Causal Modeling with Stationary Diffusions

We develop a novel approach towards causal inference. Rather than structural equations over a causal graph, we learn stochastic differential equations (SDEs) whose stationary densities model a system's behavior under interventions. These stationary diffusion models do not require the formalism of causal graphs, let alone the common assumption of acyclicity. We show that in several cases, they generalize to unseen interventions on their variables, often better than classical approaches. Our inference method is based on a new theoretical result that expresses a stationarity condition on the diffusion's generator in a reproducing kernel Hilbert space. The resulting kernel deviation from stationarity (KDS) is an objective function of independent interest

Entwicklung und Untersuchung eines einfachen klinischen Defizitscores für Schlaganfallpatienten als prädiktives Modell für das Outcome nach systemischer Thrombolyse

Die NIHSS ist der Goldstandard zur Beschreibung des Schlaganfallschweregrades. Die Anwendung der NIHSS setzt jedoch ein spezielles Training voraus. Für die Arbeit wurde ein einfacher Score entwickelt, der nur die Symptome Parese, Aphasie, Dysarthrie und Bewusstseinslage umfasst. Es wird nur das Vorliegen eines Symptoms bewertet, nicht dessen Ausprägung. Der prädiktive Wert des neuen Scores und der NIHSS für das klinische Outcome wurde an einer Stroke-Unit untersucht. Dabei zeigte sich, dass der neue Score eine zuverlässige Identifikation von Hirninfarktpatienten mit einer schlechten Behandlungsprognose ermöglicht. Die NIHSS ist nur geringfügig überlegen. Ein Anwendungsgebiet des neuen Scores sind klinische Studien, die eine Aufteilung von Patienten in Schwergradkategorien erfordern. Die einfache Handhabung des neuen Scores ermöglicht eine hohe Reliabilität der Bewertung auch bei vielen beteiligten Untersuchern, da die Bewertungskriterien leicht zu erlernen sind

Structure and function of claudins

AbstractClaudins are tetraspan transmembrane proteins of tight junctions. They determine the barrier properties of this type of cell–cell contact existing between the plasma membranes of two neighbouring cells, such as occurring in endothelia or epithelia. Claudins can completely tighten the paracellular cleft for solutes, and they can form paracellular ion pores. It is assumed that the extracellular loops specify these claudin functions. It is hypothesised that the larger first extracellular loop is critical for determining the paracellular tightness and the selective ion permeability. The shorter second extracellular loop may cause narrowing of the paracellular cleft and have a holding function between the opposing cell membranes. Sequence analysis of claudins has led to differentiation into two groups, designated as classic claudins (1–10, 14, 15, 17, 19) and non-classic claudins (11–13, 16, 18, 20–24), according to their degree of sequence similarity. This is also reflected in the derived sequence-structure function relationships for extracellular loops 1 and 2. The concepts evolved from these findings and first tentative molecular models for homophilic interactions may explain the different functional contribution of the two extracellular loops at tight junctions

Dense bottom gravity currents and their impact on pelagic methanotrophy at oxic/anoxic transition zones

We show that inflows of oxygenated waters into sulfidic layers have a strong impact on biogeochemical transformation at oxic/anoxic transition zones. Taking the pelagic methane dynamics in the Gotland Basin as an example, we performed our studies when one of the largest inflows ever recorded entered the Baltic Sea in March 2015. An inflowing gravity current transported oxic waters into the sulfidic deep layers and freshly generated a near-bottom secondary redox interface. At the upper slope, where the inflowing water masses were vigorously turbulent and the main and secondary redox interfaces in close contact to each other, methane oxidation rates inside the transition zone were found to be higher compared to the weakly turbulent basin interior. At the main redox interface in the basin center, lateral intrusions of oxygenated waters into intermediate water depth may have stimulated the growth of the methanotrophic community and their activity

Public-Private Partnership: Allheilmittel für die Finanzkrisen der öffentlichen Haushalte oder Risikofaktor?

Public Private Partnership (PPP) findet in Deutschland in den letzten Jahren immer mehr Verbreitung. Die Bandbreite für PPP-Projekte reicht von Bundesfernstraßen bis zu Schulen, Verwaltungsgebäuden, Krankenhäusern, Schwimmbädern etc. Führt dieses Modell zu einer Optimierung von Kosten und Erträgen oder stellt es einen Risikofaktor für den öffentlichen Sektor dar? Gerold Krause-Junk, Universität Hamburg, sieht darin vor allem einen Weg, den Konflikt zwischen "Effizienz- und Verteilungszielen" zu entschärfen: "Die allokative Aufgabe wird dann dem privaten bzw. einem weitgehend nach privatwirtschaftlichem Kalkül handelnden Anbieter überlassen; die Verteilungsaufgabe bleibt beim Staat ..." Für Frank Littwin, Finanzministerium des Landes Nordrhein-Westfalen, sind die PPP-Projekte kein Allheilmittel und auch kein wesentlicher Beitrag zur Haushaltskonsolidierung, sie führen aber zu deutlich mehr Kostentransparenz und befördern wirtschaftliches Handeln. Und nicht zuletzt sind sie ein wichtiges Instrument zur Verwaltungsmodernisierung. Dietrich Budäus und Birgit Grüb, Universität Hamburg, betonen, dass die Wirtschaftlichkeitsbeurteilung bei PPP-Projekten eine Reihe von Problemen aufwirft. Und für Lars P. Feld und Jan Schnellenbach, Universität Heidelberg, hängt die finanzpolitische Sinnhaftigkeit von PPP-Arrangements von den Details der Kooperation ab. Dabei sollte der öffentliche Sektor vor allem die langfristigen Folgekosten seiner Investitionen im Blick haben, wenn er die Zusammenarbeit mit den Privaten sucht.Public Private Partnership, Öffentlicher Sektor, Öffentlicher Haushalt, Finanzmarktkrise, Deutschland

Sensitive on-site detection of SARS-CoV-2 by ID NOW COVID-19

Point of care detection of SARS-CoV-2 is one pillar in a containment strategy and important to break infection chains. Here we report the sensitive, specific and robust detection of SARS-CoV-2 and respective variants of concern by the ID NOW COVID-19 device.Peer Reviewe

A strategy for enrichment of claudins based on their affinity to Clostridium perfringens enterotoxin

<p>Abstract</p> <p>Background</p> <p>Claudins, a family of protein localized in tight junctions, are essential for the control of paracellular permeation in epithelia and endothelia. The interaction of several claudins with <it>Clostridium perfringens </it>enterotoxin (CPE) has been exploited for an affinity-based enrichment of CPE-binding claudins from lysates of normal rat cholangiocytes.</p> <p>Results</p> <p>Immunoblotting and mass spectrometry (MS) experiments demonstrate strong enrichment of the CPE-binding claudins -3, -4 and -7, indicating specific association with glutathione-S-transferase (GST)-CPE_116–319fusion protein. In parallel, the co-elution of (non-CPE-binding) claudin-1 and claudin-5 was observed. The complete set of co-enriched proteins was identified by MS after electrophoretic separation. Relative mass spectrometric protein quantification with stable isotope labeling with amino acids in cell culture (SILAC) made it possible to discriminate specific binding from non-specific association to GST and/or matrix material.</p> <p>Conclusion</p> <p>CPE_116–319provides an efficient tool for single step enrichment of different claudins from cell lysates. Numerous proteins were shown to be co-enriched with the CPE-binding claudins, but there are no indications (except for claudins -1 and -5) for an association with tight junctions.</p

A Theoretical Interpretation of the Black Hole Fundamental Plane

We examine the origin and evolution of correlations between properties of supermassive black holes (BHs) and their host galaxies using simulations of major galaxy mergers, including the effects of gas dissipation, cooling, star formation, and BH accretion and feedback. We demonstrate that the simulations predict the existence of a BH 'fundamental plane' (BHFP), of the form M_BH sigma^(3.0+-0.3)*R_e^(0.43+-0.19) or M_BH M_bulge^(0.54+-0.17)*sigma^(2.2+-0.5), similar to relations found observationally. The simulations indicate that the BHFP can be understood roughly as a tilted intrinsic correlation between BH mass and spheroid binding energy, or the condition for feedback coupling to power a pressure-driven outflow. While changes in halo circular velocity, merger orbital parameters, progenitor disk redshifts and gas fractions, ISM gas pressurization, and other parameters can drive changes in e.g. sigma at fixed M_bulge, and therefore changes in the M_BH-sigma or M_BH-M_bulge relations, the BHFP is robust. Given the empirical trend of decreasing R_e for a given M_bulge at high redshift, the BHFP predicts that BHs will be more massive at fixed M_bulge, in good agreement with recent observations. This evolution in the structural properties of merger remnants, to smaller R_e and larger sigma (and therefore larger M_BH, conserving the BHFP) at a given M_bulge, is driven by the fact that bulge progenitors have characteristically larger gas fractions at high redshifts. Adopting the observed evolution of disk gas fractions with redshift, our simulations predict the observed trends in both R_e(M_bulge) and M_BH(M_bulge).Comment: 22 pages, 19 figures, replaced with version accepted to ApJ. Companion paper to arXiv:0707.400

Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients

Background: A novel gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) has been recently identified and found to have a prevalence of 40% in prostate tumor samples from American patients carrying a homozygous R462Q mutation in the RNaseL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. Here, we attempt to measure the prevalence of XMRV in prostate cancer cases in Germany and determine whether an analogous association with the R462Q polymorphism exists. Results: 589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies. Conclusion: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections

Proteome analysis of the HIV-1 Gag interactome

AbstractHuman immunodeficiency virus Gag drives assembly of virions in infected cells and interacts with host factors which facilitate or restrict viral replication. Although several Gag-binding proteins have been characterized, understanding of virus–host interactions remains incomplete. In a series of six affinity purification screens, we have identified protein candidates for interaction with HIV-1 Gag. Proteins previously found in virions or identified in siRNA screens for host factors influencing HIV-1 replication were recovered. Helicases, translation factors, cytoskeletal and motor proteins, factors involved in RNA degradation and RNA interference were enriched in the interaction data. Cellular networks of cytoskeleton, SR proteins and tRNA synthetases were identified. Most prominently, components of cytoplasmic RNA transport granules were co-purified with Gag. This study provides a survey of known Gag–host interactions and identifies novel Gag binding candidates. These factors are associated with distinct molecular functions and cellular pathways relevant in host–pathogen interactions