The aim of the thesis is to develop and verify a test method for the verification of shear compressive strength of wall panels manufactured by Novatop company. Strength verification of adhesive joints in order to perform tests prescribed by the European Technical Assessment in the current company's test room. First, it is necessary to analyse the stress which occurs in the wall of the timber wooden building. Furthermore, it is necessary to design the test methods in such way so that they can be carried out in the company's test room and to introduce the tests in business practice.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24529号 / 医博第4971号 / 新制||医||1065(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 浅野 雅秀, 教授 辻川 明孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>We conducted a study in the virtual environment to explore the influence of three types of lighting (dynamic rim lighting vs. static rim lighting vs. no rim lighting) on users’ visual attention, and the lighting’s potential effects on the users’ preference/choice-making. We recruited 40 participants to complete a virtual grocery shopping task in the experiments, and after the experiment, the participants were given a survey to self-report their experience. We found that (1) the users do not prefer to collect virtual objects with dynamic rim lighting than virtual objects with static rim lighting; (2) the users do not prefer to collect virtual objects with rim lighting than virtual objects without lighting; (3) if the virtual object has a warm-colored texture, it’s more likely to be chosen when it has dynamic rim lighting compared with static rim lighting or no rim lighting; and (4) properties of the dominant color on the texture of a virtual object, such as the B value is a good predictor in predicting if the user tends to choose the object with rim lighting or without rim lighting, while R, B and Lightness values are plausible in predicting if the user tends to choose the virtual objects with dynamic rim lighting or static rim lighting. </p>

No description available.

In virtual worlds, designers often consider "real walking" to be the gold standard when it comes to locomotion, as shown by attempts to incorporate walking techniques within tasks. When real walking is not conceivable due to several different limitations of virtual interactions (space, hardware, tracking, etc.) a walking simulation technique is sometimes used. We call these moderate interaction fidelity techniques and based upon literature, we can speculate that they will often provide an inferior experience if compared to a technique of high or low fidelity. We believe that there is an uncanny valley which is formed if a diagram is created using interaction fidelity and user effectiveness. Finding more points on this graph would help to support claims we have made with our hypothesis. There are several studies done previously in the field of virtual reality, however a vast majority of them considered interaction fidelity as a single construct. We argue that interaction fidelity is more complex involving independent components, with each of those components having an effect of the actual effectiveness of an interface. In addition, the intention of the designer can also have influence on how effective an interface can be. In this study we are going to be doing a deeper look into devices which attempt to overcome the limitations of physical space which we will call semi-natural interfaces. Semi-natural interfaces are sometimes difficult to use at first due to mismatch of cues or possibly due to a lack of fidelity, but training has been shown to be beneficial to overcome this difficulty. As of today, designers have not yet found a fully general solution to walking in large virtual environments. / Master of Science / When a user enters a virtual world, they expect it to be as realistic as possible. They expect to be able to move around an interact with objects exactly how they would in real life. This expectation is, at times, met with dismay when there are limitations between what the user expects to be able to do and what is possible for the experience to achieve. The level of realism in a virtual world is something that we call fidelity, and this comes in different levels ranging from low to high. An interaction in virtual reality which is far from how you would make that same interaction in the real world is called a low fidelity technique and this can be compared to a standard game controller being used to move a character forward. On the other spectrum, a technique in virtual reality with high similarities to the real-world interaction is call high fidelity. An example of a high-fidelity technique would be similar to having a user physically walk from one point to another to move the virtual character. In several studies it has been said that both high fidelity and low fidelity techniques have a positive effect on users and they perform well using them, but if the fidelity of the technique falls in between, it will have a negative effect on user experience. The studies in this document test several different fidelity levels of techniques in an attempt to add evidence to the hypothesis that medium fidelity devices currently do not improve user experience and in fact, are creating a negative one.

Title: Ethical, Social and Political Dimension of Doping in the Field of Sport Objectives: To work up the issue of doping, a brief overview of doping agents and methods, history of doping and antidoping (doping organization, doping control and sanctions). Assess the issue of doping in sport from the perspective of ethical, social and political. Mapping anchoring doping issues in documents or legislation of the Czech Republic and the EU, to reveal the causes and consequences of doping and the prevention and repression as an integral part of the antidoping activities and also to the education of athletes. Methods: The dissertation has a theoretic character, uses qualitative methods: compares, analyse and interprets texts from publications and sources. It draws own conclusions from these bases. Results: This dissertation clears up the issue of doping in the dimensions of ethical, social and political. Collected and interprets virtually all relevant documents, on global scale. Emphasizes the need to combine prevention and repression in the fight against doping and the importance of education in the spirit of sport and the Olympic ideas. Keywords: Antidoping documents - Doping - Ethics in Sport - Evil in Sports - Gamesmanship - Sportsmanship

La fonction de barrière de l'endothélium vasculaire est affectée par des modifications de la cadhérine des cellules endothéliales (VE-cadhérine) telles que la phosphorylation sur tyrosine dans son domaine cytoplasmique et le clivage de son domaine extracellulaire (sVE). Ce travail s'est articulé en deux parties : 1- Etude de ces modifications dans le contexte de la polyarthrite rhumatoïde (PR), et les mécanismes sous-tendus. Ce travail a permis de montrer que la VE-cadhérine est une cible du TNFα, une cytokine essentielle dans la PR, qui induit de la libération de sVE de façon dépendante de l'activité kinase de Src, suggérant l'implication d'un mécanisme de phosphorylation sur tyrosine dans ce processus. De plus, la VE-cadhérine est aussi la cible des protéases de la matrice extracellulaire telles que MMP-2. L'application de ces données fondamentales à la clinique a permis de montrer que sVE était retrouvée dans le sang de patients PR (n=63) et que son taux était corrélé à l'activité de la maladie. Ainsi, le dosage de sVE est d'intérêt dans la prise en charge des patients. 2-Etude de la phosphorylation de la VE-cadhérine dans un contexte d'angiogenèse hormono-régulée au cours du cycle ovarien chez la souris. Les résultats ont montré que le site Y685 de la VE-cadhérine est phosphorylé dans l'ovaire et l'utérus de souris de façon régulée pendant le cycle, ce qui permet de proposer ce modèle physiologique pour étudier la phosphorylation de la VE-cadhérine in vivo. L'analyse de souris knock-in Y685F de la VE-cadhérine (VE-Y685F) a montré que l'absence du site confère une perméabilité accrue dans l'ovaire et l'utérus mais aussi dans les petits capillaires de la peau. De plus, dans deux modèles d'induction d'arthrite, les souris VE-Y685F ont présenté un taux de sVE plus élevé que les contrôles. Au total, sVE et la phosphorylation de la VE-cadhérine ont un vaste champ d'application dans le traitement de la PR ainsi que pour le développement de nouvelles thérapies pouvant s'étendre à d'autres pathologies vasculaires. / The vascular endothelium barrier function is influenced by vascular endothelial cadherin (VE-cadherin) modifications such as its cytoplasmic tail tyrosine phosphorylation and its ecto-domain cleavage (sVE). The work reported herein was divided into two parts: 1- Study of VE-cadherin modifications and the mechanisms underlying these ones in the rheumatoid arthritis context. This work demonstrated that VE-cadherin is a target of TNFα, a highly important cytokine in rheumatoid arthritis (RA) pathogenesis. We found TNFα to induce sVE shedding in a Src kinase dependent manner, suggesting the involvement of phosphorylation mechanism in this process. In addition, this VE-cadherin cleavage requires matrix metalloproteinase activities such as that of MMP-2. Applying these fundamental data to clinical study showed that sVE was detected in sera of 63 RA patients and its titer was correlated with the disease activity. This finding suggests an obvious interest for assaying sVE in RA therapies. 2- Study of VE-cadherin tyrosine phosphorylation in a context of hormones-regulated angiogenesis during mouse estrous cycle. The results showed VE-cadherin phosphorylation at Y685 that was regulated along mouse estrous cycle allowing to proposing mouse estrous cycle as a physiological model for studying VE-cadherin phosphorylation in vivo. The analysis of VE-cadherin Y685F knock-in mice (VE-Y685F) showed that these mice exhibit a higher vascular permeability in uterus and ovaries and the skin small capillaries compared to wild-type animals. Moreover, VE-Y685F mice presented higher levels of soluble VE-cadherin compared to wild-type counterparts in two induced arthritis model. Altogether, sVE and VE-cadherin phosphorylation present an array of interests for RA therapies as well as developing new therapeutic tools in RA and other vascular diseases.

Aujourd’hui, les traitements du cancer colorectal métastatique ont évolué grâce à la combinaison de chimiothérapies conventionnelles à base de 5-FU, oxaliplatine et/ou Irinotécan et de thérapies ciblées dirigées contre le récepteur de l’EGF ou le VEGF. Malgré un taux de survie amélioré par la combinaison de ces drogues, la résistance innée et acquise aux traitements est une cause fréquente d'échec thérapeutique.Dans le but de découvrir de nouvelles cibles thérapeutiques nous avons effectué plusieurs criblages phénotypiques en utilisant des modèles cellulaires de résistance acquises aux chimiothérapies (oxaliplatine et irinotécan) générés au laboratoire ainsi que la lignée HCT116 qui présente une résistance innée aux thérapies anti-EGFR (cétuximab, panitumumab, Erlotinib). Le but final de ce projet étant de révéler des gènes, dont l’inhibition permet de rétablir la sensibilité à l’un de ces traitements, affichant ainsi une interaction létale avec le médicament.Une fois les kinases potentiellement impliquées dans la résistance aux thérapies du CCR identifiées, une inhibition spécifique par shRNA et/ou un inhibiteur spécifique a été effectuée afin de confirmer les potentielles cibles thérapeutiques et/ou biomarqueurs de réponse aux traitements. La cible la plus prometteuse, identifiée comme un déterminant de la résistance à l’oxaliplatine est la protéine ATR (Ataxia-telangiectasia mutated and rad3 related). Une protéine jouant un rôle clé dans la réparation de l'ADN et qui est activée en réponse à la présence d'ADN simple brin persistant (ssDNA) ou de stress réplicatif, pouvant être généré par certaines thérapies anticancéreuses.L’inhibition ATR via son inhibiteur pharmacologique VE-822 (VX-970) combinée à l’oxaliplatine a alors été étudiée par l’utilisation de tests cytotoxiques complétés par une étude d’additivité. Ainsi, nous avons démontré que l’inhibition d’ATR combinée avec l’oxaliplatine entraine une forte synergie dans la lignée HCT116-R1 à la fois en 2D et en 3D. Cet effet est également retrouvé dans d’autres lignées clonales résistantes à l’oxaliplatine (HCT116-R2, SW48-R1) ainsi que dans les lignées cellulaires à l’origine de ces dernières (HCT116, SW48). Nous avons également montré que l'effet synergique de l’oxaliplatine et du VE-822 dans la lignée HCT116-R1 s'accompagne d'une augmentation de la présence d’ADN simple brins suivie de nombreuses cassures double brins de l’ADN, d'un arrêt de la prolifération et d'une induction de l'apoptose. L'apparition de ces dommages à l'ADN est également corrélée avec l'activation de la voie ATM, de p53 et l'inhibition de l'activité CDK2. De plus, in vitro le double traitement provoque une induction des signaux moléculaires à l’origine de la mort immunogène équivalente ou bien supérieure aux traitements par l’oxaliplatine seul. Enfin, l'association d'oxaliplatine + VE-822 est également efficace in vivo, sur des souris immunodéprimées xénogreffées avec les cellules HCT116-R1 ainsi que sur des souris immunologiquement compétentes, avec un effet synergique plus élevé indiquant que la mort immunitaire (ICD) fait partie du mécanisme de cette combinaison de médicaments. En conclusion, toutes ces données confirment l’intérêt du criblage phénotypique dans la découverte de nouvelles cibles thérapeutiques en démontrant pour la première fois le rôle fonctionnel de l'ATR dans la sensibilité à l’oxaliplatine. / Today, treatments for metastatic colorectal cancer have evolved through the combination of conventional chemotherapy 5-FU, oxaliplatin and / or Irinotecan and targeted therapies directed against the EGF receptor or VEGF. Despite an improved survival rate through the combination of these drugs, innate and acquired resistance to treatment is a common cause of therapeutic failure.In order to discover new therapeutic targets we carried out several phenotypic screenings using cellular resistance models acquired to chemotherapies (oxaliplatin and irinotecan) generated in the laboratory as well as the HCT116 line which exhibits an innate resistance to anti-EGFR therapies (cetuximab , panitumumab, Erlotinib). The ultimate goal of this project is to reveal genes, whose inhibition restores sensitivity to one of these treatments, thus displaying a lethal interaction with the drug.Once the kinases potentially involved in resistance to CCR therapies identified, specific inhibition by shRNA and / or a specific inhibitor was performed to confirm the potential therapeutic targets and / or biomarkers for response to treatments. The most promising target, identified as a determinant of resistance to oxaliplatin is the ATR protein (Ataxia-telangiectasia mutated and rad3 related). A protein that plays a key role in DNA repair and is activated in response to the presence of persistent single stranded DNA (ssDNA) or replicative stress, which can be generated by certain anti-cancer therapies.The inhibition of ATR via its pharmacological inhibitor VE-822 (VX-970) combined with oxaliplatin was then studied by the use of cytotoxic tests supplemented by an additivity study. Thus, we demonstrated that the inhibition of ATR combined with oxaliplatin leads to a strong synergy in the HCT116-R1 cell line in both 2D and 3D. This effect is also found in other oxaliplatin resistant clonal lines (HCT116-R2, SW48-R) as well as in the cell lines originating from them (HCT116, SW48).We have also shown that the synergistic effect of oxaliplatin and VE-822 in the HCT116-R1 line is accompanied by an increase in the presence of single-stranded DNA followed by numerous double-stranded DNA breaks, stopping proliferation and inducing apoptosis. The occurrence of this damage to DNA is also correlated with activation of the ATM pathway, p53 and inhibition of CDK2 activity. Moreover, in vitro the double treatment causes an induction of the molecular signals triggering the immunogenic cell death equivalent or superior to the treatments by oxaliplatin alone.Finally, the combination of oxaliplatin + VE-822 is also effective in vivo in immunodeficient mice xenografted with HCT116-R1 cells as well as in immunologically competent mice with a higher synergistic effect indicating that immune death (ICD ) is part of the mechanism of this combination of drugs.In conclusion, all these data confirm the interest of phenotypic screening in the discovery of new therapeutic targets by demonstrating for the first time the functional role of ATR in sensitivity to oxaliplatin.

Kosková, A., Quality of health care services. Diploma thesis, Brno: Mendel University in Brno, 2015. The aim of the diploma thesis is to analyse health care delivery in particular health care organization using quantitative method of questioning the patients and employees of the organization. The theoretical part deals with the basic definitions of quality management in health care, quality of health care, management tools in health care system, measurement of patients and employees satisfaction. Empirical part consists of the evaluation of questionnaires in given health care organization, the identification of critical points and the precaution suggestions. Final results serve as a feedback for management of health care organization.

Theoretical part of this thesis examines the most significant adaptations of Jules Verne´s novels into feature films. From the beginning of cinematography until present days the author describes different artistical approaches during the 20th century around the whole world. The main part of this thesis is an artistic concept of the movie based on Verne´s novel "Ocelové město" (Les Cinq Cents Millions de la Begum). It contains description of the whole idea and author´s proposal for a design introduced in form of paintings based on specific scenes from the novel.