278 research outputs found

    A selective strategy for targeting primary hyperoxaluria diseases

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    Funding Information: Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). This work was partially supported by the Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). Funding Information: This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). This work was partially supported by the Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). Funding Information: Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. Publisher Copyright: © 2022 The Author(s)Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8–24.5 %) and encapsulation efficiencies (31.9–40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 μM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 μM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.publishersversionpublishe

    Pseudo-transient Continuation, Solution Update Methods, and CFL Strategies for DG Discretizations of the RANS-SA Equations

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106459/1/AIAA2013-2686.pd

    Large CSC chamber for the PHENIX muon detector with ultra thin cathode foils

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    The muon tracking system for the PHENIX detector at RHIC uses cathode strip chambers (CSC) for the tracking detectors. These detectors must provide 100 μm resolution per measurement plane to give satisfactory mass resolution of the vector mesons. The intermediate station (station 2) must have a very small radiation length, and large acceptance. We have prototyped a full scale CSC chamber to test the use of 25 micron metalized mylar foils for the cathode strips at station 2. The full scale prototype detector is a trapezoid 2.3 meters high and 2.3 meters wide. The foil and wire planes are mounted on thin 3,2 mm thick by 7.5 cm wide laminated frames and the tension of the planes is maintained by the two large 7.5 cm widex3.0 cm thick aluminum support frames. The total radiation length of the active region is 8.5x104

    Search for the lepton-family-number nonconserving decay \mu -> e + \gamma

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    The MEGA experiment, which searched for the muon- and electron-number violating decay \mu -> e + \gamma, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio of \mu -> e + \gamma) < 1.2 x 10^{-11} was obtained

    Freshwater ecoregions of the world: A new map of biogeographic units for freshwater biodiversity conservation

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    We present a new map depicting the first global biogeographic regionalization of Earth's freshwater systems. This map of freshwater ecoregions is based on the distributions and compositions of freshwater fish species and incorporates major ecological and evolutionary patterns. Covering virtually all freshwater habitats on Earth, this ecoregion map, together with associated species data, is a useful tool for underpinning global and regional conservation planning efforts (particularly to identify outstanding and imperiled freshwater systems); for serving as a logical framework for large-scale conservation strategies; and for providing a global-scale knowledge base for increasing freshwater biogeographic literacy. Preliminary data for fish species compiled by ecoregion reveal some previously unrecognized areas of high biodiversity, highlighting the benefit of looking at the world's freshwaters through a new framework.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Naturales y Muse

    Freshwater ecoregions of the world: A new map of biogeographic units for freshwater biodiversity conservation

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    We present a new map depicting the first global biogeographic regionalization of Earth's freshwater systems. This map of freshwater ecoregions is based on the distributions and compositions of freshwater fish species and incorporates major ecological and evolutionary patterns. Covering virtually all freshwater habitats on Earth, this ecoregion map, together with associated species data, is a useful tool for underpinning global and regional conservation planning efforts (particularly to identify outstanding and imperiled freshwater systems); for serving as a logical framework for large-scale conservation strategies; and for providing a global-scale knowledge base for increasing freshwater biogeographic literacy. Preliminary data for fish species compiled by ecoregion reveal some previously unrecognized areas of high biodiversity, highlighting the benefit of looking at the world's freshwaters through a new framework.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Naturales y Muse

    Convergence of the steepest descent method for minimizing quasiconvex functions

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    To minimize a continuously differentiable quasiconvex function f : ℝ n →ℝ, Armijo's steepest descent method generates a sequence x k +1 = x k − t k ∇ f ( x k ), where t k >0. We establish strong convergence properties of this classic method: either , s.t. ; or arg min f = ∅, ∥ x k ∥ ↓ ∞ and f(x k )↓ inf f . We also discuss extensions to other line searches.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45245/1/10957_2005_Article_BF02192649.pd

    The impact of positive psychological interventions on well-being in healthy elderly people

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    This systematic review aims to evaluate the impact of Positive Psychological Interventions (PPIs) on well-being in healthy older adults. Systematic review of PPIs obtained from three electronic databases (PsycINFO, Scopus, and Web of Science) was undertaken. Inclusion criteria were: that they were positive psychology intervention, included measurement of well-being, participants were aged over 60 years, and the studies were in English. The Cochrane Collaboration Guidelines dimensions of quality control, randomization, comparability, follow-up rate, dropout, blinding assessors are used to rate the quality of studies by two reviewers independently. The RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) for evaluation of PPIs effectiveness was also applied. The final review included eight articles, each describing a positive psychological intervention study. The reminiscence interventions were the most prevalent type of PPIs to promote and maintain well-being in later life. Only two studies were rated as high quality, four were of moderate-quality and two were of low-quality. Overall results indicated that efficacy criteria (89%), reach criteria (85%), adoption criteria (73%), implementation criteria (67%), and maintenance criteria (4%) across a variety of RE-AIM dimensions. Directions for future positive psychological research related to RE-AIM, and implications for decision-making, are described

    Seismic site characterization of the Kastelli (Kissamos) Basin in northwest Crete (Greece): Assessments using ambient noise recordings

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    Crete is actively seismic and site response studies are needed for estimating local site conditions subjected to seismic activity. In order to collect basic data, we performed ambient noise recordings to estimate the site response of the surface and near subsurface structure of the small-scale Kastelli Basin in northwest Crete. The spatial horizontal to vertical spectral ratios (HVSR) resonance pattern of the investigated sites in the centre of the Basin consists of either one or two peaks divided into low to high frequency range in different sites as follows: (a) in some sites only one amplified peak at low frequencies (0.6–1.2 Hz), (b) in other sites only one amplified peak at medium frequencies (2.9–8.5 Hz) and (c) in yet other sites two amplified peaks in the low to high frequency range (0.6–15.5 Hz). The investigated sites are amplified in the frequency range 0.6–15.5 Hz, while the amplitude reaches to a factor of 4 in the spectral ratios. The one HVSR amplified peak at low frequencies is related to locally soft or thick Quaternary deposits. Microtremors were measured in the coastal northwest part of the Basin in a well—lithified Cretaceous limestone site characterized by fractures and faults striking predominantly in a sector NNE to NNW. Sites of one amplified peak at medium frequencies are extended from coastal northwest to southwest delineating a structure striking to NNW. The two amplified peaks are attributed to shallow subsurface heterogeneities/irregularities, locally induced by fault zones and to the overlying Quaternary deposits. Spatial HVSR variations in the frequency and HVSR shape delineate four structures striking NNE, NNW and in a sector NW to WNW, crosscutting the dense populated Basin suggesting that microtremors could be a valuable tool for providing a first approximation of fault zone delineation at least for the Kastelli-Kissamos Basin. The Basin is classified into the X soil category of the Greek Seismic Code 2000.This work was implemented through the project entitled “Interdisciplinary Multi-Scale Research of Earth-quake Physics and Seismotectonics at the Front of the Hellenic Arc (IMPACT-ARC)” in the framework of action “ARCHIMEDES III—Support of Research Teams at TEI of Crete” (MIS380353) of the Operational Program “Education and Lifelong Learning” and is co-financed by the European Union (European Social Fund) and Greek national fund
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