Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse

Ligation of T cell receptor (TCR) to peptide-MHC (pMHC) complexes initiates signaling leading to T cell activation and TCR ubiquitination. Ubiquitinated TCR is then either internalized by the T cell or released toward the antigen-presenting cell (APC) in extracellular vesicles. How these distinct fates are orchestrated is unknown. Here, we show that clathrin is first recruited to TCR microclusters by HRS and STAM2 to initiate release of TCR in extracellular vesicles through clathrin- and ESCRT-mediated ectocytosis directly from the plasma membrane. Subsequently, EPN1 recruits clathrin to remaining TCR microclusters to enable trans-endocytosis of pMHC-TCR conjugates from the APC. With these results, we demonstrate how clathrin governs bidirectional membrane exchange at the immunological synapse through two topologically opposite processes coordinated by the sequential recruitment of ecto- and endocytic adaptors. This provides a scaffold for direct two-way communication between T cells and APCs

Business Process Management 2015 : Status quo und Best Practices «Prozessintelligenz»

Mehr als 40 Prozent der Unternehmen nutzen keine operativen Prozessdaten, um die Durchlaufzeiten oder Kosten ihrer Prozesse effektiv zu überwachen. Dennoch geben mehr als 60 Prozent der Unternehmen an, mit Prozessmanagement ihre Effizienz steigern zu wollen. Dies zeigt die Studie «Business Process Management 2015» der ZHAW School of Management and Law (SML). Die Ergebnisse wurden heute am BPM Symposium in Winterthur vorgestellt und mit einem breiten Fachpublikum aus Praxis und Wissenschaft diskutiert. Grundlage für die digitale Transformation: Die Studie untersucht, wie und in welchem Ausmass Unternehmen das Standardrepertoire des Geschäftsprozessmanagements in Richtung Prozessintelligenz erweitern. Prozessintelligenz schliesst die Lücke zum operativen Geschäft und liefert eine neue Perspektive auf das Management der Geschäftsprozesse. Dabei konzentriert sie sich auf die Informationen, die in den operativen Prozessen entstehen und gebraucht werden und ist somit eine wesentliche Grundlage für die aktuell viel diskutierte digitale Transformation von Unternehmen. Um Prozesse besser verstehen, steuern und optimieren zu können, werden Methoden und Werkzeuge des Geschäftsprozessmanagements (BPM) und der Business Intelligence (BI) kombiniert. Wertvolle Erfahrungen aus der Praxis: Für die Studie wurden in einer Online-Befragung über 80 Unternehmen zum Status quo ihrer «Prozessintelligenz» befragt. Ein Praxisworkshop diente als Rahmen, um Erfolgsmuster aus fünf Fallstudien bei Roche, AXA Winterthur, der St. Galler Kantonalbank sowie den Städten Lausanne und Konstanz zu identifizieren. Der Softwarehersteller Axon Ivy und SBB Immobilien haben im Rahmen einer Studienpartnerschaft mit dem Institut für Wirtschaftsinformatik der SML und dem Institut für Prozesssteuerung der HTWG Konstanz wertvolle Praxiserfahrungen beigesteuert. Das Resultat ist eine Momentaufnahme der strategischen, analytischen und praktischen Fähigkeiten, Methoden und Werkzeuge, mit denen Organisationen ihre Geschäftsprozesse gestalten, ausführen, überwachen und fortlaufend weiterentwickeln

MESoR - Management and exploitation of solar resource knowledge

CD-ROMKnowledge of the solar resource is essential for the planning and operation of solar energy systems. A number of data bases giving information on solar resources have been developed over the past years. The result is a fragmentation of services each having each own mechanism of access and all are giving different results due to different methods, input data and base years. The project MESoR, co-funded by the European Commission, reduces the associated uncertainty by setting up standard benchmarking rules and measures for comparing the data bases, user guidance to the application of resource data and unifying access to various data bases

The white blood picture during the colic in the horse in dependence on the course of the disease

Die komplette Dissertation im pdf-Format (914.974 Bytes): kurz.pdfThe aim of this thesis was the description of the course of the white blood picture of horses suffering on colic and its presentation in numbers. The influence of the drug Buscopan® compositum which is often used in the colic therapy was examined in a test on four clinical healthy horses. Neither after one nor after two injections of Buscopan® compositum there could be realised a change of the leukocyte count in relation to the Buscopan® compositum injection in the blood samples which were taken in intervals of 4 hours. 785 blood samples were taken and evaluated on 134 horses suffering on colic which were treated in the period from 1986 till 1994 in the clinic for horses of the Free University of Berlin. The first blood sample of each horse was taken after admission into the clinic and the following were taken in intervals of four hours until the ending of the treatment. Beside of different clinical and diagnostical information the following parameters were determined: total leukocyte count, basophilic granulocytes, eosinophilic granulocytes, neutrophilic stabs, neutrophilic segmented granulocytes, lymphocytes and monocytes. The absolute number of the different white blood cells were calculated. The evaluation of the bloodsamples are as follows: 1. The average of the total leukocyte count at the time of hospitalisation (x=9,930 G/l) and during the whole time of inpatient treatment (x=9,153 G/l) was within the reference values. The number of the neutrophilic stabs was decreased. At the time of hospitalisation the number of the neutrophilic segmented granulocytes (x=6,908 G/l) was also decreased and the number of the lymphocytes (x=2,227 G/l) was increased. 2. The average leukocyte count was within the reference values in cases of spastic colics (x=9,175 G/l), obstipations of the large intestine (x=9,412 G/l) and primary meteorism (x=9,871 G/l), in intestinal ruptures (x=6,600 G/l) the leukocyte count was decreased. In cases of gastric dilatation, obstipations of the small intestine (x=12,629 G/l), volvulus (x=12,056 G/l), displacement of the large colon over the nephrosplenic ligament (x=10,810 G/l), intestinal hernias (x=11,211 G/l) and peritonitis it was increased. 3. In horses which died higher leukocyte values (x=10,006 G/l) were recognised than in those which survived the colic (x=9,903 G/l). 4. Those colic patients which where treated conservatively mostly showed lower leukocyte values (x=9,469 G/l) than those cases which later were treated surgically (x=10,523 G/l). 5. No relation could be proved between the total leukocyte count and the duration of the colic. 6. With the increase of the severity of the colic the total leukocyte count, the number of the neutropilic stabs and the segmented neutrophilic granulocytes were rising. In critical colics an increased number of leucopenic blood pictures occured, partly with a shift to the left. 7. Neutrophilia indicates an endotoxemia, however neutropenia does not exclude an endotoxemia. 8. There is a positive correlation between total leukocyte count and the absolute number of the neutrophilic granulocytes as well as a strong negative correlation between the percentage of the granulocyte and the lymphocyte count. 9. The leukocyte curves for the single horses are showing a parallel course between the leukocytes and the neutrophilic granulocytes. The curves of the neutrophils and the lymphocytes are mostly opposite. 10. The leukocyte curves for the horses suffering on a special form of colic do not show any common features. 11. In those horses which died the leukocytes mostly in the neutrophilic granulocytes show morphologic changes, in form of toxic granulations and Doehle bodies. Besides this the blood of those horses was hard to smear, which showed a considerable tendency for degeneration of the white blood cells

Experts in science and society

In today's complex world, we have come to rely increasingly on those who have expertise in specific areas and can bring their knowledge to bear on crucial social, political and scientific questions. Taking the viewpoint that experts are consulted when there is something important at stake for an individual, a group, or society at large, Experts in Science and Society explores expertise as a relational concept. How do experts balance their commitment to science with that to society? How does a society actually determine that a person has expertise? What personal traits are valued in an expert? From where does the expert derive authority? What makes new forms of expertise emerge? These and related questions are addressed from a wide range of areas in order to be inclusive, as well as to demonstrate similarities across areas. Likewise, in order to be culturally comparative, this volume includes examples and discussions of experts in different countries and even in different time periods. The topics include the roles of political experts, scientific experts, medical experts, legal experts, and more