Decapentaplegic (Dpp), a member of the TGF-[Beta] superfamily, acts as a morphogen to direct cell differentiation, determine cell fate and promote cell survival and proliferation in Drosophila wing development. To investigate the role of Dpp in Drosophila wing development, three aspects of the patterning role of Dpp have been analyzed. First, I investigated the cellular responses to Dpp signaling by a loss of function strategy. The consequences of lacking Dpp signal transduction on cell morphology and tissue integrity were analyzed. Second, I investigated whether Dpp signaling is down-stream of Hh signaling to maintain the normal cell segregation at the A/P boundary by clonal analysis. Third, I investigated whether cross talk among the Hh, Dpp and Wg signaling pathways exists and what its relevance for wing patterning is. To investigate the role of Dpp in Drosophila wing development, the general strategies are to look at the phenotypes of loss-of-function and gain-of-function. Mutant clones lacking Dpp signal transduction by knock down Dpp receptor Thick veins (Tkv) do not survive in wing blade due to JNK dependent apoptosis. To get larger mutant clones for analysis, JNK pathway was inhibited by knock down bsk (encodes JNK) in mutant clones lacking Dpp signaling using FLP-FRT system. Clones double mutant for tkv and bsk did not undergo apoptosis, but recovered at very low frequencies compared to sibling clones. Here, I showed that the low recovery of tkv bsk double mutant clones are due to the extrusion of mutant cells. The extrusion of tkv bsk double mutant cells correlated with changes in the actin cytoskeleton and a dramatic loss of the apical microtubule web normally present in these cells. These results suggest that Dpp signaling is required for cell morphogenesis in Drosophila wing development. We propose that Dpp acts as a survival factor in the wing disc epithelium by orchestrating proper cytoskeletal organization and maintaining normal cell-cell contact. Drosophila wing is subdivided into anterior (A) and posterior (P) compartments. This developing into adjacent compartments is crucial for the patterning of Drosophila wing. Previous study has shown that Hedgehog (Hh) signaling is required in A cells to maintain the A/P boundary and is sufficient to specify A type cell sorting. A previous study has in addition implicated the signaling molecule Decapentaplegic (Dpp) in maintaining the A/P boundary. However, this study did not address whether and in which cells, A and/or P, Dpp signal transduction was required to maintain this boundary. Here, I have analyzed the role of components of the Dpp signal transduction pathway and the relation of Dpp and Hh signaling in maintaining the A/P boundary by clonal analysis. I showed that Dpp signaling mediated by the Dpp target gene, T-box protein Optomotor-blind (Omb), is required in A cells, but not in P cells, to maintain the normal position of the A/P boundary. During patterning formation, it is essential for cells to receive precise positional information to pattern the tissue. It has been proposed for a long time that different signaling pathways such as Hedgehog (Hh), Dpp and Wingless (Wg) signaling pathways provide positional information for tissue patterning in an integrated manner. Recently, evidence of interactions between Hh and Dpp as well as Wg and Hh signaling pathways has been reported in Drosophila wing. Here, I have identified additional interactions among Hh, Dpp and Notch/Wg signaling. We propose that the selector gene engrailed, Hh and Dpp signaling interact with each other to regulate target genes expression and thus to pattern the wing along the A/P axis. Further more, I showed that Dpp signaling is also participating in the patterning along the D/V axis by interaction with the selector gene apterous and Notch/Wg signaling.

Myotubularins are lipid phosphatases that dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate the position three of the inositol ring. This allows them to regulate the structure of the lipid layer of the membrane compartment. The first member of the family was described in association with a severe hereditary myopathy. From that point on, another thirteen members have been added to the family. The catalytically inactive MTMR9 carrying the conserved mutation in the phosphatase domain regulates the localization of the marker of the early secretory pathway, RAB1A, the cis-Golgi structure and the secretion. MTMR9 interacts with the catalytically active MTMR6 and MTMR8 that specifically localizes and increases their phophatase activity. The aim of this diploma thesis was to find out whether the phenotype observed in cells with altered MTMR9 levels is dependent on the catalytically active phosphatases MTMR6 and MTMR8. We proved the influence of MTMR6 and MTMR8 on the distribution of tranfected RAB1A between the intermediate compartment and the Golgi apparatus. MTMR6 and MTMR8 also take part in regulating the cis-Golgi structure. By the use of two different approaches we did not manage to clarify the influence of MTMR6 and MTMR8 on secretion. Changes in the catalytic...

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21094号 / 工博第4458号 / 新制||工||1693(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 米田 稔, 教授 高岡 昌輝, 准教授 福谷 哲 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Indiana University-Purdue University Indianapolis (IUPUI) / A crucial task in computer vision and biomedical image applications is to represent images in a numerically compact form for understanding, evaluating and/or mining their content. The fundamental step of this task is the segmentation of images into regions, given some homogeneity criteria, prior appearance and/or shape information criteria. Specifically, segmentation of cells in microscopic images is the first step in analyzing many biomedical applications. This thesis is a part of the project entitled "Construction and profiling of biodegradable cardiac patches for the co-delivery of bFGF and G-CSF growth factors" funded by National Institutes of Health (NIH). We present a method that simultaneously segments the population of cells while partitioning the cell regions into cytoplasm and nucleus in order to evaluate the spatial coordination on the image plane, density and orientation of cells. Having static microscopic images, with no edge information of a cytoplasm boundary and no time sequence constraints, traditional cell segmentation methods would not perform well. The proposed method combines deformable models with a probabilistic framework in a simple graphical model such that it would capture the shape, structure and appearance of a cell. The process aims at the simultaneous cell partitioning into nucleus and cytoplasm. We considered the relative topology of the two distinct cell compartments to derive a better segmentation and compensate for the lack of edge information. The framework is applied to static fluorescent microscopy, where the cultured cells are stained with calcein AM.

Numerous prediction models of SARS-CoV-2 pandemic were proposed in the past. Unknown parameters of these models are often estimated based on observational data. However, lag in case-reporting, changing testing policy or incompleteness of data lead to biased estimates. Moreover, parametrization is time-dependent due to changing age-structures, emerging virus variants, non-pharmaceutical interventions, and vaccination programs. To cover these aspects, we propose a principled approach to parametrize a SIR-type epidemiologic model by embedding it as a hidden layer into an input-output non-linear dynamical system (IO-NLDS). Observable data are coupled to hidden states of the model by appropriate data models considering possible biases of the data. This includes data issues such as known delays or biases in reporting. We estimate model parameters including their time-dependence by a Bayesian knowledge synthesis process considering parameter ranges derived from external studies as prior information. We applied this approach on a specific SIR-type model and data of Germany and Saxony demonstrating good prediction performances. Our approach can estimate and compare the relative effectiveness of non-pharmaceutical interventions and provide scenarios of the future course of the epidemic under specified conditions. It can be translated to other data sets, i.e., other countries and other SIR-type models.

The problem facing the Tlokwe Local Municipality is that it is Constitutional and legislatively obliged to avoid and/or mitigate the impact of potential disasters within its boundaries, through the effective management of potential disaster risks and disasters. The lack of effective risk management tools is especially concerning in the context of the water catchment management of the Mooi River, which is the main water supply of the Tlokwe local Municipality. The Mooi River is exposed to many potential catchment related hazards that could affect the municipality of which the origins are both anthropogenic and natural. Although, many of the impacts on the catchment arise beyond the boundaries and the control of the municipality, this does not relieve the municipality from the responsibility to develop tools to manage the risks. The aim of the study is to assist in addressing the above stated problem through establishing the requirements for a conceptual model for an effective spatial information system that will assist the municipality in effectively managing the potential disaster risks and disasters that may arise in the Mooi River Catchment area that could impact on the Tlokwe Local Municiaplity. The aim gives rise to three-research questions that are formulated as research objectives that are used to identify the conceptual model requirements. The first is to identify and conceptualise the constitutional and legislative obligations in respect of disaster risk management in general and specifically those governing the disaster disk management in the water catchment area for the Mooi River. The study of this objective not only highlight the constitutional and legal obligations that the local municipality is subject to, but provides legislatives remedies that the local municipality can utilise to assist with disaster risks reduction. The second is to identify and conceptualise the generic hazards that are related to water catchment areas (including the related groundwater compartments) and those specific in the Mooi River catchment area. In this section, potential anthropogenic and natural hazards are listed, a methodology for risk and vulnerability analyses is provided, and a concise study of quaternary catchment C23D is provided. The third is to identify and conceptualize the requirements for an effective conceptual model of GIS for Disaster Risk Management in the Tlokwe Local Municipality. An overview of a GIS is provided. The essential components of a generic information system namely, people, software, hardware, procedures and processes, data and telecommunications or networks are discussed. The information and system requirements cumulating from the analyses of the three research questions, serve as the drivers of the goal, outcomes and transformation process of the system as well as the requirements for the conceptual model. In this section: a comparison of the Systems Development Life Cycle (SDLC), Framework for Applied Systems Thinking (FAST), problem solving and the phases addressed in this study; the identification of the conceptual model requirements; and a concise systems conceptualisation of an effective GIS is provided. As the, mini-dissertation focuses on the needs for a conceptual model, the additional activities required before the system can be implemented are identified and formulated as recommendation that provide the opportunity for future research. / M Development and Management, North-West University, Potchefstroom Campus, 2014

The problem facing the Tlokwe Local Municipality is that it is Constitutional and legislatively obliged to avoid and/or mitigate the impact of potential disasters within its boundaries, through the effective management of potential disaster risks and disasters. The lack of effective risk management tools is especially concerning in the context of the water catchment management of the Mooi River, which is the main water supply of the Tlokwe local Municipality. The Mooi River is exposed to many potential catchment related hazards that could affect the municipality of which the origins are both anthropogenic and natural. Although, many of the impacts on the catchment arise beyond the boundaries and the control of the municipality, this does not relieve the municipality from the responsibility to develop tools to manage the risks. The aim of the study is to assist in addressing the above stated problem through establishing the requirements for a conceptual model for an effective spatial information system that will assist the municipality in effectively managing the potential disaster risks and disasters that may arise in the Mooi River Catchment area that could impact on the Tlokwe Local Municiaplity. The aim gives rise to three-research questions that are formulated as research objectives that are used to identify the conceptual model requirements. The first is to identify and conceptualise the constitutional and legislative obligations in respect of disaster risk management in general and specifically those governing the disaster disk management in the water catchment area for the Mooi River. The study of this objective not only highlight the constitutional and legal obligations that the local municipality is subject to, but provides legislatives remedies that the local municipality can utilise to assist with disaster risks reduction. The second is to identify and conceptualise the generic hazards that are related to water catchment areas (including the related groundwater compartments) and those specific in the Mooi River catchment area. In this section, potential anthropogenic and natural hazards are listed, a methodology for risk and vulnerability analyses is provided, and a concise study of quaternary catchment C23D is provided. The third is to identify and conceptualize the requirements for an effective conceptual model of GIS for Disaster Risk Management in the Tlokwe Local Municipality. An overview of a GIS is provided. The essential components of a generic information system namely, people, software, hardware, procedures and processes, data and telecommunications or networks are discussed. The information and system requirements cumulating from the analyses of the three research questions, serve as the drivers of the goal, outcomes and transformation process of the system as well as the requirements for the conceptual model. In this section: a comparison of the Systems Development Life Cycle (SDLC), Framework for Applied Systems Thinking (FAST), problem solving and the phases addressed in this study; the identification of the conceptual model requirements; and a concise systems conceptualisation of an effective GIS is provided. As the, mini-dissertation focuses on the needs for a conceptual model, the additional activities required before the system can be implemented are identified and formulated as recommendation that provide the opportunity for future research. / M Development and Management, North-West University, Potchefstroom Campus, 2014

Database systems build an integral component of today’s software systems and as such they are the central point for storing and sharing a software system’s data while ensuring global data consistency at the same time. Introducing the primitives of roles and their accompanied metatype distinction in modeling and programming languages, results in a novel paradigm of designing, extending, and programming modern software systems. In detail, roles as modeling concept enable a separation of concerns within an entity. Along with its rigid core, an entity may acquire various roles in different contexts during its lifetime and thus, adapts its behavior and structure dynamically during runtime. Unfortunately, database systems, as important component and global consistency provider of such systems, do not keep pace with this trend. The absence of a metatype distinction, in terms of an entity’s separation of concerns, in the database system results in various problems for the software system in general, for the application developers, and finally for the database system itself. In case of relational database systems, these problems are concentrated under the term role-relational impedance mismatch. In particular, the whole software system is designed by using different semantics on various layers. In case of role-based software systems in combination with relational database systems this gap in semantics between applications and the database system increases dramatically. Consequently, the database system cannot directly represent the richer semantics of roles as well as the accompanied consistency constraints. These constraints have to be ensured by the applications and the database system loses its single point of truth characteristic in the software system. As the applications are in charge of guaranteeing global consistency, their development requires more effort in data management. Moreover, the software system’s data management is distributed over several layers, which results in an unstructured software system architecture. To overcome the role-relational impedance mismatch and bring the database system back in its rightful position as single point of truth in a software system, this thesis introduces the novel and tripartite RSQL approach. It combines a novel database model that represents the metatype distinction as first class citizen in a database system, an adapted query language on the database model’s basis, and finally a proper result representation. Precisely, RSQL’s logical database model introduces Dynamic Data Types, to directly represent the separation of concerns within an entity type on the schema level. On the instance level, the database model defines the notion of a Dynamic Tuple that combines an entity with the notion of roles and thus, allows for dynamic structure adaptations during runtime without changing an entity’s overall type. These definitions build the main data structures on which the database system operates. Moreover, formal operators connecting the query language statements with the database model data structures, complete the database model. The query language, as external database system interface, features an individual data definition, data manipulation, and data query language. Their statements directly represent the metatype distinction to address Dynamic Data Types and Dynamic Tuples, respectively. As a consequence of the novel data structures, the query processing of Dynamic Tuples is completely redesigned. As last piece for a complete database integration of a role-based notion and its accompanied metatype distinction, we specify the RSQL Result Net as result representation. It provides a novel result structure and features functionalities to navigate through query results. Finally, we evaluate all three RSQL components in comparison to a relational database system. This assessment clearly demonstrates the benefits of the roles concept’s full database integration.

Den här rapporten behandlar ett utvecklingsprojekt med mål att framställa ett designförslag på utformingen av ett måttdefinerat lastutrymme. Detta sker inom ramen av ett examensarbete, omfattande 22,5 hp, som en del i högskoleingenjörsprogrammet inom innovationsteknik och design på Karlstads universitet. Uppdragsgivare är Martin Larsson, vd på Precer Autotech, ett företag som utvecklar en ny typ av hybridfordon som drivs av fastbränslen. Detta fordon har dimensionerna av en normalstor personbil, men klassas som en motorcykel, eller fyrhjuling. I och med detta har fordonet i fråga speciella faktorer att förhålla sig till när det gäller bl.a. förhållandet mellan vikt och storlek. Utvecklingen av lastutrymmet är ett projekt som är med och utvecklar en grund för det framtida konceptfordon som utav Precer Autotech ska utvecklas. Den industriella designprocessen har genomsyrat projektet och metoder tillhörande denna process har betonats. Metoder såsom användningen av en fullskalig mock-up har gett detta projekt en särprägel. Från idégenereringar till konceptutvecklingar har projektet använt sig av metoder och tillvägagångssätt vilka betonats i projektansvariges universitetsutbildning. Resultatet från detta projekt har mynnat ut i ett helhetskoncept för utforming av det måttbestämda lastutrymmet, som visat sig uppfylla de krav som ställdes på den slutgiltiga konceptlösningen. Denna slutgiltiga konceptlösning har utarbetats i en fullskalig mock-up, vilket också har varit en del av projektets mål. / This report covers a development project which goal is to produce one or more layout concepts of a measure defined boot compartment. This project is conducted as Bachelor of Science thesis within the bachelor engineering program of innovation technics and design in Karlstad University, Sweden. The assignment was supplied by Martin Larsson, managing director at Precer Autotech, a company that is developing a new type of hybrid vehicle that runs on solid fuels. This vehicle owns the dimensions of an average sized car, though is technically defined as a larger sized quad or ATV. Because of this, the vehicle in question is subject to several special factors regarding, for example, the ratio between weight and size. The project is going to provide part of the foundation on which this concept vehicle will be developed. The process of industrial design has pervaded this project, with methods and techniques originated from said process riddling the entirety of the project. Methods such as the use of a full scale mock-up have nuanced this project. From sessions of brainstorming to the development of concepts, this project has been using techniques and ways which has been a defining part of the university studies. The project resulted in one concept for totality of the measure defined boot compartment, which has shown to fulfill the demands of the project. The final concept solution has also been implemented in a full scale mock-up, which was a part of the project’s goals. / Utveckling av lastutrymme för ett konceptfordon

La thèse a été réalisée dans le cadre d’un partenariat entre le laboratoire d’accueil (C2MA, IMT Mines d’Alès), l’entreprise Renault et un contrat Cifre. La prise de conscience de la dégradation de la qualité de l’air s’étend à tous les environnements, que ce soit à l’intérieur ou à l’extérieur. En Asie, cette prise de conscience se traduit par de très strictes réglementations de la qualité de l’air dans l’habitacle automobile. Les constructeurs se doivent de respecter ces nouvelles réglementations afin de pouvoir vendre leurs véhicules dans ces pays où le marché automobile est en pleine croissance (principalement en Chine). C’est dans ce contexte que Renault a décidé d’améliorer la prise en compte de la qualité de l’air habitacle dans le développement de ses véhicules. Les contraintes techniques et la numérisation des outils de travail ont orienté le travail de thèse vers la modélisation de cette qualité de l’air habitacle. Afin de pouvoir tendre vers cet objectif, plusieurs points ont été traités. Tout d’abord, l’émission des matériaux d’habitacle a été caractérisée afin de comprendre quels composés organiques volatils et quels matériaux étaient responsables de la dégradation de la qualité de l’air dans le véhicule. Ensuite, une nouvelle approche expérimentale a été développée permettant une caractérisation plus représentative de l’émission des matériaux dans l’habitacle. Ces travaux ont permis de confirmer l’importance de l’impact des conditions environnementales sur l’émission des matériaux qui avait été observé dans la littérature. L’étude de ces paramètres environnementaux a été traitée tant dans l’application de modèles présentées dans la littérature que de détermination de facteurs expérimentaux permettant une extrapolation maitrisée de la mesure de l’émission des matériaux à la qualité de l’air dans l’habitacle du véhicule. Enfin, une première méthodologie de modélisation a pu être proposée et appliquée à des systèmes simplifiés permettant de montrer la cohérence de la démarche empruntée. / The thesis is the result of a partnership between the C2MA (IMT Mines Alès) laboratory and Renault, a car manufacturer, as part of a Cifre contract. The awareness of air quality pollution spread among all indoor or outdoor environments. In Asia, strict regulations about vehicle interior air quality have been released to answer this social realisation. The car manufacturers must fulfil these requirements to be able to market their products in these countries (mainly in China). In these circumstances, Renault decided to improve the way they consider the vehicle interior air quality during the design of the vehicles. The thesis work concerns the modelling of vehicle interior air quality because of the technical obligations and the digitalisation. Different research question came up to follow this objective. First of all, the emission of passenger compartment’s materials has been characterised to understand what Volatile Organic Compounds (VOC) are responsible of the degradation of air quality inside a car and what are the sources. Then, a new characterisation approach of emission has been developed allowing to get a better toughness and representativeness of the results. These studies showed the significance of environmental conditions on the emission ofmaterials that had been studied in the scientific literature. The study of the impact of these environmental factors on the material’s emission was the next step and two different research axes has been explored: the study and development of the modelling available in the literature and the establishment of experimental factors leading to a mastered extrapolation of the characterisation of material’s emission to vehicle interior air quality. Finally, a first methodology has been proposed and applied to simplified systems showing the consistency of the developed process.