Anlass der vorliegenden Arbeit war die Suche nach einem geeigneten Sehnendefekt-Modell, das die Untersuchung der Wirkung moderner Therapieansätze unter Standardbedingungen ermöglicht. Die Auswertung der Literatur zeigte, dass eine große Anzahl an Sehnendefekt-Modellen mit sehr unterschiedlichen Fragestellungen sowohl an Großtieren, Kleintieren als auch Labortieren eingesetzt wurde. In der vorliegenden Arbeit wurden bekannte Sehnendefekt-Modelle mit besonderem Augenmerk auf die verwendete Methodik und das damit induzierte Schadmuster untersucht. Die umfassende Literaturauswertung mit präziser pathomorphologischer Charakterisierung der Defekte diente als entscheidende Grundlage für die Entwicklung des eigenen Tiermodells. Beim hier vorgestellten Schafmodell handelt es sich um ein Core Lesion- Modell. Es simuliert die am häufigsten beim Pferd auftretende Sehnenerkrankung und bietet die Möglichkeit der direkten intraläsionalen Injektion eines Therapeutikums. Die Core Lesion stellt ein abgeschlossenes Kompartiment dar, so dass keine Trägermaterialien nötig sind, um ein appliziertes Therapeutikum am Wirkort zu binden. Verschiedene chirurgische Zugänge und Zielsehnen wurden beim Schafmodell untersucht. Als geeignet für ein Core Lesion- Modell erwiesen sich beim Schaf die tiefe Beugesehne distal des Karpalgelenks sowie die oberflächliche Beugesehne im Bereich des Tendo calcaneus communis. Für die Induktion der Läsion wurden in Anlehnung an die von LITTLE und SCHRAMME (2006) bzw. SCHRAMME et al. (2010a) beim Pferd gezeigte Methodik unterschiedliche chirurgische Instrumente verwendet. Dabei wurden der Einsatz einer Knochenmark-Extraktionsnadel sowie verschiedene manuell oder elektrisch betriebene arthroskopische Klingen und Fräsköpfe hinsichtlich ihrer Verwendbarkeit sowie des durch sie verursachten Schadmusters miteinander verglichen. Ein manueller Instrumenteneinsatz führte zu deutlich milderen Schadmustern. Dabei kam es durch die Verwendung des Stiletts einer Knochenmark-Extraktionsnadel in einigen Bereichen zu scharfen Faserdurchtrennungen, in anderen Bereichen wurden die Kollagenfasern nur stumpf auseinander gedehnt. Der Einsatz arthroskopischer Klingen und Fräsköpfe beim Schafmodell ist nur eingeschränkt möglich. Durch die geringe Sehnengröße stehen nur sehr wenige Instrumente mit einem entsprechend kleinen Durchmesser zur Verfügung. Ein Round Burr konnte unter experimentellen Bedingungen eingesetzt werden und führte zu einer hochgradigen Schädigung des kompletten Sehnenquerschnitts. Dabei wurden die Fasern aus ihrer ursprünglichen Orientierung heraus gerissen, zumeist aber nicht vom umgebenden Gewebe abgetrennt. Ein Synovial Resector führte hingegen zu einer scharfen Faserdurchtrennung und dadurch zu einem deutlich abgegrenzten Defektbereich. Weitere Einzelheiten wie die resultierende Einblutung und das Einwandern verschiedener Entzündungszell-Spezies müssen in-vivo untersucht werden, um eine klare Empfehlung für den Einsatz der verschiedenen Instrumente formulieren zu können. Die Auswertung der vorhandenen Sehnendefekt-Modelle sowie die eigenen Ergebnisse führten zu dem Schluss, dass eine Kombination verschiedener Methoden sinnvoll sein könnte. Die Arbeit beschreibt ein sicheres, praktikables Großtiermodell für die Simulation von Core Lesions. Das Modell kann zunächst im Tierversuch eingesetzt werden, um die nach Defektinduktion ablaufenden pathophysiologischen Prozesse zu charakterisieren. Dann steht mit dem Schafmodell ein zeitgemäßes Modell für die Untersuchung verschiedener Therapiekonzepte zur Verfügung, das für die Pferdemedizin eingesetzt werden kann, sich aber auch für Untersuchungen mit humanmedizinischem Hintergrund vielversprechend zeigt. Das Modell stellt damit ein wichtiges Bindeglied zwischen Grundlagenforschung und dem klinischen Einsatz moderner Therapiekonzepte dar.

Understanding complex Earth systems is challenging for scientists and students alike, because of the characteristics (e.g. bifurcations, self-organization, chaotic response) that are associated with these systems. This research integrates two research strands which contribute to the scientific and pedagogical understanding of complex Earth systems. In the first strand, a method that characterizes volatile organic compounds (VOCs) as ecological proxies of soil microbial ecosystems was validated. Unlike other measures of microbial community structure (e.g. Biolog and FAME), VOCs are advantageous because they are non-destructive and can provide temporal and spatial data. Additionally they are rich sources of information that describe the microbial metabolism, community structure, and organic carbon substrates utilized by soil microorganisms. Statistical results indicate that the detected and identified VOCs were significant (p < 0.05) indicators of microbial community composition shift in soil microcosm studies. Geographical information systems (GIS) illustrates that VOCs varied with space and time in south Texas soils. The second strand focuses on a geoscience education study exploring student conceptual model development of complex Earth systems. The efficacy of multiple representations and inquiry was tested as the pedagogical strategy in upper and lower level undergraduate courses to support students’ conceptual model development of complex Earth systems. Comparisons in student performance were based on prior knowledge (low and high) and on exposure to the implemented pedagogy (control and experimental groups). Results indicate that an inquiry-based learning model coupled with the use of multiple representations had significant positive performance impacts on students’ conceptual model development and content knowledge. This dissertation model integrates science and education research and is particularly useful for graduate students who intend to pursue a career in academia and envision teaching as part of their professional duties. It allows for synergy between teaching and research to be achieved where the classroom becomes a laboratory for research. Ultimately, the research conducted in the classroom informs pedagogy and enhances scholarship. Graduates learn to bridge the gap between education and science departments where they become leaders in science who conduct cutting-edge scientific research and also value making a broader impact on society through enhancing public education.

<p>The difficulties of system design are persistentlyincreasing due to the integration of more functionality on asystem, time-to-market pressure, productivity gap, andperformance requirements. To address the system designproblems, design methodologies build system models at higherabstraction level. However, the design task to map an abstractfunctional model on a system architecture is nontrivial becausethe architecture contains a wide variety of system componentsand interconnection topology, and a given functionality can berealized in various ways depending on cost-performancetradeoffs. Therefore, a system design methodology must provideadequate design steps to map the abstract functionality on adetailed architecture.</p><p>MASIC—Maths to ASIC—is a system design methodologytargeting DSP applications. In MASIC, we begin with afunctional model of the system. Next, the architecturaldecisions are captured to map the functionality on the systemarchitecture. We present a systematic approach to classify thearchitectural decisions in two categories: system leveldecisions (SLDs) and implementation level decisions (ILDs). Asa result of this categorization, we only need to consider asubset of the decisions at once. To capture these decisions inan abstract way, we present three transaction level models(TLMs) in the context of DSP systems. These TLMs capture thedesign decisions using abstract transactions where timing ismodeled only to describe the major synchronization events. As aresult the functionality can be mapped to the systemarchitecture without meticulous details. Also, the artifacts ofthe design decisions in terms of delay can be simulatedquickly. Thus the MASIC approach saves both modeling andsimulation time. It also facilitates the reuse of predesignedhardware and software components.</p><p>To capture and inject the architectural decisionsefficiently, we present the grammar based language of MASIC.This language effectively helps us to implement the stepspertaining to the methodology. A Petri net based simulationtechnique is developed, which avoids the need to compile theMASIC description to VHDL for the sake of simulation. We alsopresent a divide and conquer based approach to verify the MASICmodel of a system.</p><p><b>Keywords:</b>System design methodology, Signal processingsystems, Design decision, Communication, Computation, Modeldevelopment, Transaction level model, System design language,Grammar, MASIC.</p>

El desarrollo conducido por modelos o Model-Driven Development (MDD) es una aproximación a la Ingeniería de Software cuyo concepto central son los modelos y sus respectivas transformaciones. MDD brinda los principios básicos que permiten visualizar un sistema de software como un conjunto de modelos que son sucesivamente refinados hasta alcanzar uno con el suficiente nivel de detalle como para ser implementado. La Arquitectura Conducida por Modelos o Model-Driven Architecture (MDA) es la propuesta del Object Management Group (OMG) para MDD. Su objetivo fundamental es separar la especificación de la funcionalidad del sistema de la especificación de la implementación de dicha funcionalidad sobre una plataforma específica. La trazabilidad, como propiedad deseable de toda transformación de modelos, tiene un rol fundamental dentro del paradigma dado que la misma permite, entre otras cosas, la posibilidad de evaluar el impacto en fases avanzadas del ciclo de vida ante cambios en los requerimientos elicitados en etapas tempranas, y el mantenimiento de la consistencia entre los distintos modelos que guían el desarrollo. Este trabajo propone un esquema que permite la obtención de información de trazabilidad a partir de la definición de una transformación de modelos escrita en lenguaje QVT Relations mediante la utilización de una estrategia de inferencia de trazas definida ad hoc. Dicho proceso es totalmente automático y no depende de la ejecución de la transformación. Las principales contribuciones del estudio incluyen la minimización de los esfuerzos manuales en la gestión de trazabilidad, actividad tediosa y muy propensa a errores, y la independencia respecto de la implementación del motor QVT. / Model-driven development (MDD) is a Software Engineering approach consisting of models and their transformations. MDD gives the basic principles to visualize a software system as a set of models that are repeatedly refined until a model with enough details to implement. Model-driven architecture (MDA) is the MDD view of Object Management Group. MDA main goal is to separate the system functional specification from the implementation specification on an given platform. Traceability, as a desired feature of transformations, has a major role within the paradigm since it allows the possibility to evaluate the impact at advanced stages of changes in requirement specification elicited early, and keeping consistency between models that guide the development, among other benefits. This work proposes a framework to get traceability information from a transformation definition written in QVT Relations language using a trace inference strategy defined ad hoc. This process is fully automated and does not depend on the execution of transformation. The contributions of the work include the minimization of manual efforts to achieve traceability, as error-prone and time-consuming activity, and the attainment of independence regarding the QVT engine implementation.

Effectiveness and usefullness among the important factors that affect success of online learning environments. During this study, a course-content management system developed regarding effectivity and usability related concerns. One major aim of this study is to develop effective and usable system. In this study, a course-content management system designed and developed under the light of previous researches. In the design phase, effective design strategies and characteristics of effective and usable learning systems were explored, and system was designed considering these strategies. Then, development phase applied. After system developed, usability techniques was explored, and heuristic evaluation method was choosed as a usability method to measure usability of the system. During the study, modified version of a checklist that was prepared considering usability heuristics. Applied checklist contains total 108 questions under 13 heuristics (major usability problem). Heuristic evaluation is an expert review method. Therefore, this study should have been evaluated by experts. 8 experts enrolled in this study. All experts are either Phd or graduate students at instructional technology departments and they have enrolled in web-based studies. They investigated the usability of the course-content management system according to the usability related criterias on the checklist. When test results were considered, a course-contentmanagement system developed during this study was found usable. Results of this study may enlighten the way of future studies.

Model development decisions are an important feature of engineering design. The quality of simulation models often dictates the quality of design decisions, seeing as models guide decision makers (DM) in choosing design decisions. A quality model accurately represents the modeled system and is helpful for exploring what-if scenarios, optimizing design parameters, estimating design performance, and predicting the effect of design changes. However, obtaining a quality model comes at a cost in terms of model development--in experimentation, labor, model development time, and simulation time. Thus, DMs must make appropriate trade-offs when considering model development decisions. The primary challenge in model development is making decisions under significant uncertainty. This thesis addresses model development in the conceptual design phase where uncertainty levels are high. In the conceptual design phase, there are many information constraints which may include an incomplete requirements list, unclear design goals, and/or undefined resource constrains. During the embodiment design phase, the overall objective of the design is more clearly defined, and model development decisions can be made with respect to an overall objective function. For example, the objective may be to maximize profit, where the profit is a known function of the model output. In the conceptual design phase, this level of clarity is not always present, so the DM must make decisions under significant model uncertainty and objective uncertainty. In this thesis, conjoint analysis is employed to solicit the preferences of the decision maker for various model attributes, and the preferences are used to formulate a quasi-objective function during the conceptual design phase--where the overall design goals are vague. Epistemic uncertainty (i.e., imprecision) in model attributes is represented as intervals and propagated through the proposed model development framework. The model development framework is used to evaluate the best course of action (i.e., model development decision) for a real-world packaging design problem. The optimization of medical product packaging is assessed via mass spring damper models which predict contact forces experienced during shipping and handling. Novel testing techniques are employed to gather information from drop tests, and preliminary models are developed based on limited information. Imprecision in preliminary test results are quantified, and multiple model options are considered. Ultimately, this thesis presents a model development framework in which decision makers have systematic guidance for choosing optimal model development decisions.

Philosophiae Doctor - PhD / The mental health care environment is a stressful environment because of the environment, perceived unpreparedness of students and the emotional demands placed on the students which are inherent in the nature of the work. The use of the self as a therapeutic tool also presents challenges for students. Whilst researchers have identified supportive interventions and strategies to address students support needs in mental health care settings, these interventions/strategies focus on meeting clinical learning objectives with the assumption that if the student learning needs are met, they will feel emotionally supported. Literature and experience indicates that it is imperative that in this field of study, students should be prepared to cope emotionally with the demands of mental health work. The aim of this research was to develop a model of emotional support for student nurses working in mental health care settings. A theory-generating design based on a qualitative, explorative and descriptive research approach was used to achieve the aim of the study. Purposive sampling was employed to select participants namely: students, educators and clinical staff who met the eligibility criteria. A sample of 40 students, nine educators and nine clinical staff who worked in the four psychiatric hospitals and community mental health clinics in the Western Cape participated in the study. Data collection was by means of focus group interviews (students) and indepth individual interviews (educators and clinical staff). Data was analysed by means of Tesch’s method of content analysis. The model was developed by means of the four steps of the theory generation process. Step one was concept development which consisted of two sub-steps namely concept identification and concept definition. A total of 22 concepts were identified which was further synthesised into six main concepts. The main concepts which were used to develop the model were: positive self-concept; positive work environment; academic and professional development; effective communication; formal and informal supportive interventions and collaboration between the Higher Education Institution and the mental health care setting. Step two of the theory generating process was model development. These main concepts were placed in relation with each other which formed an emotional support model for students working in mental health care settings. Step three was model description. The model was described using the three phases of interpersonal communication namely orientation phase, working phase and the termination phase. A visual application of the model which depicts the main concepts, the process and the context was shown. Step four dealt with the development of the guidelines for the implementation of the emotional support model. A critical reflection of the model was done using five criteria for model evaluation according to Chinn & Kramer. Trustworthiness of the data was ensured by means of applying Guba’ model of truth value, applicability, consistency and neutrality. Reflexivity was used by the researcher to further enhance trustworthiness. Permission to conduct the study was obtained from the relevant authorities. The ethical principles of respect for human dignity, beneficence and justice were applied throughout the study. Limitations were identified and ecommendations for nursing practice, education concluded the study.

Das Ziel des Vorhabens bestand in der Ertüchtigung von CFD-Codes für Wasser-Dampf-Strömungen mit Phasenübergang. Während CFD-Verfahren für einphasige Strömungen bereits breite Anwendung in der Industrie finden, steht ein entsprechender Einsatz für Zweiphasenströmungen auf Grund der komplexen Phasengrenzfläche und den davon beeinflussten Wechselwirkungen erst am Anfang. Für die Weiterentwicklung und Validierung geeigneter Schließungsmodelle werden experimentelle Daten mit hoher Orts- und Zeitauflösung benötigt. Solche Daten wurden an der TOPFLOW-Versuchsanlage des HZDR durch Kombination von Experimenten bei praxisnahen Parametern für die Reaktorsicherheit (große Skalen, hohe Drücke und Temperaturen) und innovativer Messtechnik gewonnen. Die Gittersensortechnik, mit der detaillierte Informationen über die Phasengrenzfläche gewonnen werden können, wurde in adiabaten Wasser-Luft-Experimenten sowie Kondensations- und Druckentlastungsexperimenten in einem großen DN200-Rohr eingesetzt. Umfangreiche Datenbasen mit hoher Qualität stehen im Ergebnis des Vorhabens zur Verfügung. Die Technologie für die schnelle Röntgentomographie, die Messungen ohne Strömungsbeeinflussung ermöglicht, wurde weiter entwickelt und in einer ersten Messserie erfolgreich eingesetzt. Hochaufgelöste Daten wurden auch in Experimenten zu verschiedenen Strömungssituationen (z.B. Gegenstrombegrenzung) in einem Modell des heißen Strangs eines Druckwasserreaktors gewonnen. Für die Wasser-Dampf-Experimente bei Drücken von bis zu 5 MPa wurde dabei erstmals die neu entwickelte innovative Drucktanktechnologie eingesetzt. Zur Ertüchtigung von CFD-Codes für Zweiphasenströmungen wurde das Inhomogene MUSIG-Modell für Phasenübergänge in Kooperation mit ANSYS erweitert und anhand der o.g. TOPFLOW-Experimente validiert. Außerdem erfolgten Verbesserungen u.a. für die Turbulenzmodellierung in Blasenströmungen sowie Simulationen zur Validierung der Modelle für Blasenkräfte und Blasenkoaleszenz und -zerfall. Ein wesentlicher Fortschritt wurde bei der Modellierung freier Oberflächen durch die Verallgemeinerung des AIAD-Modells erreicht. Die am Heißstrangmodell ermittelten Flut¬kurven können unter Nutzung dieses Modells in guter Übereinstimmung berechnet werden.

<p>The PRLs are a subfamily of dual specificity phosphatases that appear to play important roles in oncogenesis. Much of the current understanding of PRL function has been either correlative, and deduced from observed PRL overexpression in pathological conditions, or from in vitro analysis of signaling pathways following PRL deletion or overexpression. Such studies, necessitated by the general lack of synthetic inhibitors or compounds to probe the substrate specificity and biological interactions of the PRLs, are nonetheless now providing critical insight into potential biological substrates and roles of the PRL phosphatases. The recent identification of PTEN as a substrate for PRL2 provided the foundation for studies to further define the role of PRL2 in oncogenesis and, by analogy, the normal physiological function of PRL2. In the studies described herein, a novel PRL2 conditional knock-out animal was generated and used to validate the PRL2/PTEN interaction in a leukemic phenotype, and further demonstrated that PRL2 inhibition can restore dysregulated PTEN/AKT pathways to significantly attenuate disease progression. Inhibition of PRL2 therefore represents a novel potential therapeutic strategy in the management and treatment of AML. This thesis project also sought to further examine the role of the PRLs in oncogenesis through their regulation and interaction of targets within the TME. Functional analyses revealed that PRL3 was the only PRL to have a prominent role in host response to TME development, and that previously proposed roles for PRL3 in angiogenesis and immune cell recruitment is dependent upon PRL3 expression and activity in cells external to the TME. The study also revealed a previously unrecognized synergism between VEGF and PRL3 in the host in promoting TME angiogenesis. The studies of PRL3 in the TME suggest the potential physiological role of PRL3 in wound healing.</p>

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