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Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
The Coulomb Dissociation (CD) cross sections of the stable isotopes 92,94,100Mo and of the unstable isotope 93Mo were measured at the LAND/R3B setup at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Experimental data on these isotopes may help to explain the problem of the underproduction of 92,94Mo and 96,98Ru in the models of p-process nucleosynthesis. The CD cross sections obtained for the stable Mo isotopes are in good agreement with experiments performed with real photons, thus validating the method of Coulomb Dissociation. The result for the reaction 93Mo(γ,n) is especially important since the corresponding cross section has not been measured before. A preliminary integral Coulomb Dissociation cross section of the 94Mo(γ,n) reaction is presented. Further analysis will complete the experimental database for the (γ,n) production chain of the p-isotopes of molybdenum.
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Background: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, Major Depressive Disorder (MDD), patients only marginally differ from healthy individuals on the group-level. Whether Precision Psychiatry can solve this discrepancy and provide specific, reliable biomarkers remains unclear as current Machine Learning (ML) studies suffer from shortcomings pertaining to methods and data, which lead to substantial over-as well as underestimation of true model accuracy.
Methods: Addressing these issues, we quantify classification accuracy on a single-subject level in N=1,801 patients with MDD and healthy controls employing an extensive multivariate approach across a comprehensive range of neuroimaging modalities in a well-curated cohort, including structural and functional Magnetic Resonance Imaging, Diffusion Tensor Imaging as well as a polygenic risk score for depression.
Findings Training and testing a total of 2.4 million ML models, we find accuracies for diagnostic classification between 48.1% and 62.0%. Multimodal data integration of all neuroimaging modalities does not improve model performance. Similarly, training ML models on individuals stratified based on age, sex, or remission status does not lead to better classification. Even under simulated conditions of perfect reliability, performance does not substantially improve. Importantly, model error analysis identifies symptom severity as one potential target for MDD subgroup identification.
Interpretation: Although multivariate neuroimaging markers increase predictive power compared to univariate analyses, single-subject classification – even under conditions of extensive, best-practice Machine Learning optimization in a large, harmonized sample of patients diagnosed using state-of-the-art clinical assessments – does not reach clinically relevant performance. Based on this evidence, we sketch a course of action for Precision Psychiatry and future MDD biomarker research.
Dilepton spectra for p+p and p+d reactions at 4.9GeV are calculated. We consider electromagnetic bremsstrahlung also in inelastic reactions. N* and Delta* decay present the major contributions to the pho and omega meson yields.Pion annihilation yields only 1.5% of all pho's in p+d. The pho mass spectrum is strongly distorted due to phase space effects, populating dominantly dilepton masses below 770MeV.
An alternative theoretical description of axial electron channeling in the multi-GeV region has been developed. We solve a kinetic equation to evaluate an electron distribution function in axially oriented single crystals. Based on the single-string model, the required matrix elements for radiation and scattering by lattice vibrations are calculated employing solutions of the Dirac equation in cylindrical coordinates. Results obtained for 150-GeV electrons propagating along the <110> axis of germanium are in good agreement with experimental observations.
The Gottfried sum-rule violation reported by the New Muon Collaboration was interpreted as an indication for a flavor asymmetry of the sea quark in the nucleon. We investigate the alternative possibility that isospin symmetry between the proton and the neutron is breaking. We examine systematically the consequences of this possibility for several processes, namely, neutrino deep inelastic scattering, the charged pion Drell-Yan process, the proton Drell-Yan process, and semi-inclusive deep inelastic scattering, and conclude that a decision between the two alternative explanations is possible.
We investigate the possibility that high-energy photons are channeled, when passing through an oriented single crystal, due to Delbrück scattering. For this purpose the exact electron propagator for the single-string model is constructed. Starting from a separation of variables, we solve the Dirac equation for a cylindrical electrostatic potential. The propagator for such external fields is constructed from solutions of the radial Dirac equation. This propagator is applied to a calculation of the S matrix for Delbrück scattering. We specify the conditions under which photon channeling takes place. Unfortunately these conditions are only matched for a very small fraction of those photons being produced by channeled electrons.
The electron-positron pairs observed in heavy-ion collisions at Gesellschaft für Schwerionen-forschung Darmstadt mbH have been interpreted as the decay products of yet unknown particles with masses around 1.8 MeV. The negative results of resonant Bhabha scattering experiments, however, do not support such an interpretation. Therefore we focus on a more complex decay scenario, where the e+e- lines result from a two-collision process. We discuss the induced decay of a metastable 1++ state into e+e- pairs. For most realizations of a 1++ state such a decay in leading order can only take place in the Coulomb field of a target atom. This fact has the attractive consequence that for such a state the Bhabha bounds are no longer valid. However, the absolute value of the e+e- production cross section turns out to be unacceptably small.
We discuss the prospects for parity-nonconservation experiments with highly charged heavy ions. Energy levels and parity mixing for heavy ions with 2–5 electrons are calculated. We investigate two-photon transitions and the possibility of observing interference effects between weak-matrix elements and Stark matrix elements for periodic electric field configurations.