receive a 3-year HFP intervention, with the other 48 acting as controls, targeting over 2700 women. To study impact pathways, a surveillance system collects data on all participants every 2 months. In late 2019, children 0–3 years of age (born during the intervention period) will be surveyed, thus capturing impact during the critical first 1000 days of life. Children’s length/height-for-age z-scores will be compared between intervention and control arms using mixed-effects linear regression. Secondary outcomes include women’s and children’s micronutrient status, dietary intake, dietary diversity and other indicators of child growth, development and morbidity.Ethics and disseminationEthical approval was received in Bangladesh and Germany. Results will be disseminated through peer-reviewed publications and presentations in Bangladesh and internationally.Trial registration numberNCT02505711; Pre-results.</jats:sec

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    Natural potential for tourism development in Southern Altai (Kazakhstan)

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    The mountain regions incorporate some of the major ecosystems of the Earth. They also include most significant mineral, natural, agricultural and tourist-recreational resources. A complex regionally-specific geographic evaluation is prerequisite for assessment of a perspective tourism development in a particular mountain area. The Southern Altai mountain system, being a part of the East Kazakhstan administrative district, is known worldwide for its unique natural as well as cultural heritage found across all the geographic and geomorphic zones of the territory. Its unquestionable touristic-recreational attractiveness reflects the unique natural – both geomorphic and biodiversity – characteristics, including orographic, hydrological, climatic, mineral and soil cover features, and endemic plants and wildlife, respectively, completed by many prehistoric archaeological monuments. In spite of the major biotic and geosites potential the introduction of a vital and sustainable tourism to the area is impeded by the insufficient, mostly unpaved road network, insufficient local accommodation facilities as well as the special boarder-zone entry regulations. © 2018 Editura Universitatii din Oradea. All Rights Reserved

    Regulated Exocytosis of GABA-containing Synaptic-like Microvesicles in Pancreatic β-cells

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    We have explored whether γ-aminobutyric acid (GABA) is released by regulated exocytosis of GABA-containing synaptic-like microvesicles (SLMVs) in insulin-releasing rat pancreatic β-cells. To this end, β-cells were engineered to express GABAA-receptor Cl−-channels at high density using adenoviral infection. Electron microscopy indicated that the average diameter of the SLMVs is 90 nm, that every β-cell contains ∼3,500 such vesicles, and that insulin-containing large dense core vesicles exclude GABA. Quantal release of GABA, seen as rapidly activating and deactivating Cl−-currents, was observed during membrane depolarizations from −70 mV to voltages beyond −40 mV or when Ca2+ was dialysed into the cell interior. Depolarization-evoked GABA release was suppressed when Ca2+ entry was inhibited using Cd2+. Analysis of the kinetics of GABA release revealed that GABA-containing vesicles can be divided into a readily releasable pool and a reserve pool. Simultaneous measurements of GABA release and cell capacitance indicated that exocytosis of SLMVs contributes ∼1% of the capacitance signal. Mathematical analysis of the release events suggests that every SLMV contains 0.36 amol of GABA. We conclude that there are two parallel pathways of exocytosis in pancreatic β-cells and that release of GABA may accordingly be temporally and spatially separated from insulin secretion. This provides a basis for paracrine GABAergic signaling within the islet

    A MUSE map of the central Orion Nebula (M 42)

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    We present a new integral-field spectroscopic dataset of the central part of the Orion Nebula (M 42), observed with the MUSE instrument at the ESO VLT. We reduced the data with the public MUSE pipeline. The output products are two FITS cubes with a spatial size of ~5.9'x4.9' (corresponding to ~0.76 pc x 0.63 pc) and a contiguous wavelength coverage of 4595...9366 Angstrom, spatially sampled at 0.2". We provide two versions with a sampling of 1.25 Angstrom and 0.85 Angstrom in dispersion direction. Together with variance cubes these files have a size of 75 and 110 GiB on disk. They represent one of the largest integral field mosaics to date in terms of information content. We make them available for use in the community. To validate this dataset, we compare world coordinates, reconstructed magnitudes, velocities, and absolute and relative emission line fluxes to the literature and find excellent agreement. We derive a two-dimensional map of extinction and present de-reddened flux maps of several individual emission lines and of diagnostic line ratios. We estimate physical properties of the Orion Nebula, using the emission line ratios [N II] and [S III] (for the electron temperature TeT_e) and [S II] and [Cl III] (for the electron density NeN_e), and show two-dimensional images of the velocity measured from several bright emission lines.Comment: Resubmitted to A&A after incorporating referee comments; access to full dataset via http://muse-vlt.eu/science/data-release
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