Self tolerance in a minimal model of the idiotypic network

We consider the problem of self tolerance in the frame of a minimalistic model of the idiotypic network. A node of this network represents a population of B lymphocytes of the same idiotype which is encoded by a bit string. The links of the network connect nodes with (nearly) complementary strings. The population of a node survives if the number of occupied neighbours is not too small and not too large. There is an influx of lymphocytes with random idiotype from the bone marrow. Previous investigations have shown that this system evolves toward highly organized architectures, where the nodes can be classified into groups according to their statistical properties. The building principles of these architectures can be analytically described and the statistical results of simulations agree very well with results of a modular mean field theory. In this paper we present simulation results for the case that one or several nodes, playing the role of self, are permanently occupied. We observe that the group structure of the architecture is very similar to the case without self antigen, but organized such that the neighbours of the self are only weakly occupied, thus providing self tolerance. We also treat this situation in mean field theory which give results in good agreement with data from simulation.Comment: 7 pages, 6 figures, 1 tabl

Using cross-lingual information to cope with underspecification in formal ontologies

Description logics and other formal devices are frequently used as means for preventing or detecting mistakes in ontologies. Some of these devices are also capable of inferring the existence of inter-concept relationships that have not been explicitly entered into an ontology. A prerequisite, however, is that this information can be derived from those formal definitions of concepts and relationships which are included within the ontology. In this paper, we present a novel algorithm that is able to suggest relationships among existing concepts in a formal ontology that are not derivable from such formal definitions. The algorithm exploits cross-lingual information that is implicitly present in the collection of terms used in various languages to denote the concepts and relationships at issue. By using a specific experimental design, we are able to quantify the impact of cross-lingual information in coping with underspecification in formal ontologies

Internationalisation and Country Image "Being German" in Western Australia

Internationalisation strategies are influenced by the value and strategic importance of a global image and presence. A strong country image, like 'being German', contributes significantly to a product image. This paper considers the characteristics of the German national identity and the position of German business in the international environment. In addition, the paper considers the value of 'being German' and the link between German business and Australia, more specifically Western Australia. The paper reflects on data collected from German associated businesses in Western Australia by describing demographics and considering the active pursuit of, and reasons for, the German association

Entlastung des Arbeitsmarktes durch Umweltschutz?

"Umweltschutzmaßnahmen führen nicht nur dazu, daß der Volkswirtschaft Gesundheits-, Material- und Vegetationsschäden in Milliardenhöhe erspart bleiben. Umweltschutzmaßnahmen sorgen auch dafür, daß der Arbeitsmarkt entlastet wird. In diesem Aufsatz wird gezeigt, daß der "job-killer-Umweltschutz"-These (Arbeitsplatzverluste durch Kostenerhöhung in Grenzbetrieben, Konkurrenznachteile auf den Auslandsmärkten, Standortverlagerungen in das Ausland und Investitionsstaus) nur eine begrenzte Bedeutung zukommt. Denn den wenigen Tausend umweltschutzbedingten Arbeitsplatzverlusten steht eine wesentlich größere Zahl an Umweltschutzarbeitsplätzen im Bereich der Industrie und der öffentlichen Hand gegenüber; vorsichtig gerechnet 440.000. Mit einem Bündel weiterer beschäftigungswirksamer Maßnahmen, wie der Aktivierung des Eigeninteresses aller für den Umweltschutz, gezielter Umweltschutzsubventionen bei Unternehmen, höherer Umweltschutzinvestitionen von Bund und Ländern sowie verstärkter Arbeitsbeschaffungsmaßnahmen auf dem Umweltsektor, könnten etwa 250.000 bis 300.000 zusätzliche Umweltschutzarbeitsplätze geschaffen werden. Insgesamt würden sich die Umweltschutzarbeitsplätze dann auf rund 700.000 bis 750.000 belaufen." (Autorenreferat)Umweltschutz - Auswirkungen, Beschäftigungseffekte, Arbeitsmarkt

TFE and Spt4/5 open and close the RNA polymerase clamp during the transcription cycle

Transcription is an intrinsically dynamic process and requires the coordinated interplay of RNA polymerases (RNAPs) with nucleic acids and transcription factors. Classical structural biology techniques have revealed detailed snapshots of a subset of conformational states of the RNAP as they exist in crystals. A detailed view of the conformational space sampled by the RNAP and the molecular mechanisms of the basal transcription factors E (TFE) and Spt4/5 through conformational constraints has remained elusive. We monitored the conformational changes of the flexible clamp of the RNAP by combining a fluorescently labeled recombinant 12-subunit RNAP system with single-molecule FRET measurements. We measured and compared the distances across the DNA binding channel of the archaeal RNAP. Our results show that the transition of the closed to the open initiation complex, which occurs concomitant with DNA melting, is coordinated with an opening of the RNAP clamp that is stimulated by TFE. We show that the clamp in elongation complexes is modulated by the nontemplate strand and by the processivity factor Spt4/5, both of which stimulate transcription processivity. Taken together, our results reveal an intricate network of interactions within transcription complexes between RNAP, transcription factors, and nucleic acids that allosterically modulate the RNAP during the transcription cycle

Transport in the random Kronig-Penney model

The Kronig-Penney model with random Dirac potentials on the lattice \ZM has critical energies at which the Lyapunov exponent vanishes and the density of states has a van Hove singularity. This leads to a non-trivial quantum diffusion even though the spectrum is known to be pure-point

The G215R Mutation in the Cl−/H+-Antiporter ClC-7 Found in ADO II Osteopetrosis Does Not Abolish Function but Causes a Severe Trafficking Defect

Background: ClC-7 is a ubiquitous transporter which is broadly expressed in mammalian tissues. It is implied in the pathogenesis of lysosomal storage disease and osteopetrosis. Because of its endosomal/lysosomal localization it is still poorly characterized. Methodology/Principal Findings: An electrophysiological characterization of rat ClC-7 using solid-supported membrane-based electrophysiology is presented. The measured currents show the characteristics of ClC-7 and confirm its function as a Cl−/H+-antiporter. We have used rat ClC-7 in CHO cells as a model system to investigate the functionality and cellular localization of the wt transporter and its variant G213R ClC-7 which is the analogue of human G215R ClC-7 responsible for autosomal dominant osteopetrosis type II. Our study shows that rat G213R ClC-7 is functional but has a localization defect in CHO cells which prevents it from being correctly targeted to the lysosomal membrane. The electrophysiological assay is tested as a tool for drug discovery. The assay is validated with a number of drug candidates. It is shown that ClC-7 is inhibited by DIDS, NPPB and NS5818 at micromolar concentrations. Conclusions/Significance: It is suggested that the scenario found in the CHO model system also applies to the human transporter and that mislocalization rather than impaired functionality of G215R ClC-7 is the primary cause of the related autosomal dominant osteopetrosis type II. Furthermore, the robust solid-supported membrane-based electrophysiological assay is proposed for rapid screening for potential ClC-7 inhibitors which are discussed for treatment of osteoporosis