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We study the thermodynamic properties of infinite nuclear matter with the Ultrarelativistic Quantum Molecular Dynamics (URQMD), a semiclassical transport model, running in a box with periodic boundary conditions. It appears that the energy density rises faster than T4 at high temperatures of T approx. 200 - 300 MeV. This indicates an increase in the number of degrees of freedom. Moreover, We have calculated direct photon production in Pb+Pb collisions at 160 GeV/u within this model. The direct photon slope from the microscopic calculation equals that from a hydrodynamical calculation without a phase transition in the equation of state of the photon source.
Nonequilibrium models (three-fluid hydrodynamics, UrQMD, and quark molecular dynamics) are used to discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions from the SPS via RHIC to LHC. It is demonstrated that these models - although they do treat the most interesting early phase of the collisions quite differently (thermalizing QGP vs. coherent color fields with virtual particles) -- all yield a reasonable agreement with a large variety of the available heavy ion data. Hadron/hyperon yields, including J/Psi meson production/suppression, strange matter formation, dileptons, and directed flow (bounce-off and squeeze-out) are investigated. Observations of interesting phenomena in dense matter are reported. However, we emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data. The role of future experiments with the STAR and ALICE detectors is pointed out.
Direct photon production in central Pb+Pb collisions at CERN-SPS energy is calculated within the relativistic microscopic transport model UrQMD, and within distinctly di erent versions of relativistic hydrodynamics. We find that in UrQMD the local momentum distributions of the secondaries are strongly elongated along the beam axis initially. Therefore, the preequilibrium contribution dominates the photon spectrum at transverse momenta above H 1.5 GeV. The hydrodynamics prediction of a strong correlation between the temperature and radial expansion velocities on the one hand and the slope of the transverse momentum distribution of direct photons on the other hand thus is not recovered in UrQMD. The rapidity distribution of direct photons in UrQMD reveals that the initial conditions for the longitudinal expansion of the photon source (the meson fluid ) resemble rather boostinvariance than Landau-like flow.
Dissociation rates of J / psi's with comoving mesons : thermal versus nonequilibrium scenario.
(1998)
We study J/psi dissociation processes in hadronic environments. The validity of a thermal meson gas ansatz is tested by confronting it with an alternative, nonequilibrium scenario. Heavy ion collisions are simulated in the frame- work of the microscopic transport model UrQMD, taking into account the production of charmonium states through hard parton-parton interactions and subsequent rescattering with hadrons. The thermal gas and microscopic transport scenarios are shown to be very dissimilar. Estimates of J/psi survival probabilities based on thermal models of comover interactions in heavy ion collisions are therefore not reliable.
A study of secondary Drell-Yan production in nuclear collisions is presented for SPS energies. In addition to the lepton pairs produced in the initial collisions of the projectile and target nucleons, we consider the potentially high dilepton yield from hard valence antiquarks in produced mesons and antibaryons. We calculate the secondary Drell-Yan contributions taking the collision spectrum of hadrons from the microscopic model URQMD. The con- tributions from meson-baryon interactions, small in hadron-nucleus interac- tions, are found to be substantial in nucleus-nucleus collisions at low dilepton masses. Preresonance collisions of partons may further increase the yields.
Charmonium production and absorption in heavy ion collisions is studied with the Ultrarelativisitic Quantum Molecular Dynamics model. We compare the scenario of universal and time independent color-octet dissociation cross sections with one of distinct color-singlet J/psi, psi 2 and CHIc states, evolving from small, color transparent configurations to their asymptotic sizes. The measured J/psi production cross sections in pA and AB collisions at SPS energies are consistent with both purely hadronic scenarios. The predicted rapidity dependence of J/psi suppression can be used to discriminate between the two experimentally. The importance of interactions with secondary hadrons and the applicability of thermal reaction kinetics to J/psi absorption are in- vestigated. We discuss the e ect of nuclear stopping and the role of leading hadrons. The dependence of the 2/J/psi ratio on the model assumptions and the possible influence of refeeding processes is also studied.
Crista junctions (CJs) are tubular invaginations of the inner membrane of mitochondria that connect the inner boundary with the cristae membrane. These architectural elements are critical for mitochondrial function. The yeast inner membrane protein Fcj1, called mitofilin in mammals, was reported to be preferentially located at CJs and crucial for their formation. Here we investigate the functional roles of individual domains of Fcj1. The most conserved part of Fcj1, the C-terminal domain, is essential for Fcj1 function. In its absence, formation of CJ is strongly impaired and irregular, and stacked cristae are present. This domain interacts with full-length Fcj1, suggesting a role in oligomer formation. It also interacts with Tob55 of the translocase of outer membrane β-barrel proteins (TOB)/sorting and assembly machinery (SAM) complex, which is required for the insertion of β-barrel proteins into the outer membrane. The association of the TOB/SAM complex with contact sites depends on the presence of Fcj1. The biogenesis of β-barrel proteins is not significantly affected in the absence of Fcj1. However, down-regulation of the TOB/SAM complex leads to altered cristae morphology and a moderate reduction in the number of CJs. We propose that the C-terminal domain of Fcj1 is critical for the interaction of Fcj1 with the TOB/SAM complex and thereby for stabilizing CJs in close proximity to the outer membrane. These results assign novel functions to both the C-terminal domain of Fcj1 and the TOB/SAM complex.
Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FO–ATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips.
Aim: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.
Results: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.
Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.
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.
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
(2018)
Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
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.
Using a microscopic transport model together with a coalescence after-burner, we study the formation of deuterons in Au + Au central collisions at s = 200 AGeV . It is found that the deuteron transverse momentum distributions are strongly a ected by the nucleon space-momentum correlations, at the moment of freeze-out, which are mostly determined by the number of rescatterings. This feature is useful for studying collision dynamics at ultrarelativistic energies.
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.
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. ...