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Weltentwicklungspolitik – Aufgabe kompetenter und demokratisch legitimierter Globaler Staatlichkeit
(2010)
The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species
(1994)
RNA is one of the most important molecules in living organisms. One of its main functions is to regulate gene expression. This involves binding to and forming a joint structure with a messenger RNA. An RNAs functions is determined by its sequence and the structure it folds into. Accordingly, the prediction of individual as well as joint structures is an important area of research. In this thesis a method for the prediction of RNA-RNA joint structure using their minimum free energy (mfe) structures was developed. It is able to extensively explore the joint structural landscape of two interacting RNAs by taking advantage of the locality of changes in the RNAs structures as well as natural and energetic constraints. The method predicts the mfe joint structure as well as alternative stable joint structures while also computing non-optimal folding pathways from the unbound individual mfe structures to the predicted joint structures. It is shown how an enumeration approach is used which is able to deal with the enormous search space as well as to avoid any cyclic behaviour. The method is evaluated using two standard datasets of known interacting RNAs and shows good results.
MOTIVATION: The genome projects produce a wealth of protein sequences. Theoretical methods to predict possible structures and functions are needed for screening purposes, large-scale comparisons and in-depth analysis to identify worthwhile targets for further experimental research. Sequence-structure alignment is a basic tool for the identification of model folds for protein sequences and the construction of crude structural models. Empirical contact potentials (potentials of mean force) are used to optimize and evaluate such alignments. RESULTS: We propose new scoring schemes based on a contact definition derived from Voronoi decompositions of the three-dimensional coordinates of protein structures. We demonstrate that Voronoi potentials are superior to pure distance-based contact potentials with respect to recognition rate and significance for native folds. Moreover, the scoring scheme has the potential to provide a reasonable balance of detail and ion such that it is also useful for the recognition of distantly related (both homologous and non-homologous) proteins. This is demonstrated here on a set of structural alignments showing much better correspondence of native and model scores for the Voronoi potentials as compared to conventional distance-based potentials.
Scientific or statistical research has long been the domain of dedicated programming languages such as R, SPSS or SAS. A few years other competitors entered the arena, among them Python with its powerful SciPy package. The following article introduces SciPy by applying a small subset of its functionality to a well-known dataset.
Nützt oder schadet ethisches Verhalten der Karriere und dem Erfolg der Mitarbeiter und ihrer Unternehmen? Wenn man gerade die letzten 10 Entwicklungsjahre in vielen Unternehmen sieht, könnte man spontan die Meinung vertreten, dass Ethik und Moral der Karriere eher schadet, legt man den Maßstab an moralische Qualitäten des täglichen Handelns.
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1 beta (IL-1 beta) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of alpha 7, alpha 9 and/or alpha 10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits alpha 9 and alpha 10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1 beta by acetylcholine (ACh), nicotine and PC depends on subunits alpha 7, alpha 9 and alpha 10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1 beta release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1 beta. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits alpha 9 and alpha 10, but only to a small degree on alpha 7. In Xenopus laevis oocytes heterologously expressing different combinations of human alpha 7, alpha 9 or alpha 10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits alpha 7, alpha 9 and alpha 10. For the metabotropic signaling of LPC and G-PC, nAChR subunits alpha 9 and alpha 10 are needed, whereas alpha 7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to regulate immune functions without perturbing canonical ion channel functions of nAChR.
A framework of decision‐support systems in advanced manufacturing enterprises ‐ a systems view
(1997)
Helping Johnny to Analyze Malware: A Usability-Optimized Decompiler and Malware Analysis User Study
(2016)
The dawn of the 21st Century has witnessed a tremendous increase in trade pacts among nations, resulting in renewed hopes for sustainable enterprise development in emerging economies worldwide. Ghana and other sub- Saharan African (SSA) countries have signed onto several North-South and South-South free trade agreements with the hope of strengthening their presence in the international trade arena, and to promote economic growth in SSA. For over two decades, however, very little has changed, and many have dashed their high hopes as enterprises continue to struggle in SSA. Not even the African Continental Free Trade Agreement (AfCFTA) could renew the hopes of sceptics. Several studies opined that enterprises in SSA could improve their domestic and international competitiveness by establishing mutually beneficial partnerships with their counterparts from the Global North and South. This study delved into the issues that affect North-South and South-South business collaborations and recommends key success factors that could help promote mutually beneficial cross-border business partnerships. The research includes both literature and empirical information on the key success factors of business partnerships between African enterprises as well as between African enterprises and firms from the Global North. We approached the study qualitatively using a phenomenological research design. Research participants included important stakeholders in Africa and Europe's international trade and sustainable enterprise development ecosystem. The study identified several challenges with the current business collaborations and recommended new ways of making such partnerships more beneficial.
Am Beispiel der Scientology-Bewegung wird der Frage nachgegangen, ueber welche kommunikativen Beeinflussungsstrategien Sekten Mitglieder anwerben und an sich binden. Nach einleitenden Anmerkungen zur aktuellen Bedeutung von Sekten und destruktiven Kulten in der Gesellschaft werden Entstehung, Gedankengebaeude und Organisationsstruktur der Scientology-Bewegung skizziert. Anschliessend werden deren kommunikative Beeinflussungstechniken beschrieben, wobei zwischen oeffentlichkeitsbezogenen Sozialtechniken zur Image-Pflege und Mitgliedergewinnung und sekteninternen Sozialtechniken zur "psychischen Umpolung" und zur Sozialisation und Bindung der Mitglieder differenziert wird. Des weiteren werden praeventive und intervenierende Massnahmen zum Schutz gegenueber kommunikativer Beeinflussung durch Sekten behandelt.
Die erlebnisbetonte Positionierung von Produkten und Dienstleistungen ist heute weit verbreitet. Wer in der Flut emotionaler Werbebilder auffallen will, muß strategisch vorgehen und benötigt zunächst einen Überblick über die aktuelle Werbelandschaft. Eine objektive Analyse des Bedeutungsgehalts bildbetonter emotionaler Werbung ist aber schwierig, da diese Werbung in der Regel spontan wirkt und beim Betrachter vielfältige Assoziationen auslöst.
Multimediaprojectors require sophisticated image processing realized on limited board space. An architecture is presented that combines available components and a dedicated display controller for a flexible, compact and cost efficient display electronic. A basic version of the display controller is available as an ASIC, an advanced version has been prototyped as an FPGA.
Images displayed by projection systems can experience geometric distortions. These distortions can be compensated for by electronic correction, also called image warping. When the image that will be displayed is composed of several input sources, the different image layers have to be corrected independently from each other in order to achieve optimal image quality. A VLSI architecture for independent electronic correction of multiple image layers is proposed.
Optical distortions, resulting from lens characteristics, non-aligned projection and variations in the light source, decrease the quality of projection displays. Knowledge of the sources and characteristics of these distortions allows their electronic correction. The integration of electronic image correction in the display controller IC allows high quality projection without additional components.
Reduktion der Verlustleistung integrierter CMOS-Schaltungen durch Anpassung an Signaleigenschaften
(1995)
Influence of Statistical Properties of Video Signals on the Power Dissipation of CMOS Circuits
(1994)
Reduktion des Schaltfaktors durch das Ausnutzen statistischer Eigenschaften von Videosignalen
(1994)
Mit dem Dual Shore Delivery Model Sprach- und Kulturbarrieren bei IT-Offshoreprojekten überwinden
(2005)
Millimetron is a Russian-led 12 m diameter submillimeter and far-infrared space observatory which is included in the Space Plan of the Russian Federation for launch around 2017. With its large collecting area and state-of-the-art receivers, it will enable unique science and allow at least one order of magnitude improvement with respect to the Herschel Space Observatory. Millimetron will be operated in two basic observing modes: as a single-dish observatory, and as an element of a ground-space very long baseline interferometry (VLBI) system. As single-dish, angular resolutions on the order of 3 to 12 arc sec will be achieved and spectral resolutions of up to a million employing heterodyne techniques. As VLBI antenna, the chosen elliptical orbit will provide extremely large VLBI baselines (beyond 300,000 km) resulting in micro-arc second angular resolution.
Cosynthesis in CASTLE
(1995)
Risk-based authentication (RBA) is an adaptive security measure to strengthen password-based authentication. RBA monitors additional implicit features during password entry such as device or geolocation information, and requests additional authentication factors if a certain risk level is detected. RBA is recommended by the NIST digital identity guidelines, is used by several large online services, and offers protection against security risks such as password database leaks, credential stuffing, insecure passwords and large-scale guessing attacks. Despite its relevance, the procedures used by RBA-instrumented online services are currently not disclosed. Consequently, there is little scientific research about RBA, slowing down progress and deeper understanding, making it harder for end users to understand the security provided by the services they use and trust, and hindering the widespread adoption of RBA.
In this paper, with a series of studies on eight popular online services, we (i) analyze which features and combinations/classifiers are used and are useful in practical instances, (ii) develop a framework and a methodology to measure RBA in the wild, and (iii) survey and discuss the differences in the user interface for RBA. Following this, our work provides a first deeper understanding of practical RBA deployments and helps fostering further research in this direction.
Risikobasierte Authentifizierung (RBA) ist eine adaptive Sicherheitsmaßnahme zur Stärkung passwortbasierter Authentifizierung. Sie zeichnet Merkmale während des Logins auf und fordert zusätzliche Authentifizierung an, wenn sich Ausprägungen dieser Merkmale signifikant von den bisher bekannten unterscheiden. RBA bietet das Potenzial für gebrauchstauglichere Sicherheit. Bisher jedoch wurde RBA noch nicht ausreichend im Bezug auf Usability, Sicherheit und Privatsphäre untersucht. Dieser Extended Abstract legt das geplante Dissertationsvorhaben zur Erforschung von RBA dar. Innerhalb des Vorhabens konnte bereits eine Grundlagenstudie und eine darauf aufbauende Laborstudie durchgeführt werden. Wir präsentieren erste Ergebnisse dieser Studien und geben einen Ausblick auf weitere Schritte.
The epithelial sodium channel (ENaC) is a critical regulator of vertebrate electrolyte homeostasis. ENaC is the only constitutively open ion channel in the degenerin/ENaC protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. The canonical ENaC is composed of three subunits (, , and ), but a fourth -subunit may replace and form atypical -ENaCs. Using Xenopus laevis as a model, here we found that mRNAs of the - and -subunits are differentially expressed in different tissues and that -ENaC predominantly is present in the urogenital tract. Using whole-cell and single-channel electrophysiology of oocytes expressing Xenopus - or -ENaC, we demonstrate that the presence of the -subunit enhances the amount of current generated by ENaC due to an increased open probability, but also changes current into a transient form. Activity of canonical ENaCs is critically dependent on proteolytic processing of the - and -subunits, and immunoblotting with epitope-tagged ENaC subunits indicated that, unlike -ENaC, the -subunit does not undergo proteolytic maturation by the endogenous protease furin. Furthermore, currents generated by -ENaC were insensitive to activation by extracellular chymotrypsin, and presence of the -subunit prevented cleavage of -ENaC at the cell surface. Our findings suggest that subunit composition constitutes an additional level of ENaC regulation, and we propose that the Xenopus -ENaC subunit represents a functional example that demonstrates the importance of proteolytic maturation during ENaC evolution.
The limited sodium availability of freshwater and terrestrial environments was a major physiological challenge during vertebrate evolution. The epithelial sodium channel (ENaC) is present in the apical membrane of sodium-absorbing vertebrate epithelia and evolved as part of a machinery for efficient sodium conservation. ENaC belongs to the degenerin/ENaC protein family and is the only member that opens without an external stimulus. We hypothesized that ENaC evolved from a proton-activated sodium channel present in ionocytes of freshwater vertebrates and therefore investigated whether such ancestral traits are present in ENaC isoforms of the aquatic pipid frog Xenopus laevis. Using whole-cell and single-channel electrophysiology of Xenopus oocytes expressing ENaC isoforms assembled from alpha beta gamma- or delta beta gamma-subunit combinations, we demonstrate that Xenopus delta beta gamma-ENaC is profoundly activated by extracellular acidification within biologically relevant ranges (pH 8.0-6.0). This effect was not observed in Xenopus alpha beta gamma-ENaC or human ENaC orthologs. We show that protons interfere with allosteric ENaC inhibition by extracellular sodium ions, thereby increasing the probability of channel opening. Using homology modeling of ENaC structure and site-directed mutagenesis, we identified a cleft region within the extracellular loop of the delta-subunit that contains several acidic amino acid residues that confer proton-sensitivity and enable allosteric inhibition by extracellular sodium ions. We propose that Xenopus delta beta gamma-ENaC can serve as a model for investigating ENaC transformation from a proton-activated toward a constitutively-active ion channel. Such transformation might have occurred during the evolution of tetrapod vertebrates to enable bulk sodium absorption during the water-to-land transition.
Der globalisierte Kapitalismus, Umweltkatastrophen, Überbevölkerung sowie zunehmende politisch und religiös motivierte Konflikte fordern ein Umdenken ökonomischer Konzepte. Allein mit den herkömmlichen Sozial- und Wirtschaftssystemen lassen sich existenzbedrohende Probleme wie Armut, Hunger, Krankheit, mangelnde Bildung und Betreuung nicht lösen. Es gilt dringend, neue, zukunftsweisende unternehmerische Konzepte zu entwickeln und zu fördern. Seit geraumer Zeit hat sich unter dem Begriff „Social Entrepreneurship“ eine Bewegung etabliert, die versucht, unter Beachtung klassischer Ökonomiegrundsätze gesellschaftliche Herausforderungen nachhaltig zu lösen.
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.
Wesch D, Althaus M, Miranda P, Cruz-Muros I, Fronius M, Gonzalez-Hernandez T, Clauss WG, de la Rosa DA, Giraldez T. Differential N termini in epithelial Na+ channel delta-subunit isoforms modulate channel trafficking to the membrane. Am J Physiol Cell Physiol 302: C868-C879, 2012. First published December 7, 2011; doi: 10.1152/ajpcell.00255.2011.-The epithelial Na+ channel (ENaC) is a heteromultimeric ion channel that plays a key role in Na+ reabsorption across tight epithelia. The canonical ENaC is formed by three analogous subunits, alpha, beta, and gamma. A fourth ENaC subunit, named delta, is expressed in the nervous system of primates, where its role is unknown. The human delta-ENaC gene generates at least two splice isoforms, delta(1) and delta(2), differing in the N-terminal sequence. Neurons in diverse areas of the human and monkey brain differentially express either delta(1) or delta(2), with few cells coexpressing both isoforms, which suggests that they may play specific physiological roles. Here we show that heterologous expression of delta(1) in Xenopus oocytes and HEK293 cells produces higher current levels than delta(2). Patch-clamp experiments showed no differences in single channel current magnitude and open probability between isoforms. Steady-state plasma membrane abundance accounts for the dissimilarity in macroscopic current levels. Differential trafficking between isoforms is independent of beta- and gamma-subunits, PY-motif-mediated endocytosis, or the presence of additional lysine residues in delta(2)-N terminus. Analysis of delta(2)-N terminus identified two sequences that independently reduce channel abundance in the plasma membrane. The delta(1) higher abundance is consistent with an increased insertion rate into the membrane, since endocytosis rates of both isoforms are indistinguishable. Finally, we conclude that delta-ENaC undergoes dynamin-independent endocytosis as opposed to alpha beta gamma-channels.
Mobilität und Bindungsformen von Cd, Cr, As und V in urbanen Böden unterschiedlicher Belastung
(1995)
Towards explaining deep learning networks to distinguish facial expressions of pain and emotions
(2018)
Deep learning networks are successfully used for object and face recognition in images and videos. In order to be able to apply such networks in practice, for example in hospitals as a pain recognition tool, the current procedures are only suitable to a limited extent. The advantage of deep learning methods is that they can learn complex non-linear relationships between raw data and target classes without limiting themselves to a set of hand-crafted features provided by humans. However, the disadvantage is that due to the complexity of these networks, it is not possible to interpret the knowledge that is stored inside the network. It is a black-box learning procedure. Explainable Artificial Intelligence (AI) approaches mitigate this problem by extracting explanations for decisions and representing them in a human-interpretable form. The aim of this paper is to investigate the explainable AI method Layer-wise Relevance Propagation (LRP) and apply it to explain how a deep learning network distinguishes facial expressions of pain from facial expressions of emotions such as happiness and disgust.
Two distinct sequence elements mediate retroviral gene expression in embryonal carcinoma cells
(1987)