Entwicklung innovativer nicht-viraler Vektoren zur Gentherapie

In der vorliegenden Arbeit wurde ein innovativer Vektor zum Gentransfer entwickelt. Im Unterschied zu dem synthetischen Polyethylenimin als Goldstandard polymerer Vektoren war das Ziel die Entwicklung eines natürlichen, biokompatiblen und bioabbaubaren Vektors. Dieser sollte einfach zu modifizieren sein und sich für die Anwendung als Trägersystem für Nukleinsäuren in seinen Eigenschaften maßgeschneidert anpassen lassen.This work dealt with the development of an innovative vector for gene delivery. In difference to synthetic polyethylenimine as gold standard of polymeric vectors for gene delivery the design of a natural, biocompatible and biodegradable vector was to be achieved. Additionally the vector should be easy to modify to facilitate a tailor made adjustment of his characteristics

Soil moisture droughts in Germany: retrospective analysis, parametric uncertainty, and monitoring

Droughts are worldwide the second most severe natural disaster beside floods. In Europe, droughts are the costliest natural disasters with average expenses of 621 million EUR per event. The last severe drought event took place in 2003. It induced an agro-economic loss of 1.5 billion EUR in Germany alone. Such economical losses emphasize the need of an operational system for monitoring agricultural droughts in order to mitigate their negative consequences. Observation-based monitoring of agricultural droughts, which are characterized by soil moisture deficits, is technically and economically not feasible on regional to national scales. Hydrologic modeling is the prime alternative to estimate soil moisture availability on large spatial domains. Such models are driven by meteorological observations and predict hydrological fluxes and states, such as soil moisture or evapotranspiration. Predictions of hydrologic models underlie several sources of uncertainties. These uncertainties arise from input data, model structure, initial conditions, and model parameters. The implications of parametric uncertainty to hydrologic predictions are analyzed herein. The main objective of this work is to develop a monitoring system for agricultural droughts in Germany. The development of such a system includes several challenges. First, a spatially continuous dataset of soil moisture for entire Germany is derived from modeling. The parametric uncertainty of such hydrologic predictions is taken into account. Second, the propagation of parametric uncertainty of soil moisture to the identification of drought characteristics is estimated in order to evaluate the uncertainty inherent to such a monitoring system. Third, an approach to reduce the parametric uncertainty by using satellite retrieved land surface temperature data is investigated. And forth, an operational system providing drought information in near-real time is developed and implemented

Sunitinib Inhibits Cell Proliferation and Alters Steroidogenesis by Down-Regulation of HSD3B2 in Adrenocortical Carcinoma Cells

The multi-tyrosine kinase inhibitor sunitinib is used in the treatment of several solid tumors. Animal experiments pointed to an adrenotoxic effect of sunitinib. Therefore, we evaluated the expression of key targets of sunitinib in human adrenocortical carcinoma (ACC) tumor samples and investigated its in vitro effects in ACC cell lines. We carried out immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptor (VEGF-R2) in 157 ACC samples and nine normal adrenal glands. VEGF and VEGF-R2 protein were expressed in 72 and 99% of ACC samples, respectively. Using NCI-H295 and SW13 ACC cell lines, we investigated the effects of sunitinib on cell proliferation. Sunitinib reduced dose-dependently cell viability of both NCI-H295 and SW13 cells (SW13: 0.1 μM 96 ± 7%, 1 μM 90 ± 9%*, 5 μM 62 ± 6%*, controls 100 ± 9%; *p < 0.05). To determine sunitinib effects on steroidogenesis, we measured steroid hormones in cell culture supernatant by gas chromatography–mass spectrometry. We observed a pronounced decrease of cortisol secretion (1 μM 90.1 ± 1.5%*, 5 μM 57.2 ± 0.3%*, controls 100 ± 2.4%) and a concomitant increase in the DHEA/4-androstenedione and 17-hydroxypregnenolone/17-hydroxyprogesterone ratios, indicating specific inhibition of 3β-hydroxysteroid dehydrogenase (HSD3B2). In yeast microsomes transformed with HSD3B2, no direct inhibition of HSD3B2 by sunitinib was detected. Sunitinib induced down-regulation of HSD3B2 mRNA and protein in ACC cell lines (mRNA: 1 μM 44 ± 16%*; 5 μM 22 ± 2%*; 10 μM 19 ± 4%*; protein: 1 μM 82 ± 8%; 5 μM 63 ± 8%*; 10 μM 55 ± 9%*). CYP11B1 was down-regulated at mRNA but not at protein level and CYP11A1 remained unchanged. In conclusion, target molecules of sunitinib are expressed in the vast majority of ACC samples. Sunitinib exhibits anti-proliferative effects in vitro, and appears to specifically block adrenal steroidogenesis by down-regulation of HSD3B2, rendering it a promising option for treatment of ACC

Acute Changes in P-Wave Morphology by Pulmonary Vein Isolation in Atrial Fibrillation Patients

International audiencePulmonary vein (PV) plays an important role in atrial fibrillation (AF) initiation, progression, and stability. Successful PV isolation (PVI), either by radiofrequency catheter or Cryoballoon ablation, may terminate AF and prevent its recurrence. Whereas, incomplete PV isolation or reconnection of isolated PVs underlies mechanisms of AF recurrence. Hence, defining parameters able to predict a successful PVI and detect reconnections can assist clinicians in treatment of AF patients. Here, we developed a highly detailed human atrial model to simulate PVI and its acute effect on the P-wave morphology. Afterwards, the simulation results were compared and validated by recorded ECGs from patients before and after PVI procedure. In both simulation data and clinical recordings, we observed morphological changes in P-wave after PVI. More importantly our simulation helped us to find electrode positions in which the differences in P-wave morphology before and after PVI were more pronounced

A framework for regional smart energy planning using volunteered geographic information

peer reviewedThis study presents a framework for regional smart energy planning for the optimal location and sizing of small hybrid systems. By using an optimization model - in combination with weather data - various local energy systems are simulated using the Calliope and PyPSA energy system simulation tools. The optimization and simulation models are fed with GIS data from different volunteered geographic information projects, including OpenStreetMap. These allow automatic allocation of specific demand profiles to diverse OpenStreetMap building categories. Moreover, based on the characteristics of the OpenStreetMap data, a set of possible distributed energy resources, including renewables and fossil-fueled generators, is defined for each building category. The optimization model can be applied for a set of scenarios based on different assumptions on electricity prices and technologies. Moreover, to assess the impact of the scenarios on the current distribution infrastructure, a simulation model of the low- and medium-voltage network is conducted. Finally, to facilitate their dissemination, the results of the simulation are stored in a PostgreSQL database, before they are delivered by a RESTful Laravel Server and displayed in an angular web application

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery

Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XTTM). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF

Excited-State Interaction of Semiconducting Single-Walled Carbon Nanotubes with Their Wrapping Polymers

We employ photoluminescence and pump–probe spectroscopy on films of semiconducting single-walled carbon nanotubes (CNTs) of different chirality wrapped with either a wide band gap polyfluorene derivative (PF12) or a polythiophene with narrower gap (P3DDT) to elucidate the excited states’ interplay between the two materials. Excitation above the polymer band gap gives way to an ultrafast electron transfer from both polymers toward the CNTs. By monitoring the hole polaron on the polymer via its mid infrared signature, we show that also illumination below the polymer band gap leads to the formation of this fingerprint and infer that holes are also transferred toward the polymer. As this contradicts the standard way of discussing the involved energy levels, we propose that polymer-wrapped CNTs should be considered as a single hybrid system, exhibiting states shared between the two components. This proposition is validated through quantum chemical calculations that show hybridization of the first excited states, especially for the thiophene–CNT sample

HESS Opinions: Science in today's media landscape – challenges and lessons from hydrologists and journalists

Media such as television, newspapers and social media play a key role in the communication between scientists and the general public. Communicating your science via the media can be positive and rewarding by providing the inherent joy of sharing your knowledge with a broader audience, promoting science as a fundamental part of culture and society, impacting decision and policy makers, and giving you a greater recognition by institutions, colleagues and funders. However, the interaction between scientists and journalists is not always straightforward. For instance, scientists may not always be able to translate their work into a compelling story, and journalists may sometimes misinterpret scientific output. In this paper, we present insights from hydrologists and journalists discussing the advantages and benefits as well as the potential pitfalls and aftermath of science-media interaction. As we perceive interacting with the media as a rewarding and essential part of our work, we aim to encourage scientists to participate in the diverse and evolving media landscape. With this paper, we call on the scientific community to support scientists who actively contribute to a fruitful science-media relationship