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We discuss the problem of optimal allocation of the design points of an experiment for the case where the trials may fail with non-zero probability. Numerical results for D-optimal designs are given for estimating the coefficients of a polynomial regression. For small sample sizes these designs may deviate substantially from the corresponding designs in the case of certain response. They can be less efficient, but are less affected by failing trials. (author's abstract) / Series: Forschungsberichte / Institut für Statistik

Herzinsuffizienz ist ein weltweites Gesundheitsproblem mit hoher Morbidität und Mortalität und immer noch schlechter Prognose. Ein charakteristisches Merkmal der molekularen und damit verbundenen strukturellen Veränderungen, die der terminalen Insuffizienz vorangehen ist die durch Desensitivierungsmechanismen vermittelte Abnahme des beta-adrenergen (β-AR) Signalmoleküls zyklisches Adenosinmonophosphat (cAMP) auf der einen Seite und der gleichzeitigen Zunahme des von natriuretischen Peptiden (NP) und Stickstoffmonoxid (NO) generierten zyklischen Guanosinmonophosphat (cGMP) auf der anderen Seite. Während hohe cAMP-Spiegel im Herzen als schädlich gelten, werden cGMP-abhängige Signalkaskaden vorwiegend als protektiv verstanden. Amplitude, Lokalisation und Halbwertszeit beider Signalmoleküle werden durch spezifische Enzyme, den Phosphodiesterasen (PDE) reguliert. Unter der PDE-Superfamilie wird die Isoform PDE2 als einzige von cGMP aktiviert, um dann verstärkt cAMP abzubauen und steht damit im Zentrum eines negativen Crosstalks dieser beiden Signalwege. PDE2 ist sowohl in der humanen als auch der experimentellen Herzinsuffizienz hochreguliert und scheint dort am β-AR Desensitivierungsprozess beteiligt zu sein. Im Rahmen dieser Arbeit wurde die pathophysiologische Rolle der PDE2 im Herzen näher charakterisiert. Es wird gezeigt, dass die PDE2 nicht nur in Kardiomyozyten, sondern auch in kardialen Fibroblasten exprimiert wird. In Fibroblasten inhibieren cAMP/cGMP-Signalwege die Transformation von kardialen Fibroblasten (CF) zu Myofibroblasten (MyoCF), einem zellulären Phänotyp, der unter anderem mit der persistenten Fibrotisierung des erkrankten Herzgewebes in Verbindung gebracht wird. In CF führte eine Überexpression von PDE2 zu eine starken Abnahme der basalen und β2-AR-vermittelten cAMP-Synthese und war ausreichend, um in Abwesenheit exogener, pro-fibrotischer Stimuli die Transformation zum MyoCF zu induzieren. In Übereinstimmung zeigten funktionale Analysen mit künstlich hergestelltem Bindegewebe aus PDE2-überexprimierenden CF eine deutliche Zunahme der Gewebssteifigkeit. PDE2 übte keinen Einfluss auf basale oder durch das atriale NP generiertes cGMP aus und reduzierte nur partiell die NO-induzierte cGMP-Akkumulation. Interessanterweise waren beide Stimuli in der Lage, trotz niedriger cAMP-Spiegel die PDE2-induzierte CF-Transformation zum MyoCF zu verhindern und lassen daher eine Redundanz dieser beiden sonst so gegensätzlichen Signalwege vermuten. Zur Untersuchung von PDE2 in Kardiomyozyten wurde ein transgenes (TG) Mausmodell mit spezifischer kardialer Überexpression herangezogen. Die Basalcharakterisierung zeigte eine erniedrigte Herzfrequenz (HR) mit kompensatorisch erhöhter, basaler Kontraktionskraft, sowie eine verminderte Maximalantwort bezüglich der HR nach akuter β-AR Stimulation. Auf molekularer Ebene war dieser Phänotyp mit einer verminderten Phosphorylierung verschiedener β-AR Zielstrukturen wie Troponin I, Phospholamban und Ryanodinrezeptor-2 assoziiert. Langzeitstudien belegten, dass eine Überexpression von PDE2 keine pathologischen Konsequenzen hat, sondern im Gegenteil die durchschnittliche Lebensspanne der Tiere eher verlängerte. Erste Studien im Herzinsuffizienzmodel der transversalen Aortenkonstriktion (TAC) zeigten bisher eine beständig erniedrigte HR und verminderte Wanddicken bei allerdings vergleichbarer Abnahme der kardialen Kontraktionskraft. Trotz der klaren Befunde und neuen Erkenntnisse über die vielfältige Rolle der PDE2 im Herzen lässt sich bisher noch nicht klar belegen, ob eine zusätzliche Aktivierung von myokardialen PDE2 tatsächlich im Sinne einer intrazellulären β-AR-Blockade die Progression zur Herzinsuffizienz verlangsamen oder verhindern könnte. Weitere darauf aufbauende Untersuchungen, wie z.B. eine akut induzierbare Aktivierung bzw. Deaktivierung in experimentellen Herzinsuffizienzmodellen könnten den Weg für die Entwicklung klinisch anwendbarer Ansätze zur therapeutischen Modulation dieser viel versprechenden Zielstruktur ebnen.

No / Social work is a gendered activity, in terms of both its workforce and client group and it is well documented that more women than men enter this area of work. Recruitment campaigns have had some success in attracting underrepresented groups to apply for social work training. However, achievement and retention data maintained and monitored by the General Social Care Council (GSCC) revealed that certain students did not progress as well as others. The GSCC commissioned research to consider students' progression and success rates on courses of study in England. Although the majority of students and qualified social workers are female, there have been higher relative numbers of men who fail social work training courses. This article will examine the literature and draw on material gathered from interviews with six experienced practice educators about their observations of assessing both male and female students in order to identify any factors or themes that contribute to men being overrepresented amongst those failing.

<p>The challenge for any teacher in physical education lies within being able to stimulate students who do no like physical activities or for some other reason decides not to participate. The aim of this study was to examine factors within physical education that could be the reason for students not participating and what could be done better in order to stimulate the less motivated. The study is based on interviews with ten students that went to school in two different counties. They did not consider their level of interest in sports to be influenced by their family or friends. They pointed out other factors that had been the reason for them failing Physical education. The results show that the students, mainly the girls, felt that the problem was within the corriculum, not in the syllabus. For the most part they wanted more variaty, strenght training and also a different kind of group formation. Girls also prefered more individual sports, such as different kinds of dances over too much ballgames. The students wanted the subject to teach them more about things they could benefit from in the future. The conclusion was that it would be good for the students to be divided into groups that have the same aims and interests, if possible. The teacher had a big responsibility as well as the time-schedules.</p>

Im Jemen schwelt es. Gerade in diesen Tagen werden wir mit Schrecken an die prekäre Lage des Landes erinnert. Die Wiedervereinigung des Jemen 1990 war ein wichtiger Schritt hin zur Stabilisierung. Dennoch existieren viele Probleme, deren Lösung für die Entwicklung des Landes und seine Sicherheit relevant sind. Die Autorin, seit 2007 selbst in Sanaa tätig, zeigt die Probleme des Landes und ihre vielschichtigen Ursachen auf.

The challenge for any teacher in physical education lies within being able to stimulate students who do no like physical activities or for some other reason decides not to participate. The aim of this study was to examine factors within physical education that could be the reason for students not participating and what could be done better in order to stimulate the less motivated. The study is based on interviews with ten students that went to school in two different counties. They did not consider their level of interest in sports to be influenced by their family or friends. They pointed out other factors that had been the reason for them failing Physical education. The results show that the students, mainly the girls, felt that the problem was within the corriculum, not in the syllabus. For the most part they wanted more variaty, strenght training and also a different kind of group formation. Girls also prefered more individual sports, such as different kinds of dances over too much ballgames. The students wanted the subject to teach them more about things they could benefit from in the future. The conclusion was that it would be good for the students to be divided into groups that have the same aims and interests, if possible. The teacher had a big responsibility as well as the time-schedules.

I uppsatsen presenteras en möjlighet för dominerande företag att missbruka sin marknadsställning i syfte att kringgå existerande koncentrationsförbud. Konsekvenserna för det dominerande tillika missbrukande företaget behöver nödvändigtvis inte bli så kännbara som en läsare kanske inledningsvis antar. I arbetet presenteras även en lösning på detta problem.

The ramifications of school decline are profoundly serious for the students, staff and community of a school. School decline is the steady downwards spiral that some schools experience when a complex set of influences interact with negative and unresolved outcomes. This study explored the largely unresearched area of school decline and developed a set of potential predictors of decline that could assist in understanding, preventing or dealing effectively with school decline in the future. Grounded theory, selected as a methodology appropriate for exploratory research, was used to guide the process of data collection and theory development. Three schools, labeled by agencies and the media as being in serious decline or “failing”, were selected for the study. Adults who were in significant roles in the schools during the decline periods were interviewed about their experiences. As part of the data analysis and interpretation a set of propositions was drafted and was sent to these interviewees and to fourteen educational advisors who work with schools at risk and in decline. The advisors’ feedback on the propositions, analysis of school related documents, Education Review Office reports and Ministry of Education file documents provided rich additional data. The factors associated with the lead up to school decline, and the process of decline, are multilayered, contextual and complex. Each study school’s experience of decline involved a unique combination and order of occurrence of common factors and influences. Many of the issues that predispose schools towards decline are associated with, and are exacerbated by, unethical or unprofessional attitudes or behaviour by individuals, and unprofessional practices within the schools and between neighbouring schools. Once decline begins it escalates and is difficult to stop. This thesis contributes towards the development of a theory of school decline by identifying potential predictors of school decline and by describing how decline begins and escalates. It also identifies factors that are associated with interventions being insufficient or ineffective. The theory of school decline provides insights for school leaders and educational agencies that may assist in the prediction and prevention of school decline in the future.