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Das Kernanliegen des Datenschutzes ist es, natürliche Personen vor nachteiligen Effekten der Speicherung und Verarbeitung der sie betreffenden Daten zu schützen. Aber viele Personen scheinen gar nicht geschützt werden zu wollen. Im Gegenteil, viele Endanwender willigen “freiwillig“ – bewusst oder unbewusst – in eine umfassende Verarbeitung ihrer personenbezogenen Daten ein. Warum tun Menschen dies? Es werden verschiedene Ursachen diskutiert (beispielsweise in [79]), hierzu gehören Uninformiertheit, mangelnde Sensibilität, das Gefühl der Hilflosigkeit, mangelnde Zahlungsbereitschaft und mangelnde Alternativen. Auch wenn dies in Einzelfällen zutrifft, so gibt es oft sehr wohl datenschutzfreundliche Alternativen. Beispielsweise existiert zu WhatsApp (als Instant Messaging App) die Alternative Threema. Threema gilt als EU-DS-GVO-konform und funktional durchaus mit WhatsApp vergleichbar [62]. Allerdings ist inzwischen die aktuelle Netzwerkgröße ein entscheidendes Auswahlkriterium: Im Januar 2018 hatte Threema 4,5 Millionen Nutzer [172], WhatsApp dagegen 1,5 Milliarden [171]. Dies ist ein Indiz dafür, dass WhatsApp sich quasi zum De-facto-Standard entwickelt hat und es für die einzelne Person nur schwer möglich ist, viele andere “zum Wechsel auf ein anderes Produkt zu bewegen. [. . . ] Bei Diensten mit Nutzerzahlen im Milliardenbereich kann von ’Freiwilligkeit’ nur noch bedingt gesprochen werden.“ [9]
The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells
(2012)
BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H(2) S) on Na(+) absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H(2)S were further investigated on Na(+) channels expressed in Xenopus oocytes and Na(+) /K(+)-ATPase activity in vitro. Membrane abundance of Na(+) /K(+)-ATPase was determined by surface biotinylation and Western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca(2+) concentrations were measured with Fura-2. KEY RESULTS H(2)S rapidly and reversibly inhibited Na(+) transport in all the models employed. H(2)S had no effect on Na(+) channels, whereas it decreased Na(+) /K(+)-ATPase currents. H(2)S did not affect the membrane abundance of Na(+) /K(+)-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H(2)S inhibited basolateral calcium-dependent K(+) channels, which consequently decreased Na(+) absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H(2) S impairs pulmonary transepithelial Na(+) absorption, mainly by inhibiting basolateral Ca(2+)-dependent K(+) channels. These data suggest that the H(2)S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na(+) transport.
The vectorial transport of Na+ across epithelia is crucial for the maintenance of Na+ and water homeostasis in organs such as the kidneys, lung, or intestine. Dysregulated Na+ transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, or intestinal disorders, which indicate that a precise regulation of epithelial Na+ transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence which indicates that gasotransmitters may also regulate Na+ transport across epithelia. This review will summarize the available data concerning NO, CO, and H2S dependent regulation of epithelial Na+ transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na+ transport biology.
More than 25 years ago, it was a big surprise for physiologists that nitric oxide (NO) was identified as the endothelium derived relaxing factor which is responsible for endothelium-induced smooth muscle relaxation (Ignarro et al., 1987). Until then, small gaseous molecules were simply regarded as byproducts of cellular metabolism which were unlikely to be of any physiological relevance. The discovery that NO was synthesized by specific enzymes (NO-synthases), upon stimulation by specific, physiologically relevant stimuli (e.g., acetylcholine stimulation of endothelial cells), as well as the fact that it acted on specific cellular targets (e.g., soluble guanylate cyclase), set the course for numerous studies which investigated the physiological roles of gaseous signaling molecules—in other words, gasotransmitters (Wang, 2002).
The development of pulmonary edema can be considered as a combination of alveolar flooding via increased fluid filtration, impaired alveolar-capillary barrier integrity, and disturbed resolution due to decreased alveolar fluid clearance. An important mechanism regulating alveolar fluid clearance is sodium transport across the alveolar epithelium. Transepithelial sodium transport is largely dependent on the activity of sodium channels in alveolar epithelial cells. This paper describes how sodium channels contribute to alveolar fluid clearance under physiological conditions and how deregulation of sodium channel activity might contribute to the pathogenesis of lung diseases associated with pulmonary edema. Furthermore, sodium channels as putative molecular targets for the treatment of pulmonary edema are discussed.
Carbon Monoxide Rapidly Impairs Alveolar Fluid Clearance by Inhibiting Epithelial Sodium Channels
(2009)
RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.
IT-Governance, Prüfung & Revision mal agil gedacht! Herausforderungen und Notwendigkeit eines Perspektivwechsels für IT-Governance, Prüfung & Revision viele Fallbeispiele zeigen die praktische Umsetzbarkeit auf Agilität und der Einsatz agiler Methoden sind heute nicht mehr nur auf IT-Projekte begrenzt, sondern prägen zunehmend ganze Organisationen. Dieses Buch zeigt auf, wie sich IT-Governance, Prüfung & Revision erfolgreich dem durch Agilität ausgelösten Wandel stellen können und wie sich der Umgang mit den Kernthemen Risiko & Unsicherheit verändert. Zum einen werden Ansätze für eine agile IT-Governance und eine agile Prüfung & Revision beschrieben, indem sie sich agile Werte und Vorgehensweisen zu eigen machen. Zum anderen werden IT-Governance, Prüfung & Revision befähigt, agile Projekte angemessen steuern und wirksam prüfen zu können.
The invention relates to compounds that include peptide and peptidomimetics that inhibit estrogen receptor dependent cell proliferation. The compounds of the invention are useful for treating cell proliferative disorders or physiological conditions characterized by undesirable or unwanted estrogen induced cell proliferation, including breast cancer.
This study presents the findings of a quantitative study on the use of Open Educational Resources (OER) and Open Educational Practices (OEP) in Higher Education and Adult Learning Institutions. The study is based on the results of an online survey targeted at four educational roles: educational policy makers; institutional policy makers/managers; educational professionals; and learners. The report encompasses five chapters and four annexes. Chapter I presents the survey and Chapter II discloses the main research questions and models. Chapter III characterises the universe of respondents. Chapter IV advances with a detailed survey analysis including an overview of key statistical data. Finally, Chapter V provides an exploratory in-depth analysis of some key issues: representations, attitudes and uses of OEP. The table of contents and the complete list of diagrams and tables can be found at the end of the report.
Over the years, entrepreneurship has proven to be one of the key roles towards development. The cycle of business start-ups and growth are linked to the socio-economic benefits of the global world at large. With a growing world population of over 7billion people, the existence of universities (both public &private) as well as enterprises has increased globally in the 21st century. The mission and purpose behind Universities, Entrepreneurship and Enterprises thrive on development in the areas of capacity building, skill acquisition, training and knowledge amongst others. Africa alone has a population of over 1.2billion people with about 650 recognized universities and over 140,000 registered businesses (enterprises) in Ghana alone. A case study in Ghana reveals three key drivers towards entrepreneurship and the role university education has played in various business establishments. The drivers are problem statements, resources and research findings. Some of these notions to business include the management of risk, research findings and customer relationship. These are major features that need critical attention and play a role in business and entrepreneurship in Africa. A major success in business and entrepreneurship is the utilization of the human resource population and the lifeline support given to households in terms of income, while a barrier being the limited access to credit support from the financial companies at the inception stages. In conclusion, this conference should develop a practical book guide on business start-ups and entrepreneurship knowledge to be used at the various universities in Africa to enhance development.
The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions.
This study sought to examine the relationship between the components of SMEs social capital and firm performance. Using the social capital theory and the resource-based view as the theoretical foundations and census, 1,532 SMEs were selected in the Accra Metropolis for the study. Empirical results from 717 SMEs, utilising the hierarchical linear regression model, revealed that owner/manger’s network relationships are beneficial to the firm depending on when the relationships are closed or opened. Moreover, the study found that social capital has a significant impact on the sales and market performance of small and medium-sized enterprises. The results also brought to the fore the fact that most social networks of SME entrepreneurs are family, friends and relatives, which most times can only be used for expressive purposes and not for instrumental gain. The practical implications of the results are also discussed.