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Wesch D, Miranda P, Afonso-Oramas D, Althaus M, Castro-Hernandez J, Dominguez J, Morty RE, Clauss W, Gonzalez-Hernandez T, Alvarez de la Rosa D, Giraldez T. The neuronalspecific SGK1.1 kinase regulates delta-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling. Am J Physiol Cell Physiol 299: C779-C790, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00184.2010.-The delta-subunit of the epithelial Na+ channel (ENaC) is expressed in neurons of the human and monkey central nervous system and forms voltage-independent, amiloride-sensitive Na+ channels when expressed in heterologous systems. It has been proposed that delta-ENaC could affect neuronal excitability and participate in the transduction of ischemic signals during hypoxia or inflammation. The regulation of delta-ENaC activity is poorly understood. ENaC channels in kidney epithelial cells are regulated by the serum-and glucocorticoid-induced kinase 1 (SGK1). Recently, a new isoform of this kinase (SGK1.1) has been described in the central nervous system. Here we show that delta-ENaC isoforms and SGK1.1 are coexpressed in pyramidal neurons of the human and monkey (Macaca fascicularis) cerebral cortex. Coexpression of delta beta gamma-ENaC and SGK1.1 in Xenopus oocytes increases amiloride-sensitive current and channel plasma membrane abundance. The kinase also exerts its effect when delta-subunits are expressed alone, indicating that the process is not dependent on accessory subunits or the presence of PY motifs in the channel. Furthermore, SGK1.1 action depends on its enzymatic activity and binding to phosphatidylinositol(4,5)-bisphosphate. Physiological or pharmacological activation of phospholipase C abrogates SGK1.1 interaction with the plasma membrane and modulation of delta-ENaC. Our data support a physiological role for SGK1.1 in the regulation of delta-ENaC through a pathway that differs from the classical one and suggest that the kinase could serve as an integrator of different signaling pathways converging on the channel.
Die Debatte um muslimische Einwandernde in Deutschland, die in jüngster Zeit neuen Auftrieb erhalten hat (1), offenbart immer wieder simplifizierende Sichtweisen vom Islam als einer homogenen Religion. Dabei beweist bereits ein Blick auf die vielfältige muslimische Organisationslandschaft in Deutschland: Es gibt nicht den Islam, sondern stattdessen eine Vielzahl unterschiedlicher islamischer Strömungen, welche mitunter in Konkurrenz zu einander stehen und sich mal mehr, mal weniger deutlich voneinander abgrenzen. Diese Vielfalt der MuslimInnen in Deutschland sowie ihr eher geringer Organisationsgrad erschwert die Bildung eines zentralen islamischen Ansprechpartners, der für sich in Anspruch nehmen könnte, für die Mehrheit der MuslimInnen in Deutschland zu sprechen.
Usable Security und Privacy
(2010)
When entering a password (or other secrets) the typed input is most commonly masked, i.e. the characters are hidden behind bullets or asterisks. This, however, complicates the input and highly decreases the user's confident causing several issues such as login failure attempts. On the other hand, password masking is an important security requirement for a lot of applications and contexts to prevent a third person to read the password. Thus, simply dropping password masking is not feasible in general. A common solution provides the user with the choice of toggling password masking on and off, but due to distinct defaults (in dependency of the application and context) this is rather complex and confusing. Enhanced password visualization technologies beyond the simple masking of passwords can provide more sophisticated solutions from both a usability and security perspective. In this paper, available password visualization technologies are presented and discussed. Furthermore a novel password visualization approach is introduced, the TransparentMask, which provides unique properties in comparison to the existing schemes. Amongst these are the ability to detect mistakes while typing and being able to localize and correct the typo within a certain range. Finally, a security analysis of the TransparentMask shows that the protection level given by a certain password length is slightly decreased in comparison to the fully masked approach.
In this paper, we present a solution how to test cultural influences on E-Learning in a global context. Based on a metadata approach, we show how specifically cultural influence factors can be determined to transfer and adapt learning environments. We present a method how those influence factors can be validated for both, to improve the dynamical meta-data specification and to be used in the development of (international) E-Learning scenarios.
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.
Eine internationale Verbreitung von OER ist u. a. davon abhängig, ob bereitstehende Inhalte an den jeweiligen Kontext angepasst werden können. Dieser Beitrag befasst sich mit studierendenspezifischen, kulturell motivierten Einflussfaktoren auf Lernsituationen, die neben u. a. inhaltlichen, technischen, didaktischen und rechtlichen Fragen für eine erfolgreiche Wiederverwendung von bereits etablierten Lernressourcen prüfend berücksichtigt werden sollten.
Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients
(2010)
Dihydropyrimidine Dehydrogenase Deficiency Caused by a Novel Genomic Deletion c.505_513del of DPYD
(2010)
Changes in plasma amino acid concentrations with increasing age in patients with propionic acidemia
(2010)
The aim of the study was to develop a method for fast and reliable diagnosis of peroxisomal diseases and to facilitate differential diagnosis of cholestatic hepatopathy. For the quantification of bile acids and their conjugates as well as C(27) precursors di- and trihydroxycholestanoic acid (DHCA, THCA), in small pediatric blood samples we combined HPLC separation on a reverse-phase C18 column with ESI-MS/MS analysis in the negative ion mode. Analysis was done with good precision (CV 3,7%-11.1%) and sufficient sensitivity (LOQ: 11-91 nmol/L) without derivatization. Complete analysis of 17 free and conjugated bile acids from dried blood spots and 10 microL serum samples, respectively, was performed within 12 min. Measurement of conjugated primary bile acids plus DHCA and THCA as well as ursodeoxycholic acid was done in 4.5 min. In blood spots of healthy newborns, conjugated primary bile acids were found in the range of 0.01 to 2.01 micromol/L. Concentrations of C(27) precursors were below the detection limit in normal controls. DHCA and THCA were specifically elevated in cases of peroxysomal defects and one Zellweger patient.
One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors.
BACKGROUND
Activator protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2alpha and AP-2gamma is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms.
METHODS
We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant.
RESULTS
We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network.
CONCLUSIONS
Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention.
Ende des Elends in Afrika?
(2010)
Nach 50 Jahren Entwicklungspolitik ist Subsahara-Afrika immer noch im Elend, auch wegen der Entwicklungshilfe. Diese hat oft mehr geschadet als genützt. Mit hunderttausenden Projekten und Milliarden von Hilfsgeldern ist es nicht gelungen, Afrika zu einer selbsttragenden wirtschaftlichen und sozialen Entwicklung zu verhelfen.
Die Dritte Welt in der fossilen Ressourcenfalle – Ressourcenabhängigkeit trotz Ressourcenreichtum
(2010)
Die Städte der Dritten Welt orientierten sich in der nachkolonialen Ära wie selbstverständlich am Vorbild der industriegesellschaftlichen Entwicklung und damit an deren energieintensivem Wachstumsmodell. Dadurch wurden und werden sie unvermittelt und ohne Zeit zur Anpassung einer Wachstumsflut ausgesetzt. Ein beispielloser Zuzug überschwemmt die Städte der Dritten Welt und überfordert in kürzester Zeit ihre Infrastruktur.
Weltentwicklungspolitik – Aufgabe kompetenter und demokratisch legitimierter Globaler Staatlichkeit
(2010)
Global change management: Eine systemische Utopie der Nachhaltigkeit im Angesicht der Apokalypse
(2010)
Für jeden Bürger wird es durch die Berichterstattung in den Medien täglich Realität, dass die globale Welt sich an einem entscheidenden Wendepunkt befindet. Immer mehr Entwicklungsländer werden zu wichtigen Mitspielern auf diesem Globus. Dies hat vielfältige Auswirkungen. So ist auch die traditionelle Entwicklungshilfe einer grundlegenden Prüfung zu unterziehen. Aus der liebgewordenen Nische einer nationalen Politik muss sie sich wandeln zu einem globalen Politikdialog, der mit genau abgestimmten Förderprogrammen verbunden ist. Nur so kann langfristig die Armut wirklich nachhaltig reduziert werden. Der Autor analysiert aber darüber hinaus auch, wie sich in den nächsten Jahrzehnten die wirtschaftlichen und politischen Gewichte zwischen den einzelnen Weltregionen und großen Nationen verschieben werden. Umwelt, Bevölkerungsentwicklung und soziale Lebensbedingungen sind hierbei entscheidende Faktoren. Über eine intensivere regionale Kooperation stellt sich dann aber auch die Frage nach einer stärkeren Rolle der Vereinten Nationen bzw. einer zukünftigen Weltregierung.
Glücksspielrecht im Umbruch
(2010)
Environment monitoring using multiple observation cameras is increasingly popular. Different techniques exist to visualize the incoming video streams, but only few evaluations are available to find the best suitable one for a given task and context. This article compares three techniques for browsing video feeds from cameras that are located around the user in an unstructured manner. The techniques allow mobile users to gain extra information about the surroundings, the objects and the actors in the environment by observing a site from different perspectives. The techniques relate local and remote cameras topologically, via a tunnel, or via bird's eye viewpoint. Their common goal is to enhance spatial awareness of the viewer, without relying on a model or previous knowledge of the environment. We introduce several factors of spatial awareness inherent to multi-camera systems, and present a comparative evaluation of the proposed techniques with respect to spatial understanding and workload.
In this paper, we report on four generations of display-sensor platforms for handheld augmented reality. The paper is organized as a compendium of requirements that guided the design and construction of each generation of the handheld platforms. The first generation, reported in [17]), was a result of various studies on ergonomics and human factors. Thereafter, each following iteration in the design-production process was guided by experiences and evaluations that resulted in new guidelines for future versions. We describe the evolution of hardware for handheld augmented reality, the requirements and guidelines that motivated its construction.
Ab April 2011 erhält die Hochschule Bonn-Rhein-Sieg günstiges Gas von LogoEnergie. Das ist das Ergebnis einer europaweit durchgeführten Ausschreibung, die der Berliner Energie-Broker Ampere AG im Auftrag der öffentlichen Einrichtung durchführte. Durch den Versorgerwechsel erzielt die Hochschule in den kommenden zwei Jahren trotz der schwierigen Marktsituation deutliche Einsparungen bei ihren Energiekosten.
Heterodyne gas cell measurements at 2.9 THz using a quantum cascade laser as local oscillator
(2010)
The Fraunhofer Institute for Algorithms and Scientific Computing (SCAI) has developed a software tool for the automated parameterization of force fields for molecular simulations using efficient gradient-based algorithms. This tool, combined with well-established simulation techniques, can quantitatively determine many physicochemical properties for given compounds.
GROW: A gradient-based optimization workflow for the automated development of molecular models
(2010)
Exemplarische Untersuchungen zum Potenzial von LTE zur Breitbandversorgung ländlicher Regionen
(2010)
Anhand von Funkfeldmessungen in mehreren ausgewählten Orten im Hochsauerlandkreis wird die Frage diskutiert, welchen Beitrag der Aufbau eines LTE-Netzes zur Breitbandversorgung von bisher unterversorgten Gebieten im ländlichen Raum liefern kann - und dies unter Verwendung bestehender GSM-Basisstationsstandorte und dem Frequenzbereich der Digitalen Dividende. Für verschiedene Szenarien werden Empfangspegelstatistiken mit geforderten Empfängerempfindlichkeiten verglichen, Statistiken zur zu erwartenden Datenraten abgeleitet und Netzkapazitäten abgeschätzt. Dabei zeigt sich, dass i. A. sowohl der Empfangspegel als auch die Netzkapazität ausreichen, um mittels LTE eine genügende Zahl von Anschlüssen mit einer Downlink-Datenrate von mindestens 1 Mbit/s in den untersuchten Ortschaften bereit zu stellen. Hohe Versorgungsgrade mit Datenraten von 50 Mbit/s sind jedoch nicht zu erwarten. Durch eine Außeninstallation der Endgeräteantennen lassen sich auch bei 2600 MHz nahezu optimale Empfangsbedingungen erzielen. Insofern scheint ein Mischbetrieb mit Frequenzen im 800- und im 2600-MHz-Bereich geeignet, die Netzkapazität auch im ländlichen Raum zu erhöhen.
Kultur, Recht und Minderheiten: Rechtsphilosophische Überlegungen zur Typologie von Minderheiten
(2010)
Dawning of a new global order – An essay on global transformations from an European perspective
(2010)
Action planning has been used in the field of robotics for solving long-running tasks. In the robot architectures field, it is also known as the deliberative layer. However, there is still a gap between the symbolic representation on the one hand and the low-level control and sensor representation on the other. In addition, the definition of a planning problem for a complex, real-world robot is not trivial. The planning process could become intractable as its search spaces become large.
Automated force field optimisation of small molecules using a gradient-based workflow package
(2010)
In this study, the recently developed gradient-based optimisation workflow for the automated development of molecular models is for the first time applied to the parameterisation of force fields for molecular dynamics simulations. As a proof-of-concept, two small molecules (benzene and phosgene) are considered. In order to optimise the underlying intermolecular force field (described by the (12,6)-Lennard-Jones and the Coulomb potential), the energetic and diameter parameters ε and σ are fitted to experimental physical properties by gradient-based numerical optimisation techniques. Thereby, a quadratic loss function between experimental and simulated target properties is minimised with respect to the force field parameters. In this proof-of-concept, the considered physical target properties are chosen to be diverse: density, enthalpy of vapourisation and self-diffusion coefficient are optimised simultaneously at different temperatures. We found that in both cases, the optimisation could be successfully concluded by fulfillment of a pre-defined stopping criterion. Since a fairly small number of iterations were needed to do so, this study will serve as a good starting point for more complex systems and further improvements of the parametrisation task.