Biochemische und pharmakokinetische Charakterisierung zweier Varianten eines neuen, auf Dipetalogastin II basierenden, chimären Thrombininhibitors

Hirudin und Dipetalogastin II sind hochpotente, natürliche Thrombininhibitoren, die in der Therapie kardiovaskulärer Erkrankungen als auch in der Tumortherapie potentielle Einsatzgebiete aufweisen. In dieser Arbeit wurden zwei Varianten eines neuen, chimären Thrombininhibitors auf der Basis dieser beiden Inhibitoren charakterisiert. Beide Inhibitorvarianten wiesen eine starke Thrombinhemmung auf, wobei Variante 1 eine slow, tight-binding und Variante 2 eine klassisch kompetitive Inhibitionskinetik präsentierte

Central Sleep Apnea in Patients due to Severe Aortic Stenosis

History. We report about the course of central sleep apnea (CSA) in 3 patients (70.3 ± 15.2 years) with severe aortic stenosis (AS) (AVA ≤ 1.0 cm2, NYHA 2.7 ± 1.4). Investigations. Every patient received echocardiography, left/right-heart catheterization, and cardiorespiratory polygraphy before and 6 months after surgical aortic valve replacement (without right-heart catheterization during follow up). Course. Preoperatively all patients demonstrated reduced systolic left ventricular function (EF <55%). They had elevated pulmoraryarterialy pressures and severe CSA. After valve replacement left ventricular function and exercise capacity improved, as well as the severity of CSA. Conclusion. Patients with severe AS can develop CSA, which seems to improve after surgery. Patients with severe AS should be screened for CSA, because CSA might be an additional risk factor and hint that myocardial adaptation is exhausting

Extracorporeal Cardiac Shock Wave Therapy Ameliorates Clinical Symptoms and Improves Regional Myocardial Blood Flow in a Patient with Severe Coronary Artery Disease and Refractory Angina

Different therapeutic options are being used for chronic coronary artery disease (CAD). We report about a 51-year-old female with CAD and refractory angina pectoris despite maximally tolerated medical therapy and after both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The patient received cardiac shock wave therapy (CSWT) over a period of 6 month. There was no arrhythmia during or after treatment; enzyme levels were normal at all times. PET imaging showed a substantial improvement of myocardial stress perfusion. Since the patient reported that she now was fully capable to deal with her everyday life, further treatment options were postponed. Our case report suggests that ultrasound-guided CSWT is able to improve symptoms and perfusion in ischemic myocardium

Big Data - An Interdisciplinary Opportunity for Information Systems Research

“Big data” describes technologies that promise to fulfill a fundamental tenet of research in information systems, which is to provide the right information to the right receiver in the right volume and quality at the right time. For information systems research as an application-oriented research discipline, opportunities, and risks arise from using big data. Risks arise primarily from the considerable number of resources used for the explanation and design of fads. Opportunities arise because these resources lead to substantial knowledge gains, which support scientific progress within the discipline and are of relevance to practice as well. From the authors’ perspective, information systems research is ideally positioned to support big data critically and use the knowledge gained to explain and design innovative information systems in business and administration – regardless of whether big data is in reality a disruptive technology or a cursory fad. The continuing development and adoption of big data will ultimately provide clarity on whether big data is a fad or if it represents substantial progress in information systems research. Three theses also show how future technological developments can be used to advance the discipline of information systems. Technological progress should be used for a cumulative supplement of existing models, tools, and methods. By contrast, scientific revolutions are independent of technological progress

Social network analysis for technology-enhanced learning: review and future directions

Sie, R. L. L., Ullmann, T. D., Rajagopal, K., Cela, K., Bitter-Rijpkema, M., & Sloep, P. B. (2012). Social network analysis for technology-enhanced learning: review and future directions. International Journal of Technology Enhanced Learning, 4(3/4), 172-190.By nature, learning is social. The interactions by which we learn from others inherently form a network of relationships among people, but also between people and resources. This paper gives an overview of the potential social network analysis (SNA) may have for social learning. It starts with an overview of the history of social learning and how SNA may be of value. The core of the paper outlines the state-of-art of SNA for technology-enhanced learning (TEL), by means of four possible types of SNA applications: visualisation, analysis, simulation, and interventions. In an outlook, future directions of SNA research for TEL are provided

In situ airborne measurements of atmospheric and sea surface parameters related to offshore wind parks in the German Bight

Between 6 September 2016 and 15 October 2017, meteorological measurement flights were conducted above the German Bight in the framework of the project WIPAFF (Wind Park Far Field). The scope of the measurements was to study long-range wakes with an extent larger than 10 km behind entire wind parks, and to investigate the interaction of wind parks and the marine atmospheric boundary layer. The research aircraft Dornier 128 of the Technische Universität (TU) Braunschweig performed in total 41 measurement flights during different seasons and different stability conditions. The instrumentation consisted of a nose boom with sensors for measuring the wind vector, temperature and humidity, and additionally sensors for characterizing the water surface, a surface temperature sensor, a laser scanner and two cameras in the visible and infrared wavelength range. A detailed overview of the aircraft, sensors, data post-processing and flight patterns is provided here. Further, averaged profiles of atmospheric parameters illustrate the range of conditions. The potential use of the data set has been shown already by first publications. The data are publicly available in the world data centre PANGAEA (https://doi.org/10.1594/PANGAEA.902845; Bärfuss et al., 2019a)

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary.

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007-30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan-Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181-242 days), which was statistically significantly different compared to patients treated with the rest of the medications: olanzapine (136 days, 95%CI:121-153 days), aripiprazole (102 days, 95%CI:81-126 days), ziprasidone (93 days, 95%CI:82-119 days), quetiapine (89 days, 95%CI:81-100 days), clozapine (76 days, 95%CI:54-92 days), amisulpride (73 days, 95%CI:62-85 days), and risperidone (55 days, 95%CI: 41-63 days). Our results in Hungary are partly similar to those of a recent register-based study in Finland with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006, 2011); namely the median times to all-cause medication discontinuation were <120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order

Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator

The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion