3,307 research outputs found

    Exploring attention-based explanations for some violations of Hick’s law for aimed movements

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    Choice reaction time generally increases linearly with the logarithm of the number of potential stimulus–response alternatives, a regularity known as Hick’s law. Two apparent violations of this generalization, which have been reported for aimed eye movements (Kveraga, Boucher, & Hughes, Experimental Brain Research, 146, 307–314, 2002), and arm movements (Wright, Marino, Belovsky, & Chubb, Experimental Brain Research, 179, 475–496, 2007), occurred when the indicator stimulus was an abrupt change at the location that was the target of the to-be-made movement. We report two experiments that examined and rejected the hypothesis that these abrupt-onset indicator stimuli triggered a shift in exogenous attention and that this led to unusually small uncertainty effects. Each experiment compared this indicator stimulus with a single alternative: Experiment 1 tested an indicator stimulus at all locations other than the target; Experiment 2 tested a central pointer to the target. Neither alternative led to an uncertainty effect for pointing responses that was of the size typically observed for other responses using the same stimuli

    Nanoparticle dynamics in hydrogel networks with controlled defects

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    The effect of nanoscale defects on nanoparticle dynamics in defective tetra-poly(ethylene glycol) (tetra-PEG) hydrogels is investigated using single particle tracking. In a swollen nearly homogeneous hydrogel, PEG-functionalized quantum dot (QD) probes with a similar hydrodynamic diameter (dh = 15.1 nm) to the mesh size (〈ξs〉 = 16.3 nm), are primarily immobile. As defects are introduced to the network by reaction-tuning, both the percentage of mobile QDs and the size of displacements increase as the number and size of the defects increase with hydrolysis time, although a large portion of the QDs remain immobile. To probe the effect of nanoparticle size on dynamics in defective networks, the transport of dh = 47.1 nm fluorescent polystyrene (PS) and dh = 9.6 nm PEG-functionalized QDs is investigated. The PS nanoparticles are immobile in all hydrogels, even in highly defective networks with an open structure. Conversely, the smaller QDs are more sensitive to perturbations in the network structure with an increased percentage of mobile particles and larger diffusion coefficients compared to the larger QDs and PS nanoparticles. The differences in nanoparticle mobility as a function of size suggests that particles of different sizes probe different length scales of the defects, indicating that metrics such as the confinement ratio alone cannot predict bulk dynamics in these systems. This study provides insight into designing hydrogels with controlled transport properties, with particular importance for degradable hydrogels for drug delivery applications

    GESTÃO ACADÊMICA E ADMINISTRATIVA UNIVERSITÁRIA EMPREENDEDORA

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    O estudo busca apresentar a importância de uma gestão acadêmica e administrativa universitária empreendedora, que propicie espaços acolhedores para o desenvolvimento e expansão de ideias dos gestores universitários. Os intraempreendedores neste estudo são os gestores universitários que conciliam seus objetivos próprios com os da instituição universitária em que trabalham. O apoio a ideias que podem dispor em seu ambiente universitário é um dos fatores determinantes para o sucesso da gestão acadêmica e administrativa universitária empreendedora. O artigo foi desenvolvido por intermédio de pesquisas bibliográficas em obras e sites da internet. Neste estudo observaram-se fatores e características que precisam estar presentes nas universidades para que haja uma gestão acadêmica e administrativa universitária empreendedora. Entre eles, o mais importante talvez não seja a remuneração que os gestores recebem, e sim a liberdade dada para solucionar problemas ou para dar andamento a um projeto

    Creating a Sport and Exercise Medicine Masters syllabus for doctors: a Delphi study

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    Objective Sport and Exercise Medicine (SEM) Masters curricula vary. This Delphi study is aimed to create a consensus curriculum for doctors undertaking SEM Masters courses. Methods A modified Delphi survey was used. An expert panel was established of individuals deemed to have adequate knowledge of the field. The research group developed the initial draft of the curriculum by collating and reviewing previously published UK-based postgraduate SEM-related curricula. There were two phases. In phase 1 the expert group either accepted, rejected or modified each learning objective (LO). During phase 2 the expert group were asked to accept or reject each LO that did not get accepted outright previously. The research group analysed the levels of agreements and the comments given by the expert panel after each phase. Results The expert panel consisted of 45 individuals, with 35 completing phase 2 (78% retention rate). Of the 136 LOs initially collated: 71 (52%) were accepted outright, 60 (44%) were altered in some way and reincluded in phase 2, and 5 (4%) were removed after phase 1. The research group added 2 (1%) new LOs on reflection over comments made by the expert panel. The final curriculum contained 133 LOs, divided into 11 subthemes. Conclusions The findings will better inform educators when developing SEM Masters curricula and inform students what they should look for when considering an SEM Masters. This consensus curriculum is an important step in standardising postgraduate SEM education

    Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

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    With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

    A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

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    During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

    Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice

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    Background Cancer-associated bone disease is a serious complication in bone sarcomas and metastatic carcinomas of breast and prostate origin. Monoacylglycerol lipase (MAGL) is an enzyme of the endocannabinoid system, and is responsible for the degradation of the most abundant endocannabinoid in bone, 2-arachidonoyl glycerol (2AG). Methods The effects of the verified MAGL inhibitor on bone remodelling were assessed in healthy mice and in mouse models of bone disease caused by prostate and breast cancers and osteosarcoma. Findings JZL184 reduced osteolytic bone metastasis in mouse models of breast and prostate cancers, and inhibited skeletal tumour growth, metastasis and the formation of ectopic bone in models of osteosarcoma. Additionally, JZL184 suppressed cachexia and prolonged survival in mice injected with metastatic osteosarcoma and osteotropic cancer cells. Functional and histological analysis revealed that the osteoprotective action of JZL184 in cancer models is predominately due to inhibition of tumour growth and metastasis. In the absence of cancer, however, exposure to JZL184 exerts a paradoxical reduction of bone volume via an effect that is mediated by both Cnr1 and Cnr2 cannabinoid receptors. Interpretation MAGL inhibitors such as JZL184, or its novel analogues, may be of value in the treatment of bone disease caused by primary bone cancer and bone metastasis, however, activation of the skeletal endocannabinoid system may limit their usefulness as osteoprotective agents

    Complete atrioventricular canal

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    Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification). CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators) plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life

    Efficient and Specific Analysis of Red Blood Cell Glycerophospholipid Fatty Acid Composition

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    Red blood cell (RBC) n-3 fatty acid status is related to various health outcomes. Accepted biological markers for the fatty acid status determination are RBC phospholipids, phosphatidylcholine, and phosphatidyletholamine. The analysis of these lipid fractions is demanding and time consuming and total phospholipid n-3 fatty acid levels might be affected by changes of sphingomyelin contents in the RBC membrane during n-3 supplementation. We developed a method for the specific analysis of RBC glycerophospholipids. The application of the new method in a DHA supplementation trial and the comparison to established markers will determine the relevance of RBC GPL as a valid fatty acid status marker in humans. Methyl esters of glycerophospholipid fatty acids are selectively generated by a two step procedure involving methanolic protein precipitation and base-catalysed methyl ester synthesis. RBC GPL solubilisation is facilitated by ultrasound treatment. Fatty acid status in RBC glycerophospholipids and other established markers were evaluated in thirteen subjects participating in a 30 days supplementation trial (510 mg DHA/d). The intra-assay CV for GPL fatty acids ranged from 1.0 to 10.5% and the inter-assay CV from 1.3 to 10.9%. Docosahexaenoic acid supplementation significantly increased the docosahexaenoic acid contents in all analysed lipid fractions. High correlations were observed for most of the mono- and polyunsaturated fatty acids, and for the omega-3 index (r = 0.924) between RBC phospholipids and glycerophospholipids. The analysis of RBC glycerophospholipid fatty acids yields faster, easier and less costly results equivalent to the conventional analysis of RBC total phospholipids
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