239 research outputs found

    Alterations in Task-Related Brain Activation in Children, Adolescents and Young Adults at Familial High-Risk for Schizophrenia or Bipolar Disorder - A Systematic Review.

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    Children, adolescents, and young adults with at least one first-degree relative [familial high-risk (FHR)] with either schizophrenia (SZ) or bipolar disorder (BD) have a one-in-two risk of developing a psychiatric disorder. Here, we review functional magnetic resonance imaging (fMRI) studies which examined task-related brain activity in young individuals with FHR-SZ and FHR-BD. A systematic search identified all published task-related fMRI studies in children, adolescents, and young adults below an age of 27 years with a first-degree relative with SZ or BD, but without manifest psychotic or affective spectrum disorder themselves. The search identified 19 cross-sectional fMRI studies covering four main cognitive domains: 1) working memory (n = 3), 2) cognitive control (n = 4), 3) reward processing (n = 3), and 4) emotion processing (n = 9). Thirteen studies included FHR-BD, five studies included FHR-SZ, and one study included a pooled FHR group. In general, task performance did not differ between the respective FHR groups and healthy controls, but 18 out of the 19 fMRI studies revealed regional alterations in task-related activation. Brain regions showing group differences in peak activation were regions associated with the respective task domain and showed little overlap between FHR-SZ and FHR-BD. The low number of studies, together with the low number of subjects, and the substantial heterogeneity of employed methodological approaches within the domain of working memory, cognitive control, and reward processing impedes finite conclusions. Emotion processing was the most investigated task domain in FHR-BD. Four studies reported differences in activation of the amygdala, and two studies reported differences in activation of inferior frontal/middle gyrus. Together, these studies provide evidence for altered brain processing of emotions in children, adolescents, and young adults at FHR-BD. More studies of higher homogeneity, larger sample sizes and with a longitudinal study design are warranted to prove a shared or specific FHR-related endophenotypic brain activation in young first-degree relatives of individuals with SZ or BD, as well as to pinpoint specific alterations in brain activation during cognitive-, emotional-, and reward-related tasks

    Matching gauge theory and string theory in a decoupling limit of AdS/CFT

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    We identify a regime of the AdS/CFT correspondence in which we can quantitatively match N=4 super Yang-Mills (SYM) for small 't Hooft coupling with weakly coupled type IIB string theory on AdS_5 x S^5. We approach this regime by taking the same decoupling limit on both sides of the correspondence. On the gauge theory side only the states in the SU(2) sector survive, and in the planar limit the Hamiltonian is given by the XXX_{1/2} Heisenberg spin chain. On the string theory side we show that the decoupling limit corresponds to a non-relativistic limit. In this limit some of the bosonic modes and all of the fermionic modes of the string become infinitely heavy and decouple. We first take the decoupling limit of the string sigma-model classically. This enables us to identify a semi-classical regime with semi-classical string states even though we are in a regime corresponding to small 't Hooft coupling. We furthermore analyze the quantum corrections that enter in taking the limit. From this we infer that gauge theory and string theory match, both in terms of the action and the spectrum, for the leading part and the first correction away from the semi-classical regime. Finally we consider the implications for the hitherto unexplained matching of the one-loop contribution to the energy of certain gauge theory and string theory states, and we explain how our results give a firm basis for the matching of the Hagedorn temperature in hep-th/0608115.Comment: 29 pages, 1 figure. v2: Version published in JHEP, section 4 improve

    Strings on conifolds from strong coupling dynamics, part I

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    A method to solve various aspects of the strong coupling expansion of the superconformal field theory duals of AdS_5 x X geometries from first principles is proposed. The main idea is that at strong coupling the configurations that dominate the low energy dynamics of the field theory compactified on a three sphere are given by certain non-trivial semi-classical configurations in the moduli space of vacua. We show that this approach is self-consistent and permits one to express most of the dynamics in terms of an effective N=4 SYM dynamics. This has the advantage that some degrees of freedom that move the configurations away from moduli space can be treated perturbatively, unifying the essential low energy dynamics of all of these theories. We show that with this formalism one can compute the energies of strings in the BMN limit in the Klebanov-Witten theory from field theory considerations, matching the functional form of results found using AdS geometry. This paper also presents various other technical results for the semiclassical treatment of superconformal field theories.Comment: 52 pages, JHEP3 styl

    Technical summary

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    Human interference with the climate system is occurring. Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC's Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change and how risks can be reduced through mitigation and adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of mitigation and adaptation

    Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

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    The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at s=900\sqrt{s} = 900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (η<0.8)(|\eta|<0.8) over the transverse momentum range 0.15<pT<100.15<p_{\rm T}<10 GeV/cc. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for η<0.8|\eta|<0.8 is <pT>INEL=0.483±0.001\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001 (stat.) ±0.007\pm0.007 (syst.) GeV/cc and \left_{\rm NSD}=0.489\pm0.001 (stat.) ±0.007\pm0.007 (syst.) GeV/cc, respectively. The data exhibit a slightly larger <pT>\left<p_{\rm T}\right> than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

    A MODEST review

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    We present an account of the state of the art in the fields explored by the research community invested in 'Modeling and Observing DEnse STellar systems'. For this purpose, we take as a basis the activities of the MODEST-17 conference, which was held at Charles University, Prague, in September 2017. Reviewed topics include recent advances in fundamental stellar dynamics, numerical methods for the solution of the gravitational N-body problem, formation and evolution of young and old star clusters and galactic nuclei, their elusive stellar populations, planetary systems, and exotic compact objects, with timely attention to black holes of different classes of mass and their role as sources of gravitational waves. Such a breadth of topics reflects the growing role played by collisional stellar dynamics in numerous areas of modern astrophysics. Indeed, in the next decade, many revolutionary instruments will enable the derivation of positions and velocities of individual stars in the Milky Way and its satellites and will detect signals from a range of astrophysical sources in different portions of the electromagnetic and gravitational spectrum, with an unprecedented sensitivity. On the one hand, this wealth of data will allow us to address a number of long-standing open questions in star cluster studies; on the other hand, many unexpected properties of these systems will come to light, stimulating further progress of our understanding of their formation and evolution.Comment: 42 pages; accepted for publication in 'Computational Astrophysics and Cosmology'. We are much grateful to the organisers of the MODEST-17 conference (Charles University, Prague, September 2017). We acknowledge the input provided by all MODEST-17 participants, and, more generally, by the members of the MODEST communit

    Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

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    Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation
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