363 research outputs found

    The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence

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    The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case–control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA;N=81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N=22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P=0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P=0.033). The 168Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD

    Density fluctuations and single-particle dynamics in liquid lithium

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    The single-particle and collective dynamical properties of liquid lithium have been evaluated at several thermodynamic states near the triple point. This is performed within the framework of mode-coupling theory, using a self-consistent scheme which, starting from the known static structure of the liquid, allows the theoretical calculation of several dynamical properties. Special attention is devoted to several aspects of the single-particle dynamics, which are discussed as a function of the thermodynamic state. The results are compared with those of Molecular Dynamics simulations and other theoretical approaches.Comment: 31 pages (in preprint format), 14 figures. Submitted to Phys. Rev.

    Regional integration of long-term national dense GNSS network solutions

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    The EUREF Permanent Network Densification is a collaborative effort of 26 European GNSS analysis centers providing series of daily or weekly station position estimates of dense national and regional GNSS networks, in order to combine them into one homogenized set of station positions and velocities. During the combination, the station meta-data, including station names, DOMES numbers, and position offset definitions were carefully homogenized, position outliers were efficiently eliminated, and the results were cross-checked for any remaining inconsistencies. The results cover the period from March 1999 to January 2017 (GPS week 1000-1933) and include 31 networks with positions and velocities for 3192 stations, well covering Europe. The positions and velocities are expressed in ITRF2014 and ETRF2014 reference frames based on the Minimum Constraint approach using a selected set of ITRF2014 reference stations. The position alignment with the ITRF2014 is at the level of 1.5, 1.2, and 3.2 mm RMS for the East, North, Up components, respectively, while the velocity RMS values are 0.17, 0.14, and 0.38 mm/year for the East, North, and Up components, respectively. The high quality of the combined solution is also reflected by the 1.1, 1.1, and 3.5 mm weighted RMS values for the East, North, and Up components, respectively

    Regional integration of long-term national dense GNSS network solutions

    Get PDF
    The EUREF Permanent Network Densification is a collaborative effort of 26 European GNSS analysis centers providing series of daily or weekly station position estimates of dense national and regional GNSS networks, in order to combine them into one homogenized set of station positions and velocities. During the combination, the station meta-data, including station names, DOMES numbers, and position offset definitions were carefully homogenized, position outliers were efficiently eliminated, and the results were cross-checked for any remaining inconsistencies. The results cover the period from March 1999 to January 2017 (GPS week 1000-1933) and include 31 networks with positions and velocities for 3192 stations, well covering Europe. The positions and velocities are expressed in ITRF2014 and ETRF2014 reference frames based on the Minimum Constraint approach using a selected set of ITRF2014 reference stations. The position alignment with the ITRF2014 is at the level of 1.5, 1.2, and 3.2\ua0mm RMS for the East, North, Up components, respectively, while the velocity RMS values are 0.17, 0.14, and 0.38\ua0mm/year for the East, North, and Up components, respectively. The high quality of the combined solution is also reflected by the 1.1, 1.1, and 3.5\ua0mm weighted RMS values for the East, North, and Up components, respectively

    Morphology Analysis of Si Island Arrays on Si(001)

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    The formation of nanometer-scale islands is an important issue for bottom-up-based schemes in novel electronic, optoelectronic and magnetoelectronic devices technology. In this work, we present a detailed atomic force microscopy analysis of Si island arrays grown by molecular beam epitaxy. Recent reports have shown that self-assembled distributions of fourfold pyramid-like islands develop in 5-nm thick Si layers grown at substrate temperatures of 650 and 750°C on HF-prepared Si(001) substrates. Looking for wielding control and understanding the phenomena involved in this surface nanostructuring, we develop and apply a formalism that allows for processing large area AFM topographic images in a shot, obtaining surface orientation maps with specific information on facets population. The procedure reveals some noticeable features of these Si island arrays, e.g. a clear anisotropy of the in-plane local slope distributions. Total island volume analysis also indicates mass transport from the substrate surface to the 3D islands, a process presumably related to the presence of trenches around some of the pyramids. Results are discussed within the framework of similar island arrays in homoepitaxial and heteroepitaxial semiconductor systems

    Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia

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    Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals
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