New Approaches for ab initio Calculations of Molecules with Strong Electron Correlation

Reliable quantum chemical methods for the description of molecules with dense-lying frontier orbitals are needed in the context of many chemical compounds and reactions. Here, we review developments that led to our newcomputational toolbo x which implements the quantum chemical density matrix renormalization group in a second-generation algorithm. We present an overview of the different components of this toolbox.Comment: 19 pages, 1 tabl

Einführung in die empirische Sozialforschung I: Skript

Bei dem vorliegenden Text handelt es sich um die überarbeitete und aktualisierte sechste Auflage des Skriptes zur "Einführung in die sozialwissenschaftlichen Methoden und ihre Anwendung in empirischen Untersuchungen I" aus dem Jahr 1999, allerdings mit neuer Überschrift: "Einführung in die empirische Sozialforschung". Die Überarbeitung bezieht sich insbesondere auf die erforderliche Aktualisierung in Folge neuerer Entwicklungen von Auswahl- und Befragungsmethoden sowie der Netzwerkanalyse. Außerdem wird die zwischenzeitlich erschienene Methodenliteratur berücksichtigt. Der diesem Skript zugrunde liegende Stoff bezieht sich auf den ersten Teil der auf zwei Semester angelegten "Einführung in die empirische Sozialforschung" im Bachelorstudiengang "Sozialökonomik". Es geht darum, z. T. aufbauend auf den Veranstaltungen zur Einführung in die Soziologie, mit jenem Forschungsinstrumentarium vertraut zu machen, das in der Soziologie für Fragen von Exploration, Deskription und Analyse sozialer Gegebenheiten zur Verfügung steht. Im Zentrum stehen - neben der Erörterung eher wissenschafts- und messtheoretischer Probleme - grundlegende Methoden der Datenerhebung und Auswahlverfahren. Sie werden ergänzt durch die Vorstellung spezieller Formen der Datenerhebung sowie ausgewählter Untersuchungsformen. (ICD2

Human Subtilase SKI-1/S1P Is a Master Regulator of the HCV Lifecycle and a Potential Host Cell Target for Developing Indirect-Acting Antiviral Agents

HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV), whose assembly and pathogenesis depend on interaction with lipid droplets (LDs). One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1) – or site-1 protease (S1P). SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs), which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP)/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow development of novel broad-spectrum biopharmaceuticals that could lead to novel indirect-acting antiviral options with the current standard of care

Gesundheit und Wohlbefinden von Kindern und Jugendlichen in St. Leonhard und Schweinau: Befunde aus einem Lehrforschungsprojekt in Nürnberg

"Der vorliegende Bericht enthält Ergebnisse aus einem im Studienjahr 2008/09 durchgeführten Lehrforschungsprojekt über die Lebensqualität von Kindern und Jugendlichen in zwei sozialstrukturell und -ökologisch benachteiligten Stadtteilen Nürnbergs. Im Vordergrund stehen dabei schriftliche Befragungen von SchülerInnen und Eltern über Gesundheit und Wohlbefinden. Die damit erhobenen Daten für n=924 Grund- und Hauptschulkinder werden vorwiegend nach Schulform und Geschlechtszugehörigkeit analysiert. Darüber hinaus steht die Berichterstattung der in Nürnberg erscheinenden Presse über die beiden Stadtteile St. Leonhard und Schweinau im Fokus. Schließlich wird netzwerkanalytisch der Frage nachgegangen, ob, und wenn ja, inwieweit die in den Stadtteilen agierenden sozialen Einrichtungen untereinander kooperieren." (Autorenreferat

Evaluationsbericht ARIADNEmed: Ergebnisse zur Pilotphase des Mentoring-Programms für Nachwuchswissenschaftlerinnen an der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg

"Der vorliegende Bericht stellt die Ergebnisse der Evaluation der Pilotphase des ARIADNEmed-Mentoring-Programms der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg vor. Dieses erste Mentoring-Programm für promovierte Wissenschaftlerinnen an der Medizinischen Fakultät begann am 24. Juni 2008 mit einer Einführungsveranstaltung. Seitdem begleiteten 47 habilitierte WissenschaftlerInnen und ProfessorInnen insgesamt 48 Nachwuchswissenschaftlerinnen aus verschiedenen Bereichen der Medizinischen Fakultät auf deren Weg in Richtung Habilitation, unterstützt von einem Rahmenprogramm, das die Mentoringpartnerbeziehungen begleitete und sie optimieren sollte. Die Abschlussveranstaltung der Pilotphase fand am 30. November 2009 statt. Die nachfolgenden Ausführungen geben einen Einblick in das Programm und seine Ausgestaltung. Im Mittelpunkt steht allerdings die Darstellung der Ergebnisse dreier Befragungen aller 95 Beteiligten zum Rahmenprogramm und zur eingegangenen Mentoringbeziehung sowie zu ihren Erwartungen an das Programm und zu ihrer Bewertung der Realisierung des Programms." (Textauszug

Microbiota of the Gut-Lymph Node Axis: Depletion of Mucosa-Associated Segmented Filamentous Bacteria and Enrichment of Methanobrevibacter by Colistin Sulfate and Linco-Spectin in Pigs

Microorganisms are translocated from the gut to lymphatic tissues via immune cells, thereby challenging and training the mammalian immune system. Antibiotics alter the gut microbiome and consecutively might also affect the corresponding translocation processes, resulting in an imbalanced state between the intestinal microbiota and the host. Hence, understanding the variant effects of antibiotics on the microbiome of gut-associated tissues is of vital importance for maintaining metabolic homeostasis and animal health. In the present study, we analyzed the microbiome of (i) pig feces, ileum, and ileocecal lymph nodes under the influence of antibiotics (Linco-Spectin and Colistin sulfate) using 16S rRNA gene sequencing for high-resolution community profiling and (ii) ileocecal lymph nodes in more detail with two additional methodological approaches, i.e., cultivation of ileocecal lymph node samples and (iii) metatranscriptome sequencing of a single lymph node sample. Supplementation of medicated feed showed a local effect on feces and ileal mucosa-associated microbiomes. Pigs that received antibiotics harbored significantly reduced amounts of segmented filamentous bacteria (SFB) along the ileal mucosa (p = 0.048; 199.17-fold change) and increased amounts of Methanobrevibacter, a methanogenic Euryarchaeote in fecal samples (p = 0.005; 20.17-fold change) compared to the control group. Analysis of the porcine ileocecal lymph node microbiome exposed large differences between the viable and the dead fraction of microorganisms and the microbiome was altered to a lesser extent by antibiotics compared with feces and ileum. The core microbiome of lymph nodes was constituted mainly of Proteobacteria. RNA-sequencing of a single lymph node sample unveiled transcripts responsible for amino acid and carbohydrate metabolism as well as protein turnover, DNA replication and signal transduction. The study presented here is the first comparative study of microbial communities in feces, ileum, and its associated ileocecal lymph nodes. In each analyzed site, we identified specific phylotypes susceptible to antibiotic treatment that can have profound impacts on the host physiological and immunological state, or even on global biogeochemical cycles. Our results indicate that pathogenic bacteria, e.g., enteropathogenic Escherichia coli, could escape antibiotic treatment by translocating to lymph nodes. In general ileocecal lymph nodes harbor a more diverse and active community of microorganisms than previously assumed

ARResT/Interrogate: an interactive immunoprofiler for IG/TR NGS data.

Abstract Motivation The study of immunoglobulins and T cell receptors using next-generation sequencing has finally allowed exploring immune repertoires and responses in their immense variability and complexity. Unsurprisingly, their analysis and interpretation is a highly convoluted task. Results We thus implemented ARResT/Interrogate, a web-based, interactive application. It can organize and filter large amounts of immunogenetic data by numerous criteria, calculate several relevant statistics, and present results in the form of multiple interconnected visualizations. Availability and Implementation ARResT/Interrogate is implemented primarily in R, and is freely available at http://bat.infspire.org/arrest/interrogate/ Supplementary information Supplementary data are available at Bioinformatics online

Improved X-ray detection and particle identification with avalanche photodiodes

Avalanche photodiodes are commonly used as detectors for low energy x-rays. In this work we report on a fitting technique used to account for different detector responses resulting from photo absorption in the various APD layers. The use of this technique results in an improvement of the energy resolution at 8.2 keV by up to a factor of 2, and corrects the timing information by up to 25 ns to account for space dependent electron drift time. In addition, this waveform analysis is used for particle identification, e.g. to distinguish between x-rays and MeV electrons in our experiment.Comment: 6 pages, 6 figure

Size and shape dependent photoluminescence and excited state decay rates of diamondoids

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.We present photoluminescence spectra and excited state decay rates of a series of diamondoids, which represent molecular structural analogues to hydrogen-passivated bulk diamond. Specific isomers of the five smallest diamondoids (adamantane–pentamantane) have been brought into the gas phase and irradiated with synchrotron radiation. All investigated compounds show intrinsic photoluminescence in the ultraviolet spectral region. The emission spectra exhibit pronounced vibrational fine structure which is analyzed using quantum chemical calculations. We show that the geometrical relaxation of the first excited state of adamantane, exhibiting Rydberg character, leads to the loss of Td symmetry. The luminescence of adamantane is attributed to a transition from the delocalized first excited state into different vibrational modes of the electronic ground state. Similar geometrical changes of the excited state structure have also been identified in the other investigated diamondoids. The excited state decay rates show a clear dependence on the size of the diamondoid, but are independent of the particle geometry, further indicating a loss of particle symmetry upon electronic excitation.DFG, FOR 1282, Controlling the electronic structure of semiconductor nanoparticles by doping and hybrid formatio

Association of pulmonary vein isolation and major cardiovascular events in patients with atrial fibrillation.

BACKGROUND Patients with atrial fibrillation (AF) face an increased risk of adverse cardiovascular events. Evidence suggests that early rhythm control including AF ablation may reduce this risk. METHODS To compare the risks for cardiovascular events in AF patients with and without pulmonary vein isolation (PVI), we analysed data from two prospective cohort studies in Switzerland (n = 3968). A total of 325 patients who had undergone PVI during a 1-year observational period were assigned to the PVI group. Using coarsened exact matching, 2193 patients were assigned to the non-PVI group. Outcomes were all-cause mortality, hospital admission for acute heart failure, a composite of stroke, transient ischemic attack and systemic embolism (Stroke/TIA/SE), myocardial infarction (MI), and bleedings. We calculated multivariable adjusted Cox proportional-hazards models. RESULTS Overall, 2518 patients were included, median age was 66 years [IQR 61.0, 71.0], 25.8% were female. After a median follow-up time of 3.9 years, fewer patients in the PVI group died from any cause (incidence per 100 patient-years 0.64 versus 1.87, HR 0.39, 95%CI 0.19-0.79, p = 0.009) or were admitted to hospital for acute heart failure (incidence per 100 patient-years 0.52 versus 1.72, HR 0.44, 95%CI 0.21-0.95, p = 0.035). There was no significant association between PVI and Stroke/TIA/SE (HR 0.94, 95%CI 0.52-1.69, p = 0.80), MI (HR 0.43, 95%CI 0.11-1.63, p = 0.20) or bleeding (HR 0.75, 95% CI 0.50-1.12, p = 0.20). CONCLUSIONS In our matched comparison, patients in the PVI group had a lower incidence rate of all-cause mortality and hospital admission for acute heart failure compared to the non-PVI group. CLINICALTRIALS GOV IDENTIFIER NCT02105844, April 7th 2014