1,387 research outputs found

    Delay and probabilistic discounting of alcoholic beverages

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    Discounting tasks were used to determine the degree to which college undergraduates discounted delayed and probabilistic alcoholic beverages. Tasks were framed in terms of gains (i.e.,obtaining a hypothetical amount of alcohol) and losses (i.e., losing a hypothetical amount of alcohol). In all gain and loss conditions, discounting was evident and was generally well described by a hyperboloid function. Gains were discounted more steeply then losses. There were no correlations between the median delay gain discounting rates and the median delay loss discounting rates. Likewise, there were no correlations between the median probabilistic gain discounting rates and the median probabilistic loss discounting rates. This pattern of results suggests that each condition is independent from one another, operating under a separate set of mental processes. Future studies with a larger sample size are necessary to validate these findings

    Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome

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    Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O’Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033–2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS

    Requirements for sulfate transport and the diastrophic dysplasia sulfate transporter in fibronectin matrix assembly

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    Diastrophic dysplasia sulfate transporter (DTDST) is a sulfate/chloride antiporter whose function is impaired in several human chondrodysplasias. We show that DTDST is upregulated by dexamethasone stimulation of HT1080 fibrosarcoma cells and is required for fibronectin (FN) extracellular matrix deposition by these cells. DTDST imports sulfate for the modification of glycosaminoglycans. We find that N-sulfation of these chains is important for FN matrix assembly and that sulfation of cell surface proteoglycans is reduced in the absence of DTDST. Of the candidate HT1080 cell surface proteoglycans, only loss of syndecan-2 compromises FN assembly, as shown by syndecan-2 small interfering RNA knockdown. DTDST is both necessary and sufficient to induce FN matrix assembly in HT1080 cells. Knockdown of DTDST ablates FN matrix, whereas its overexpression increases assembly without dexamethasone stimulation. These results identify a previously unrecognized regulatory pathway for matrix assembly via modulation of a sulfate transporter and proteoglycan sulfation. These data raise the possibility that FN assembly defects contribute to chondrodysplasias

    Pharmaceutical vehicles for vaginal and rectal administration of anti-hiv microbicide nanosystems

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    Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most efforts have been placed in finding and testing suitable active drug candidates to be used in microbicide development, the last decade also saw considerable advances in the design of adequate carrier systems and formulations that could lead to products presenting enhanced performance in protecting from infection. One strategy demonstrating great potential encompasses the use of nanosystems, either with intrinsic antiviral activity or acting as carriers for promising microbicide drug candidates. Polymeric nanoparticles, in particular, have been shown to be able to enhance mucosal distribution and retention of promising antiretroviral compounds. One important aspect in the development of nanotechnology-based microbicides relates to the design of pharmaceutical vehicles that allow not only convenient vaginal and/or rectal administration, but also preserve or even enhance the performance of nanosystems. In this manuscript, we revise relevant work concerning the selection of vaginal/rectal dosage forms and vehicle formulation development for the administration of microbicide nanosystems. We also pinpoint major gaps in the field and provide pertinent hints for future work.This work was supported by Programa Gilead GÉNESE, Gilead Portugal (refs. PGG/046/2015 and PGG/002/2016). This article is a result of the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and also Partnership Agreement PT2020 UID/QUI/50006/2013-POCI/01/0145/FEDER/007265. J.G. gratefully acknowledges FCT for financial support (SFRH/BD/140271/2018 scholarship)

    Role of longitudinal fluctuations in L10 FePt

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    L10 FePt is a technologically important material for a range of novel data storage applications. In the ordered FePt structure the normally nonmagnetic Pt ion acquires a magnetic moment, which depends on the local field originating from the neighboring Fe atoms. In this work a model of FePt is constructed in which the induced Pt moment is simulated by using combined longitudinal and rotational spin dynamics. The model is parameterized to include a linear variation of the moment with the exchange field, so that at the Pt site the magnetic moment depends on the Fe ordering. The Curie temperature of FePt is calculated and agrees well with similar models that incorporate the Pt dynamics through an effective Fe-only Hamiltonian. By computing the dynamic correlation function the anisotropy field and the Gilbert damping are extracted over a range of temperatures. The anisotropy exhibits a power-law dependence on the magnetization with exponent n≈2.1. This agrees well with what was observed experimentally, and it is obtained without including a two-ion anisotropy term as in other approaches. Our work shows that incorporating longitudinal fluctuations into spin dynamics calculations is crucial for understanding the properties of materials with induced moments

    Data Collection for Traffic and Drivers’ Behaviour Studies: A Large-scale Survey

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    AbstractStudies of driving behaviour are of great help for different tasks in transportation engineering. These include data collection both for statistical analysis and for identification of driving models and estimation of modelling parameters (calibration). The data and models may be applied to different areas: i) road safety analysis; ii) microscopic models for traffic simulation, forecast and control; iii) control logics aimed at ADAS (Advanced Driving Assistance Systems). In this paper we present a large survey based on the naturalistic (on-the-road) observation of driving behaviour with a view to obtaining microscopic data for single vehicles on long road segments and for long time periods. Data are collected by means of an instrumented vehicle (IV), equipped with GPS, radar, cameras and other sensors. The behaviour of more than 100 drivers was observed by using the IV in active mode, that is by observing the kinematics imposed on the vehicle by the driver, as well as the kinematics with respect to neighbouring vehicles. Sensors were also mounted backwards on the IV, allowing the behaviour of the driver behind to be observed in passive mode. As the vehicle behind changes, the next is observed and within a short period of time the behaviour of several drivers can be examined, without the observed driver being aware. The paper presents the experiment by describing the road context, aims and experimental procedure. Statistics and initial insights are also presented based on the large amount of data collected (more than 8000km of observed trajectories and 120hours of driving in active mode). As an example of how to use the data directly, apart from calibration of driving behaviour models, indexes based on aggregate measures of safety are computed, presented and discussed

    Development and Application of a Loop-Mediated Isothermal Amplification (LAMP) Approach for the Rapid Detection of Dirofilaria repens from Biological Samples

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    Dirofilariasis by Dirofilaria repens is an important mosquito vector borne parasitosis, and the dog represents the natural host and reservoir of the parasite. This filarial nematode can also induce disease in humans, and in the last decades an increasing number of cases have been being reported. The present study describes the first loop mediated isothermal amplification (LAMP) assay to detect D. repens DNA in blood and mosquitoes. Two versions of the technique have been developed and described: in the first, the amplification is followed point by point through a real time PCR instrument (ReT-LAMP); in the second, the amplification is visualized by checking UV fluorescence of the reaction mixture after addition of propidium iodide (PI-LAMP). The two variants use the same set of 4 primers targeting the D. repens cytochrome oxidase subunit I (COI) gene. To assess the specificity of the method, reactions were carried out by using DNA from the major zoonotic parasites of the family of Onchocercidae, and no amplification was observed. The lower limit of detection of the ReT-LAMP assay was 0.15 fg/μl (corresponding to about 50 copy of COI gene per μl). Results suggest that the described assay is specific, and its sensitivity is higher than the conventional PCR based on the same gene. It is also provide a rapid and cost-effective molecular detection of D. repens, mainly when PI-LAMP is applied, and it should be performed in areas where this emerging parasitosis is endemic
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