364 research outputs found

    Using coupled micropillar compression and micro-Laue diffraction to investigate deformation mechanisms in a complex metallic alloy Al13Co4

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    In this investigation, we have used in-situ micro-Laue diffraction combined with micropillar compression of focused ion beam milled Al13Co4 complex metallic alloy to study the evolution of deformation in Al13Co4. Streaking of the Laue spots showed that the onset of plastic flow occured at stresses as low as 0.8 GPa, although macroscopic yield only becomes apparent at 2 GPa. The measured misorientations, obtained from peak splitting, enabled the geometrically necessary dislocation density to be estimated as 1.1 x 1013 m-2

    The study of personality preschool children in modern foreign research

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    The article deals with the problem of studying and describing the personality of the child in the preschool age. Provides the review of modern foreign studies on this issue. Grounded the importance of age characteristics for describing the structure of the child's personality.В статье рассматривается проблема изучения и описания личности ребенка в дошкольном возрасте. Представлен обзор современных зарубежных исследований, посвященных данному вопросу. Обосновывается важность возрастных характеристик для описания структуры личности ребенка

    A Bitter Pill: The Primordial Lithium Problem Worsens

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    The lithium problem arises from the significant discrepancy between the primordial 7Li abundance as predicted by BBN theory and the WMAP baryon density, and the pre-Galactic lithium abundance inferred from observations of metal-poor (Population II) stars. This problem has loomed for the past decade, with a persistent discrepancy of a factor of 2--3 in 7Li/H. Recent developments have sharpened all aspects of the Li problem. Namely: (1) BBN theory predictions have sharpened due to new nuclear data, particularly the uncertainty on 3He(alpha,gamma)7Be, has reduced to 7.4%, and with a central value shift of ~ +0.04 keV barn. (2) The WMAP 5-year data now yields a cosmic baryon density with an uncertainty reduced to 2.7%. (3) Observations of metal-poor stars have tested for systematic effects, and have reaped new lithium isotopic data. With these, we now find that the BBN+WMAP predicts 7Li/H = (5.24+0.71-0.67) 10^{-10}. The Li problem remains and indeed is exacerbated; the discrepancy is now a factor 2.4--4.3 or 4.2sigma (from globular cluster stars) to 5.3sigma (from halo field stars). Possible resolutions to the lithium problem are briefly reviewed, and key nuclear, particle, and astronomical measurements highlighted.Comment: 21 pages, 4 figures. Comments welcom

    Enhanced tonic GABAA inhibition in typical absence epilepsy

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    The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

    NR4A Gene Expression Is Dynamically Regulated in the Ventral Tegmental Area Dopamine Neurons and Is Related to Expression of Dopamine Neurotransmission Genes

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    The NR4A transcription factors NR4A1, NR4A2, and NR4A3 (also known as Nur77, Nurr1, and Nor1, respectively) share similar DNA-binding properties and have been implicated in regulation of dopamine neurotransmission genes. Our current hypothesis is that NR4A gene expression is regulated by dopamine neuron activity and that induction of NR4A genes will increase expression of dopamine neurotransmission genes. Eticlopride and γ-butyrolactone (GBL) were used in wild-type (+/+) and Nurr1-null heterozygous (+/−) mice to determine the mechanism(s) regulating Nur77 and Nurr1 expression. Laser capture microdissection and real-time PCR was used to measure Nurr1 and Nur77 mRNA levels in the ventral tegmental area (VTA). Nur77 expression was significantly elevated 1 h after both GBL (twofold) and eticlopride (fourfold). In contrast, GBL significantly decreased Nurr1 expression in both genotypes, while eticlopride significantly increased Nurr1 expression only in the +/+ mice. In a separate group of mice, haloperidol injection significantly elevated Nur77 and Nor1, but not Nurr1 mRNA in the VTA within 1 h and significantly increased tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA expression by 4 h. These data demonstrate that the NR4A genes are dynamically regulated in dopamine neurons with maintenance of Nurr1 expression requiring dopamine neuron activity while both attenuation of dopamine autoreceptors activation and dopamine neuronal activity combining to induce Nur77 expression. Additionally, these data suggest that induction of NR4A genes could regulate TH and DAT expression and ultimately regulate dopamine neurotransmission

    26S Proteasome Activity Is Down-Regulated in Lung Cancer Stem-Like Cells Propagated In Vitro

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    Cancer stem cells (CSCs) are a small subset of cancer cells capable of self-renewal and tumor maintenance. Eradicating cancer stem cells, the root of tumor origin and recurrence, has emerged as one promising approach to improve lung cancer survival. Cancer stem cells are reported to reside in the side population (SP) of cultured lung cancer cells. We report here the coexistence of a distinct population of non-SP (NSP) cells that have equivalent self-renewal capacity compared to SP cells in a lung tumor sphere assay. Compared with the corresponding cells in monolayer cultures, lung tumor spheres, formed from human non-small cell lung carcinoma cell lines A549 or H1299, showed marked morphologic differences and increased expression of the stem cell markers CD133 and OCT3/4. Lung tumor spheres also exhibited increased tumorigenic potential as only 10,000 lung tumor sphere cells were required to produce xenografts tumors in nude mice, whereas the same number of monolayer cells failed to induce tumors. We also demonstrate that lung tumor spheres showed decreased 26S proteasome activity compared to monolayer. By using the ZsGreen–cODC (C-terminal sequence that directs degradation of Ornithine Decarboxylase) reporter assay in NSCLC cell lines, only less than 1% monolayer cultures were ZsGreen positive indicating low 26S proteasome, whereas lung tumor sphere showed increased numbers of ZsGreen-positive cells, suggesting the enrichment of CSCs in sphere cultures

    Evaluation of strain and stress states in the single point incremental forming process

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    Single point incremental forming (SPIF) is a promising manufacturing process suitable for small batch production. Furthermore, the material formability is enhanced in comparison with the conventional sheet metal forming processes, resulting from the small plastic zone and the incremental nature. Nevertheless, the further development of the SPIF process requires the full understanding of the material deformation mechanism, which is of great importance for the effective process optimization. In this study, a comprehensive finite element model has been developed to analyse the state of strain and stress in the vicinity of the contact area, where the plastic deformation increases by means of the forming tool action. The numerical model is firstly validated with experimental results from a simple truncated cone of AA7075-O aluminium alloy, namely, the forming force evolution, the final thickness and the plastic strain distributions. In order to evaluate accurately the through-thickness gradients, the blank is modelled with solid finite elements. The small contact area between the forming tool and the sheet produces a negative mean stress under the tool, postponing the ductile fracture occurrence. On the other hand, the residual stresses in both circumferential and meridional directions are positive in the inner skin of the cone and negative in the outer skin. They arise predominantly along the circumferential direction due to the geometrical restrictions in this direction.The authors would like to gratefully acknowledge the financial support from the Portuguese Foundation for Science and Technology (FCT) under project PTDC/EMS-TEC/1805/2012. The first author is also grateful to the FCT for the postdoctoral grant SFRH/BPD/101334/2014.info:eu-repo/semantics/publishedVersio

    Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

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    Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio <1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studie
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