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Nitric oxide (NO) is an important regulator of Na+ reabsorption by pulmonary epithelial cells and therefore of alveolar fluid clearance. The mechanisms by which NO affects epithelial ion transport are poorly understood and vary from model to model. In this study, the effects of NO on sodium reabsorption by H441 cell monolayers were studied in an Ussing chamber. Two NO donors, (Z)-1-[N-(3-aminopropyl)-N-(n-propyl) amino]diazen-1-ium-1,2-diolate and diethylammonium(Z)-1-(N, N-diethylamino) diazen-1-ium-1,2-diolate, rapidly, reversibly, and dose-dependently reduced amiloride-sensitive, short-circuit currents across H441 cell monolayers. This effect was neutralized by the NO scavenger hemoglobin and was not observed with inactive NO donors. The effects of NO were not blocked by 8-bromoguanosine-3',5'-cyclic monophosphate or by soluble guanylate cyclase inhibitors (methylene blue and 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) and were therefore independent of soluble guanylate cyclase signaling. NO targeted apical, highly selective, amiloride-sensitive Na+ channels in basolaterally permeabilized H441 cell monolayers. NO had no effect on the activity of the human epithelial sodium channel heterologously expressed in Xenopus oocytes. NO decreased Na+/K+-ATPase activity in apically permeabilized H441 cell monolayers. The inhibition of Na+/K+-ATPase activity by NO was reversed by mercury and was mimicked by N-ethylmaleimide, which are agents that reverse and mimic, respectively, the reaction of NO with thiol groups. Consistent with these data, S-NO groups were detected on the Na+/K+-ATPase a subunit in response to NO-donor application, using a biotin-switch approach coupled to a Western blot. These data demonstrate that, in the H441 cell model, NO impairs Na+ reabsorption by interfering with the activity of highly selective Na+ channels and the Na+/K+-ATPase.
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.
Routing Attacks are a serious threat to communication in tactical MANETs. TOGBAD is a centralised approach, using topology graphs to detect such attacks. In this paper, we present TOGBAD's newly added wormhole detection capability. It is an adaptation of a wormhole detection method developed by Hu et al. This method is based on nodes' positions. We adapted it to the specific properties of tactical environments. Furthermore, we present simulation results which show TOGBAD's performance regarding the detection of wormhole attacks.
NMR structures of thiostrepton derivatives for characterization of the ribosomal binding site
(2011)
In an explorative study, we investigated on German schoolteachers how they use, reuse, produce and manage Open Educational Resources. The main questions in this research have been, what their motivators and barriers are in their use of Open Educational Resources, what others can learn from their Open Educational Practices, and what we can do to raise the dissemination level of OER in schools.
Adaptability as a Special Demand on Open Educational Resources: The Cultural Context of e-Learning
(2011)
Producing and providing Open Educational Resources (OERs) is driven by the concepts of openness and sharing. Although there already are a lot of free high-quality resources available, practitioners often rather rewrite learning resources than creatively embed (and thus, reuse) existing OERs. In this paper, we analyse the reasons for this in two different educational contexts. As a result of this analysis, we found that the uncertainty on possible adaptation needs is one of the major barriers. In order to overcome this barrier and make different learning contexts comparable, we analysed the context of learners and in particular, in the research project ‘Learning Culture’, we investigated the field of culturally motivated expectations and attitudes of learners. This paper shows the results of this research project and discusses which cultural issues should be taken into consideration when OERs are to be adapted from one to another cultural context.
Selective screening for inborn errors of metabolism--assessment of metabolites in body fluids
(2011)
Die Zukunft der CCS-Technologie ist maßgeblich von den Entwicklungsmöglichkeiten abhängig, die ihr der Gesetzgeber einräumt. Der von der Bundesregierung am 13.4.2011 beschlossene Gesetzentwurf geht mit großer Vorsicht an den Einsatz der CCS-Technologie heran. Die Entwicklung sowie die Planungs- und Investitionssicherheit haben gegenüber den Bedenken gegen die kurz- und langfristige Sicherheit der CO2-Speicherung zurückstecken müssen. Der nachfolgende Beitrag erläutert Rechtsprobleme der Genehmigung von CO2-Abscheidungsanlagen, Transportleitungen und Speichern sowie der Gefahrenvorsorge, -nachsorge und Haftung.
At present, data publication is one of the most dynamic topics in e-Research. While the fundamental problems of electronic text publication have been solved in the past decade, standards for the external and internal organisation of data repositories are advanced in some research disciplines but underdeveloped in others. We discuss the differences between an electronic text publication and a data publication and the challenges that result from these differences for the data publication process. We place the data publication process in the context of the human knowledge spiral and discuss key factors for the successful acquisition of research data from the point of view of a data repository. For the relevant activities of the publication process, we list some of the measures and best practices of successful data repositories.
Liquid–liquid equilibria of dipropylene glycol dimethyl ether and water by molecular dynamics
(2011)
While industrialized countries are becoming service economies, all countries are becoming global. As competition becomes more global, understanding and accommodating the needs of international customers with different cultural backgrounds has become increasingly important. This study highlights cross-cultural perceptions of service problems in the tourist industry.
Projektmanagement im Mittelstand? Häufig Fehlanzeige, seufzen Beobachter. Mit modernen Methoden der Projektabwicklung, wie sie sich seit vielen Jahren etwa in Konzernen bewährt haben, wollen mittelständische Unternehmen wenig zu tun haben. Doch Vorsicht! Professor Uwe Braehmer warnt vor Pauschalurteilen. Einige Mittelständler beherrschen meisterhaft die Klaviatur des Projektmanagements. Andere erkennen derzeit neue Geschäftschancen durch Projektmanagement. Und wieder andere brauchen ein dem Mittelstand speziell angepasstes Projektmanagement. Professor Uwe Braehmer weiß: „Auf viele mittelständische Geschäftsführer wirkt Projektmanagement zu akademisch und zu groß dimensioniert.“ Bedarfsgerecht gestaltet könne es im Mittelstand eine wesentlich breitere Akzeptanz finden.
Streptococcus agalactiae is the leading cause of bacterial sepsis and meningitis in neonates and is also the causative agent of several serious infections in immunocompromised adults. S. agalactiae encounters multiple niches during an infection, suggesting that regulatory mechanisms control the expression of specific virulence factors in this bacterium. The present study describes the functional characterization of a gene from S. agalactiae, designated rga, which encodes a protein with significant similarity to members of the RofA-like protein (RALP) family of transcriptional regulators. After deletion of the rga gene in the genome of S. agalactiae, the mutant strain exhibited significantly reduced expression of the genes srr-1 and pilA, which encode a serine-rich repeat surface glycoprotein and a pilus protein, respectively, and moderately increased expression of the fbsA gene, which encodes a fibrinogen-binding protein. Electrophoretic mobility shift assays demonstrated specific DNA binding of purified Rga to the promoter regions of pilA and fbsA, suggesting that Rga directly controls pilA and fbsA. Adherence assays revealed significantly reduced binding of the Δrga mutant to epithelial HEp-2 cells and to immobilized human keratin 4, respectively. In contrast, the adherence of the Δrga mutant to A549 cells and its binding to human fibrinogen was significantly increased. Immunoblot and immunoelectron microscopy revealed that the quantity of pilus structures was significantly reduced in the Δrga mutant compared with the parental strain. The wild-type phenotype could be restored by plasmid-mediated expression of rga, demonstrating that the mutant phenotypes resulted from a loss of Rga function.
Balanites aegyptiaca (Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract from B. aegyptiaca seeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC(50) value for the chloroquine-susceptible Plasmodium falciparum NF54 strain was 68.26 μg/μL ± 3.5. Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for the in vitro antiplasmodial activity. The crude plant extract had a K(i) of 2.35 μg/μL and showed a dose-dependent response. After depletion of the compound, a significantly lower inhibition was determined with a K(i) of 4.8 μg/μL. Moreover, two phenolic compounds, that is, 2,6-di-tert-butyl-phenol and 2,4-di-tert-butyl-phenol, with determined IC(50) values of 50.29 μM ± 3 and 47.82 μM ± 2.5, respectively, were detected. These compounds may contribute to the in vitro antimalarial activity due to their antioxidative properties. In an in vivo experiment, treatment of BALB/c mice with the aqueous Balanite extract did not lead to eradication of the parasites, although a reduced parasitemia at day 12 p.i. was observed.
JNK1, but Not JNK2, Is Required in Two Mechanistically Distinct Models of Inflammatory Arthritis
(2011)
In this paper, the performance evaluation of Frequency Modulated Chaotic On-Off Keying (FM-COOK) in AWGN, Rayleigh and Rician fading channels is given. The simulation results show that an improvement in BER can be gained by incorporating the FM modulation with COOK for SNR values less than 10dB in AWGN case and less than 6dB for Rayleigh and Rician fading channels.