261 research outputs found

    Development of an Information System to Enhance Students Reading Literacy

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    The research study at hand aims to answer the question, whether an innovative information system can be implemented that will help to enhance reading literacy of elementary pupils. Based on predefined reading tests this web-based system evaluates the reading literacy of pupils. It consists of two primary parts; the system that creates and evaluates such reading tests and the test platform itself. In order to assess the system a field test was conducted. Therefore it was tested in two school classes. In the course of this study reading tests were carried out and retrieved data and results were evaluated. Despite some minor usability problems, the system performed very well. The test system delivered good estimations of the reading capabilities of single pupils and classes. Of special interest is the system’s analysis of the created reading tests since the system is capable of evaluating reading test according to their difficult

    Erratum to: Spatial spin-up of fine scales in a regional climate model simulation driven by low-resolution boundary condition

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    The capture of the public servant in a criminal investigation is subject to special rules and different to those for the capture of individuals, since the imprisonment of an official can affect continuity, speed and efficiency of the civil service, an equally important constitutional value. Therefore, as a rule capturing the public servant must be preceded by a request for suspensión by the prosecution, and to proceed without suspension, the prosecutor in his providence should motivate the reasons and arguments why not affects the normal functioning of public administration. The lack of motivation for this essential aspect, affords a fact that becomes appropriate procedural habeas corpus as an effective mechanism guarantees of personal freedom. Similarly appropriate habeas corpus when catching public server ordered by a prosecutor without functional competence to advance research, by setting a path made by organic defect.La captura del servidor público investigado en un proceso penal está sujeta a reglas especiales y diversas a las previstas para la captura de los particulares, por cuanto la privación de la libertad de un funcionario puede afectar la continuidad, celeridad y eficacia de la función pública, como un valor constitucional igualmente relevante. Por tal motivo, como regla general,la captura del servidor público debe estar precedida de la solicitud de suspensión por parte de la Fiscalía General de la Nación y para que proceda sin suspensión previa, el fiscal debe consignar en su providencia las razones y argumentos por los cuales no se afecta el normal funcionamiento de la administración pública. La ausencia de motivación de este aspecto esencial constituye una vía de hecho procedimental que torna procedente la acción de habeas corpus, como mecanismo efectivo de garantía de la libertad personal. De igual manera, procede el habeas corpus cuando la captura del servidor público la ordena un fiscal sin competencia funcional para adelantar la investigación, por configuración de una vía de hecho por defecto orgánico

    Spatial spin-up of fine scales in a regional climate model simulation driven by low-resolution boundary conditions

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    In regional climate modelling, it is well known that domains should be neither too large to avoid a large departure from the driving data, nor too small to provide a sufficient distance from the lateral inflow boundary to allow the full development of the small-scale (SS) features permitted by the finer resolution. Although most practitioners of dynamical downscaling are well aware that the jump of resolution between the lateral boundary condition (LBC) driving data and the nested regional climate model affects the simulated climate, this issue has not been fully investigated. In principle, as the jump of resolution becomes larger, the region of interest in the limited-area domain should be located further away from the lateral inflow boundary to allow the full development of the SS features. A careless choice of domain might result in a suboptimal use of the full finer resolution potential to develop fine-scale features. To address this issue, regional climate model (RCM) simulations using various resolution driving data are compared following the perfect-prognostic Big-Brother protocol. Several experiments were carried out to evaluate the width of the spin-up region (i.e. the distance between the lateral inflow boundary and the domain of interest required for the full development of SS transient eddies) as a function of the RCM and LBC resolutions, as well as the resolution jump. The spin-up distance turns out to be a function of the LBC resolution only, independent of the RCM resolution. When varying the RCM resolution for a given resolution jump, it is found that the spin-up distance corresponds to a fixed number of RCM grid points that is a function of resolution jump only. These findings can serve a useful purpose to guide the choice of domain and RCM configuration for an optimal development of the small scales allowed by the increased resolution of the nested model

    Biochemical evidence for an ecto alkaline phosphodiesterase I in human airways

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    Because dinucleotides are signaling molecules that can interact with cell surface receptors and regulate the rate of mucociliary clearance in lungs, we studied their metabolism by using human airway epithelial cells. A membrane-bound enzyme was detected on the mucosal surface of polarized epithelia that metabolized dinucleotides with a broad substrate specificity (diadenosine polyphosphates and diuridine polyphosphates [Up(n)U], n = 2 to 6). The enzymatic reaction yielded nucleoside monophosphates (NMP) and Np(n-1) (N = A or U), and was inhibited by nucleoside 5'-triphosphates (α,βmet adenosine triphosphate [ATP] > ATP ≥ uridine triphosphate > guanidine triphosphate > cytidine triphosphate). The apparent Michaelis constant (K(m,app)) and apparent maximal velocity (V(max,app)) for [3H]Up4U were 22 ± 4 μM and 0.24 ± 0.05 nmoles · min-1 ·cm-2, respectively. Thymidine 5'-monophosphate p-nitrophenyl ester and adenosine diphosphate (ADP)-ribose, substrates of ecto alkaline phosphodiesterase I (PDE I) activities, were also hydrolyzed by the apical surface of airway epithelia. ADP-ribose competed with [3H]Up4U, with a K(i) of 23 ± 3 μM. The metabolism of ADP-ribose and Ap4A was not affected by inhibitors of cyclic nucleotide phosphodiesterases (3-isobutyl-1-methylxanthine, Ro 20-1724, and 1,3-dipropyl-8-p-sulfophenylxanthine), but similarly inhibited by fluoride and N-ethylmaleimide. These results suggest that a PDE I is responsible for the hydrolysis of extracellular dinucleotides in human airways. The wide substrate specificity of PDE I suggests that it may be involved in several signaling events on the luminal surface of airway epithelia, including purinoceptor activation and cell surface protein ribosylation

    Hot electron cooling by acoustic phonons in graphene

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    We have investigated the energy loss of hot electrons in metallic graphene by means of GHz noise thermometry at liquid helium temperature. We observe the electronic temperature T / V at low bias in agreement with the heat diffusion to the leads described by the Wiedemann-Franz law. We report on TVT\propto\sqrt{V} behavior at high bias, which corresponds to a T4 dependence of the cooling power. This is the signature of a 2D acoustic phonon cooling mechanism. From a heat equation analysis of the two regimes we extract accurate values of the electron-acoustic phonon coupling constant Σ\Sigma in monolayer graphene. Our measurements point to an important effect of lattice disorder in the reduction of Σ\Sigma, not yet considered by theory. Moreover, our study provides a strong and firm support to the rising field of graphene bolometric detectors.Comment: 5 figure

    Secreted and cell-associated adenylate kinase and nucleoside diphosphokinase contribute to extracellular nucleotide metabolism on human airway surfaces

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    5′-Nucleoside triphosphates (NTP) are present in the liquid covering airway surfaces and mediate important physiologic events through their interaction with P2-nucleotide receptors. Activation of airway P2Y2 receptors, for example, stimulates ciliary beat frequency, chloride/liquid secretion, and goblet cell degranulation. We, therefore, have studied the metabolic pathways that regulate the concentration of nucleotides on airway surfaces. Stimulation of submucosal gland secretion in the nose was previously found to decrease the concentration of 5′-adenosine triphosphate (ATP) in nasal lavage samples due to the presence of a secreted 5′-nucleoside triphosphatase (NTPase). In this study, gland secretions were further studied and found to also contain adenylate kinase (AK) and nucleoside diphosphokinase (NDPK) activities. Ecto-AK and ecto-NDPK activities were also detected in well-differentiated cultures of superficial nasal epithelia, which reflected a combination of cell-associated and released (into culture media) AK and NDPK activities. This study demonstrates that "ecto-kinases" on airway surfaces (1) emanate from different enzyme families, including both AK and NDPK; (2) are expressed at superficial epithelial surfaces and in submucosal glands; and (3) may be important regulators of nucleotide concentrations on airway surfaces

    Hair cells use active zones with different voltage dependence of Ca<sup>2+</sup> influx to decompose sounds into complementary neural codes.

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    For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs

    E-NTPDases in human airways: Regulation and relevance for chronic lung diseases

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    Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid ‘on-and-off’ signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP → ADP → AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage

    CAPTURE ALS: The comprehensive analysis platform to understand, remedy and eliminate ALS

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    The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants\u27 voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond

    Clinical pharmacology of exogenously administered alkaline phosphatase

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    Purpose: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). Methods: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg-124 h-1) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. Results: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. Conclusions: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis
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