Identifizierung der endothelspezifischen Rezeptor-Protein-Tyrosinphosphatase VE-PTP als VE-Cadherin-Ligand

Die Zell-Zell-Kontakte von Endothelzellen sind für die Aufrechterhaltung der Barriere zwischen dem Blutgefäßsystem und dem umliegenden Gewebe verantwortlich. VE-Cadherin ist das essentielle Zell-Adhäsionsmolekül der zonula adherentes in Endothelzellen. Veränderungen der Zell-Zell-Kontakte von Endothelzellen korrelieren häufig mit einer Tyrosinphosphorylierung von VE-Cadherin. In dieser Arbeit konnte gezeigt werden, dass die endothelspezifische Rezeptor-Protein-Tyrosinphosphatase VE-PTP (vascular endothelial-protein tyrosine phosphatase) mit VE-Cadherin co-präzipitiert wird. Diese Interaktion wird über die fünfte Cadherindomäne von VE-Cadherin und der membranproximalen, extrazellulären 17. Fibronektin-III-Domäne von VE-PTP vermittelt. In COS-7 Zellen führt die Co-transfektion von VE-Cadherin und VEGFR-2 (Flk-1) zu einer Tyrosinphosphorylierung von VE-Cadherin. Diese Phosphorylierung wird durch die zusätzliche Transfektion der katalytisch aktiven, jedoch nicht durch die Transfektion einer katalytisch inaktiven VE-PTP inhibiert

Improved estimation of Fokker-Planck equations through optimisation

An improved method for the description of hierarchical complex systems by means of a Fokker-Planck equation is presented. In particular the limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm for constraint problems (L-BFGS-B) is used to minimize the distance between the numerical solutions of the Fokker-Planck equation and the empirical probability density functions and thus to estimate properly the drift and diffusion term of the Fokker-Planck equation. The optimisation routine is applied to a time series of velocity measurements obtained from a turbulent helium gas jet in order to demonstrate the benefits and to quantify the improvements of this new optimisation routine

An Iterative Procedure for the Estimation of Drift and Diffusion Coefficients of Langevin Processes

A general method is proposed which allows one to estimate drift and diffusion coefficients of a stochastic process governed by a Langevin equation. It extends a previously devised approach [R. Friedrich et al., Physics Letters A 271, 217 (2000)], which requires sufficiently high sampling rates. The analysis is based on an iterative procedure minimizing the Kullback-Leibler distance between measured and estimated two time joint probability distributions of the process.Comment: 4 pages, 5 figure

From short to fat tails in financial markets: A unified description

In complex systems such as turbulent flows and financial markets, the dynamics in long and short time-lags, signaled by Gaussian and fat-tailed statistics, respectively, calls for a unified description. To address this issue we analyze a real dataset, namely, price fluctuations, in a wide range of temporal scales to embrace both regimes. By means of Kramers-Moyal (KM) coefficients evaluated from empirical time series, we obtain the evolution equation for the probability density function (PDF) of price returns. We also present consistent asymptotic solutions for the timescale dependent equation that emerges from the empirical analysis. From these solutions, new relationships connecting PDF characteristics, such as tail exponents, to parameters of KM coefficients arise. The results reveal a dynamical path that leads from Gaussian to fat-tailed statistics, furnishing insights on other complex systems where akin crossover is observed.Comment: 11 pages, 5 figure

A multi-centre randomised controlled study of pre-IVF outpatient hysteroscopy in women with recurrent IVF implantation failure: Trial of Outpatient Hysteroscopy - [TROPHY] in IVF

<p>Abstract</p> <p>Background</p> <p>The success rate of IVF treatment is low. A recent systematic review and meta-analysis found that the outcome of IVF treatment could be improved in patients who have experienced recurrent implantation failure if an outpatient hysteroscopy (OH) is performed before starting the new treatment cycle. However, the trials were of variable quality, leading to a call for a large and high-quality randomised trial. This protocol describes a multi-centre randomised controlled trial to test the hypothesis that performing an OH prior to starting an IVF cycle improves the live birth rate of the subsequent IVF cycle in women who have experienced two to four failed IVF cycles.</p> <p>Methods and design</p> <p>Eligible and consenting women will be randomised to either OH or no OH using an internet based trial management programme that ensures allocation concealment and employs minimisation for important stratification variables including age, body mass index, basal follicle stimulating hormone level and number of previous failed IVF cycles. The primary outcome is live birth rate per IVF cycle started. Other outcomes include implantation, clinical pregnancy and miscarriage rates.</p> <p>The sample size for this study has been estimated as 758 participants with 379 participants in each arm. Interim analysis will be conducted by an independent Data Monitoring Committee (DMC), and final analysis will be by intention to treat. A favourable ethical opinion has been obtained (REC reference: 09/H0804/32).</p> <p>Trail Registration</p> <p>The trial has been assigned the following ISRCTN number: ISRCTN35859078</p

The role of cat eye narrowing movements in cat–human communication

Domestic animals are sensitive to human cues that facilitate inter-specific communication, including cues to emotional state. The eyes are important in signalling emotions, with the act of narrowing the eyes appearing to be associated with positive emotional communication in a range of species. This study examines the communicatory significance of a widely reported cat behaviour that involves eye narrowing, referred to as the slow blink sequence. Slow blink sequences typically involve a series of half-blinks followed by either a prolonged eye narrow or an eye closure. Our first experiment revealed that cat half-blinks and eye narrowing occurred more frequently in response to owners’ slow blink stimuli towards their cats (compared to no owner–cat interaction). In a second experiment, this time where an experimenter provided the slow blink stimulus, cats had a higher propensity to approach the experimenter after a slow blink interaction than when they had adopted a neutral expression. Collectively, our results suggest that slow blink sequences may function as a form of positive emotional communication between cats and humans

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell–cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.United States. Army Research Office. Institute for Soldier NanotechnologiesNational Institutes of Health (U.S.) (HL092836)National Institutes of Health (U.S.) (EB02597)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL099073)National Science Foundation (U.S.) (DMR0847287)United States. Office of Naval Research (ONR PECASE Award)United States. Office of Naval Research (Young Investigator award)National Research Foundation of Korea (grant (NRF-2010-220-D00014)

Determination of Interleukin-6 and Tumor Necrosis Factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia

BACKGROUND: Our objective was to determine the role of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha), markers of immune activation and endothelial dysfunction, in patients with preeclampsia. METHODS: Twenty four women with preeclampsia and eighteen antepartum normotensive pregnant women were recruited as controls. Serum levels of IL-6 and TNF-alpha were measured by enzyme-linked immunosorbent assay. We used independent-samples t test to assess the differences in the concentration of cytokines in preeclamptic patients and control subjects. RESULTS: IL-6 levels [mean (S.D.)] were significantly higher in preeclamptic women [5.8 (4.85) pg/ml] compared to normal pregnant women [3.01 (2.45) pg/ml] (p = 0.02). There was no significant change in concentration of TNF-alpha in preeclamptic women [53.8 (30.0) pg/ml] compared to normal pregnant women [51.9 (33.8) pg/ml] (p > 0.1). CONCLUSION: The results of this study show that IL-6 as a pro-inflammatory cytokine is present in higher concentration in women with preeclampsia. The study was undertaken in women with established preeclampsia and it is not possible to determine whether the increased concentration of IL-6 is a cause or consequence of the disease. Furthermore, these findings suggest that serum TNF-alpha level is not associated with preeclampsia