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Alzheimer's disease-related mutations in the presenilin-1 gene (PS1) are leading to an elevated production of neurotoxic beta-amyloid 1-42 and may additionally enhance oxidative stress. Here, we provide in vivo evidence indicating that brains of transgenic mice expressing different human Alzheimer-linked PS1 mutations exhibit a reduced activity of two antioxidant enzymes. For this purpose, mice transgenic for human PS1 and for single and multiple PS1 mutations were generated. Mice with multiple PS1 mutations showed a significantly decreased activity of the antioxidant enzymes Cu/Zn superoxide dismutase and glutathione reductase already at an age of 3-4 months. As expected, this effect was less pronounced for the mice with a single PS1 mutation. By contrast, animals bearing normal human PS1 showed significantly elevated enzyme activities relative to non-transgenic littermate controls.
The identification of specific genetic (presenilin-1 [PS1] and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in which to study risk factors of sporadic, as well as genetic AD in vivo. The aim of our present study was to clarify whether lymphocytes bearing genetic or sporadic risk factors of AD share an increased susceptibility to cell death. Additionally we examined whether a cell typespecific vulnerability pattern was present and how normal aging, the main risk factor of sporadic AD, contributes to changes in susceptibility to cell death. Here, we report that lymphocytes affected by sporadic or genetic APP and PS1 AD risk factors share an increased vulnerability to cell death and exhibit a similar cell type-specific pattern, given that enhanced vulnerability was most strongly developed in the CD4+ T-cell subtype. In this paradigm, sporadic risk factors revealed the highest impact on cell type-specific sensitivity of CD4+ T cells to apoptosis. In contrast, normal aging results in an increased susceptibility to apoptosis of both, CD4+ and CD8+ T cells.
The microscopic phasespace approach URQMD is used to investigate the stopping power and particle production in heavy systems at SPS and RHIC energies. We find no gap in the baryon rapidity distribution even at RHIC. For CERN energies URQMD shows a pile up of baryons and a supression of multi-nucleon clusters at midrapidity.
The extension of the Periodic System into hitherto unexplored domains - anti- matter and hypermatter - is discussed. Starting from an analysis of hyperon and single hypernuclear properties we investigate the structure of multi-hyperon objects (MEMOs) using an extended relativistic meson field theory. These are contrasted with multi-strange quark states (strangelets). Their production mechanism is stud- ied for relativistic collisions of heavy ions from present day experiments at AGS and SPS to future opportunities at RHIC and LHC. It is pointed out that abso- lutely stable hypermatter is unlikely to be produced in heavy ion collisions. New attention should be focused on short lived metastable hyperclusters ( / 10 10s) and on intensity interferometry of multi-strange-baryon correlations.
In the framework of RQMD we investigate antiproton observables in massive heavy ion collisions at AGS energies and compare to preliminary results of the E878 collaboration. We focus here on the considerable influence of the real part of an antinucleon nucleus optical potential on the ¯p momentum spectra. Pacs-numbers: 14.20 Dh, 25.70.-z
In the framework of the relativistic quantum dynamics approach we investigate antiproton observables in Au-Au collisions at 10.7A GeV. The rapidity dependence of the in-plane directed transverse momentum p(y) of p's shows the opposite sigh of the nucleon flow, which has indeed recently been discovered at 10.7A GeV by the E877 group. The "antiflow" of p's is also predicted at 2A GeV and at 160 A GeV and appears at all energies also for pi's and K's. These predicted p anticorrelations are a direct proof of strong p annihilation in massive heavy ion reactions.
In the framework of the relativistic quantum molecular dynamics approach (RQMD) we investigate antideuteron (d) observables in Au+Au collisions at 10.7 AGeV. The impact parameter dependence of the formation ratios d/p2 and d/p2 is calculated. In central collisions, the antideuteron formation ratio is predicted to be two orders of magnitude lower than the deuteron formation ratio. The d yield in central Au+Au collisions is one order of magnitude lower than in Si+Al collisions. In semicentral collisions di erent configuration space distributions of p s and d s lead to a large squeeze out e ect for antideuterons, which is not predicted for the p s.
We present a RQMD calculation of antiproton yields and their momentum distribution in Ne + NaF collisions at 2 GeV/u. The antiprotons can be produced below threshold due to multi-step excitations for which meson-baryon interactions play a considerable role. In this system the annihilation probability for an initially produced antiproton is predicted to be about 65%.
Higher-order effects are calculated in the framework of the eigenchannel theory for elastic and inelastic electron-nucleus scattering in the energy region 100≤E≤250 MeV. A dispersion effect of about 12% is found for the elastic scattering on Ni58 at a momentum transfer q≈500 MeV/c. For inelastic scattering, the reorientation effect is discussed, in addition to the dispersion effect. The total higher-order effect changes the form factor for a hindered first-order transition by 50% at its minima. Furthermore, the dependence of the higher-order effects on the transition potentials of the virtual excitations, the model dependence, and the dependence on the energy E of the electron and the momentum transfer q are discussed. A closed formula for the S matrix is developed by calculating the eigenchannels in stationary perturbation theory.
Strange particle abundances in small volumes of hot hadronic gas are determined in the canonical ensemble with exact strangeness and baryon number conservation. Substantial density and baryon number dependence is found. A p¯d experiment is examined and applications to p¯-nucleus annihilations are considered.
Poster presentation: Background Maraviroc is a new drug used to treat HIV infection from the new class of drugs called CCR5 entry inhibitors. As the active principle of these drugs is to block the CCR5-receptor on the surface of the target cells, it has to be known if the virus in the patient is using only CCR5 as co-receptor or if there are populations that can also use CXCR4. Therefore, an assay to determine the tropism has to be performed before starting a therapy. Besides phenotypic assays like the TROFILE® assay by Monogram, used in the approval studies, there exist several genotyping systems like geno2pheno-coreceptor, Wetcat (providing five different genotypic tropism schemes) and WebPSSM. ...
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.