Dynamik der cGMP-Synthese in Sehzellen - Regulation membranständiger Guanylatzyklasen durch modifizierte Kalzium-Sensor-Proteine

Membrane bound guanylate cyclases GC1 and GC2 are important for the phototransduction in photoreceptors. They regulate, in an interplay with a phosphodiesterase, the concentration of the intracellular messenger cyclic guanosine monophosphate (cGMP). At low calciumconcentrations both GCs are activated by guanylate cyclase activating proteins (GCAP1 and GCAP2). The cGMP-concentration increases and the photoreceptor adapts. If GCs become activated a GC-dimer forms a complex with an unidentified number of GCAPs. The stoichiometry and calcium dependent conformational changes within this complex are unknown. GCAP2 has three cysteine residues, interestingly one in the first and one in the third calcium-binding-motif (EF-hand-motif). In this work cysteine mutants of GCAP2 were generated, heterologously expressed, and purified. All cysteine mutants exhibited EC50- and IC$_{50}$-values comparable to GCAP2-wildtype. However, mutants with no cysteine residue in the first EF-Hand-motif activated GCs weaker compared to GCAP2-wildtype. This indicates an important function of this cysteine residue in GC-regulation. In further experiments I investigated the accessibility of cysteine residues for the thiolreactive substance 5,5'-Dithiobis(2-nitrobenzoic acid). The cysteine residues within the first and third EF-hand-motif were only accessible at low calcium concentrations. This was surprising because the first EF-hand-motif is assumed to bind calcium with only very low affinity. Thus no calcium induced conformational change was expected. By determining the calcium sensitivities of the DTNB-reaction, which could be interpreted as apparent calcium affinities of the EF-hand-motifs, I was able to develop following model: calcium dissociation from the third EF-hand-motif in GCAP2 induces a conformational change that causes GC-activation. Furthermore I demonstrated that magnesium increases the apparent calcium affinities of the first EF-hand-motif in GCAP2 and of the first and third EF-hand-motif in GCAP1. I coupled thiolreactive dyes to cysteine mutants of GCAP2. Thereby I wanted to detect conformational changes in the vicinity of the dye. Furthermore, by recording Förster Resonance Energy Transfer between dye labeled GCAP1- and GCAP2-mutants I wanted to show the simultaneous binding of both GCAP isoforms to GC1. Both experimental approaches gave negative results. Using a soluble, enzymatic active GC1-construct instead of wildtype GC1 produced also not the expected results

Heterotopia and cultural activism – the case of Hamburg’s Gängeviertel

This paper investigates the Gängeviertel movement in Hamburg and the place which the activists have (re)constructed since its occupation in 2009 through the lens of Foucault’s (1986) concept of heterotopia. In the light of the recent debate about the role of cultural activism in the contemporary struggle about urban development, it explores the question which spatial practices and structures have evolved as oppositional to or in alignment with the neoliberal status quo of Hamburg’s spatial policy. Based on a qualitative case-study approach, the research was carried out in 2013. By using the analytical categories built environment, social practice and neoliberal normalisation, it illustrates that the Gängeviertel is characterised by practices that position it simultaneously both in- and outside of the neoliberal logic

Analisis Tindak Tutur Ilokusi pada Teks Drama Komedi Program Ado-Ado Ajo TVRI Bengkulu

ABSTRACT: Analysis of Illocutionary Speech Acts in Comedy Drama Text Program "Ado-Ado Ajo" TVRI Bengkulu. This study aims to analyze the dominant illocutionary speech acts in the comedy drama text of TVRI Bengkulu's "Ado-Ado Ajo" program and explore their functions and effects in creating humor. In this study, a qualitative approach was used by collecting data from the text transcripts of the comedy drama "Ado-Ado Ajo" TVRI Bengkulu. The collected data were then analyzed using a descriptive-interpretative method by identifying the forms and functions of illocutionary speech acts, and the dominant illocutionary speech acts in the drama script. The results showed that the most dominant illocutionary speech act in the comedy drama text of the program "Ado-Ado Ajo" is an expressive illocutionary act which states or shows the speaker's psychological attitude towards the situation implied in the illocutionary act. Based on the results of the research that has been done, it can be concluded that there is the use of illocutionary speech acts in the text of the drama script "Ado-Ado Ajo" TVRI Bengkulu. With this research, the researcher hopes to serve as a reference for further research and become learning material for the researchers themselves or for readers

Milner and the mind of imperialism

African Studies Seminar series. Paper presented 26 February 1979Capitalist development in Southern Africa, particularly in Kimberley and on the Rand, was very much the result of the penetration of British and foreign capital as well ac the rapid growth of commercial interests. The continued expansion of the mining industry, with its huge amounts of initial capital outlay, particularly after 1893 when the deep levels came into operation, depended upon the state of the capital markets of Europe: speculative booms in "kaffir" shares not only lined the pockets of investors but also provided new working capital, for little capital was raised by the issue of debentures, (l)

Szenarienanalyse im Quartier Zur methodischen Umsetzung in den Projekten „Pflege im Quartier“ und „QuartiersNETZ"

Die Szenarienanalyse wird als Instrument zur Erleichterung von Handlungsentscheidungen vorgestellt und von anderen Instrumenten der Vorausschau abgegrenzt. Die Vorgehensweise bei der Anwendung einer Szenarienanalyse wird in vier wesentliche Schritte unterteilt beschrieben. Einsatzbereiche und –möglichkeiten für Szenarien werden exemplarisch aufgezeigt. Die Anwendung einer Szenarienanalyse wird anhand der Projekte „Pflege im Quartier (PiQ)“ und „QuartiersNETZ“ veranschaulicht. Der Beitrag liefert hiermit zwei konkrete Beispiele für die unterschiedlichen Herangehensweisen und Einsatzmöglichkeiten dieses Instruments der Zukunftsforschung.This paper introduces the scenario approach as an instrument of decision making relief in various contexts, as it differentiates from other instruments of future research. The scenario analysis distinguishes between four different steps of action. Furthermore, potential fields and possibilites of application of scenarios are showcased. The scenario analysis approach is described in detail using two different research projects: „Pflege im Quartier (PiQ)“ and „QuartiersNETZ“. Hence, this paper discusses different operational areas and practical approaches for this instrument of future research using two research projects as examples

Predictive value of obsessive-compulsive drinking scale (OCDS) for outcome in alcohol-dependent inpatients: results of a 24-month follow-up study

<p>Abstract</p> <p>Background</p> <p>The present study examined whether craving as measured by the obsessive-compulsive drinking scale (OCDS) predict long-term outcome in alcohol-dependent inpatients.</p> <p>Methods</p> <p>This was a 24-month prospective, observational study in 198 alcohol-dependent inpatients treated under standardized conditions. The primary outcome criterion was abstinence, defined as no subjective report or objective indication of alcohol consumption since discharge from treatment. The patients self-rated their craving for alcohol at the 6- and 12-month follow-ups by using the German version of the OCDS, which measures obsessive and compulsive aspects of craving. Univariate and logistic regression analyses with covariates were performed.</p> <p>Results</p> <p>Of the 104 patients interviewed at the 24-month follow-up, 60% (<it>n </it>= 62) were abstinent. We found significant associations between total OCDS scores at 6 months and outcome at 12 months and between total OCDS scores at 12 months and outcome at 24 months: the higher the OCDS total score at one follow-up evaluation, the less likely patients were to be abstinent at the subsequent one. The same association was found for each of the two OCDS subscales, control and consequences and drinking obsessions.</p> <p>Conclusions</p> <p>These results support earlier findings that OCDS scores can predict outcome in alcohol-dependent patients. This information can be used for the timely development of protective resources. Hence, decisions over the use of resources can be made on the basis of objectified parameters to develop a personalized treatment concept. Consequently, economic considerations can induce a reduction of high medical costs.</p

Transdisziplinäre Forschung in der Gesundheitsförderung bei Studierenden : ein systematisches Review

Hintergrund: Der Studienalltag ist durch Bewegungsmangel und hohe Sitzzeiten gekennzeichnet, was sich negativ auf die Gesundheit auswirkt. Die Implementierung von nachhaltigen Programmen zur Bewegungsförderung an Hochschulen gewinnt somit an Bedeutung. Es mehren sich wissenschaftliche Hinweise, dass Interventionen dann erfolgreich sind, wenn transdisziplinäre Methoden angewendet werden. Fragestellung: Der Beitrag untersucht, welche Rolle transdisziplinäre Methoden bei der Entwicklung und Implementierung von gesundheitsfördernden Interventionen im Setting Hochschule bei Studierenden spielen und wie diese nachhaltig umgesetzt werden können. Methodik: Es wurde ein systematisches Literaturreview deutsch- und englischsprachiger Studien durchgeführt. Entscheidend war, dass die Studien transdisziplinäre Interventionsansätze aufweisen sowie das Bewegungs- und Sitzverhalten von Studierenden berücksichtigen. Ergebnisse: Von den 1211 identifizierten Datensätzen erfüllen 10 Studien die Auswahlkriterien. 3 Studien zielen auf eine Bewegungsförderung oder Sitzzeitreduktion ab, während 7 Studien allgemeine Gesundheitsförderung anstreben, bei der bewegungsfördernde Maßnahmen im Vordergrund stehen. Die Interventionstechniken sind Partizipation und Empowerment (n= 10), kooperative Planung (n= 8), interaktiver Wissensaustausch (n= 8) und Kapazitätsaufbau (n= 8). Schlussfolgerung: Die Ergebnisse deuten darauf hin, dass die Anwendung von transdisziplinären Methoden zu mehr Akzeptanz und einer nachhaltigeren Etablierung führt. Weitere Studien sind erforderlich, um die Wirksamkeit von Interventionen unter Anwendung transdisziplinärer Methoden zu erforschen. Für transdisziplinäre Studien zur Verringerung des sitzenden Verhaltens von Studierenden besteht weiterer Forschungsbedarf

Processing and tracking human motions using optical, inertial, and depth sensors

The processing of human motion data constitutes an important strand of research with many applications in computer animation, sport science and medicine. Currently, there exist various systems for recording human motion data that employ sensors of different modalities such as optical, inertial and depth sensors. Each of these sensor modalities have intrinsic advantages and disadvantages that make them suitable for capturing specific aspects of human motions as, for example, the overall course of a motion, the shape of the human body, or the kinematic properties of motions. In this thesis, we contribute with algorithms that exploit the respective strengths of these different modalities for comparing, classifying, and tracking human motion in various scenarios. First, we show how our proposed techniques can be employed, e.g., for real-time motion reconstruction using efficient cross-modal retrieval techniques. Then, we discuss a practical application of inertial sensors-based features to the classification of trampoline motions. As a further contribution, we elaborate on estimating the human body shape from depth data with applications to personalized motion tracking. Finally, we introduce methods to stabilize a depth tracker in challenging situations such as in presence of occlusions. Here, we exploit the availability of complementary inertial-based sensor information.Die Verarbeitung menschlicher Bewegungsdaten stellt einen wichtigen Bereich der Forschung dar mit vielen Anwendungsmöglichkeiten in Computer-Animation, Sportwissenschaften und Medizin. Zurzeit existieren diverse Systeme für die Aufnahme von menschlichen Bewegungsdaten, welche unterschiedliche Sensor-Modalitäten, wie optische Sensoren, Trägheits- oder Tiefen-Sensoren, einsetzen. Alle diese Sensor-Modalitäten haben intrinsische Vor- und Nachteile, welche sie befähigen, spezifische Aspekte menschlicher Bewegungen, wie zum Beispiel den groben Verlauf von Bewegungen, die Form des menschlichen Körpers oder die kinetischen Eigenschaften von Bewegungen, einzufangen. In dieser Arbeit tragen wir mit Algorithmen bei, welche die jeweiligen Vorteile dieser verschiedenen Modalitäten ausnutzen, um menschliche Bewegungen in unterschiedlichen Szenarien zu vergleichen, zu klassifizieren und zu verfolgen. Zuerst zeigen wir, wie unsere vorgeschlagenen Techniken angewandt werden können, um z.B. in Echtzeit Bewegungen mit Hilfe von cross-modalem Suchen zu rekonstruieren. Dann diskutieren wir eine praktische Anwendung von Trägheitssensor-basierten Eigenschaften für die Klassifikation von Trampolinbewegungen. Als einen weiteren Beitrag gehen wir näher auf die Bestimmung der menschlichen Körperform aus Tiefen-Daten mit Anwendung in personalisierter Bewegungsverfolgung ein. Zuletzt führen wir Methoden ein, um einen Tiefen-Tracker in anspruchsvollen Situationen, wie z.B. in Anwesenheit von Verdeckungen, zu stabilisieren. Hier nutzen wir die Verfügbarkeit von komplementären, Trägheits-basierten Sensor-Informationen aus

Requirements for Product Development Self-Assessment Tools

The successful execution of complex PD projects still poses major challenges for companies. One approach companies can use to improve their performance is self-assessment tools to optimize their organization and processes. This paper investigates the requirements regarding self-assessment tools for PD organizations. It summarizes the current literature on PD-related self-assessment tools and derives tool requirements from an industry focus group (US aerospace and defense industry) as well as from interviews at a major American defense contractor. The resulting requirements are: 1. Focus on proven PD best practices; 2. Formalized implementation process; 3. Tool customization guidelines; and 4. Integration with other process improvement approaches. A gap analysis comparing these requirements to the previously identified tools is performed. The paper concludes with the outline of an example PD self-assessment tool that addresses these requirements.Massachusetts Institute of Technology. Lean Advancement InitiativeCenter for Clean Water and Clean Energy at MIT and KFUP