Lung cancer is the leading cause of death in Taiwan cancer patients. The cancer cells are capable of spreading by metastasis and invasion. When tumors spread to distant parts of the body, it is difficult to treat by surgery. In this study, we discovered the novel anti-invasion drugs DMHMPC and DE-DMPC that can inhibit the metastasis and invasion of human lung cancer cell A549. From screening of a chemical library of 420 small molecule compounds using Boyden chamber and MTT assay, the compound DMHMPC and DE-DMPC showed the inhibitory activity toward the invasiveness but not proliferation in human lung cancer cell A549. The results of wound healing assay also showed that DMHMPC and DE-DMPC inhibited the motility of A549 in a dose dependent manner. Moreover, the results of growth curve assay and colony formation assay also showed that DMHMPC and DE-DMPC are not effect proliferation in A549. Together, these results suggested that DMHMPC and DE-DMPC could be the potential drugs to inhibit the invasion of cancer cells that may lead to the new avenue of the cancer prevention therapy.

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Le travail présenté dans cette thèse est le résultat d'une collaboration fructueuse entre la chimie, la physique et la biologie. En effet, des matériaux avec des propriétés physico-chimiques très contrôlées ont été mis à profit dans le but de caractériser des fonctions cellulaires complexes. Nous présentons tout d'abord la création d'un outil permettant l'étude de la mécanotransduction cellulaire. L'originalité de cet outil est basé sur son activation par étirement permettant de lier réversiblement les cellules à la surface. Nous avons ensuite étudié des comportements de cellules souches et cancéreuses en réponse à des microtopographies sous forme de piliers. Cette approche a permis de définir un comportement cancéreux caractérisé par une déformation prononcée des corps et noyaux cellulaires. Nous montrons aussi que l'utilisation de cette surface couverte de micro-piliers permet de décrire la mécano-biologie de cellules cancéreuses. En effet, ce substrat à topographie contrôlée a permis de montrer que la chimie et la rigidité du substrat n'ont que peu d'incidence sur la déformation des cellules cancéreuses, alors que les éléments du cytosquelette sont primordiaux et que sans eux, la déformation n'est pas possible. Nous avons ensuite inhibé une à une des protéines de l'enveloppe et de la lamina nucléaire afin d'évaluer leur implication dans ces mécanismes de déformation. En parallèle, un séquençage total des ARN (Acides RiboNucléiques) de cellules déformées et non déformées a été réalisé dans le but de visualiser d'éventuelles modifications dans l'expression génique. Ces déformations des cellules cancéreuses entre les micro-piliers ont été comparées à celles que subissent les cellules lors de la traversée de membranes poreuses (Chambres de Boyden). Ces comparaisons nous ont permis d'identifier que plusieurs mécanismes peuvent aboutir à la déformation de cellules cancéreuses et en particulier de leurs noyaux. Nous montrons dans une dernière partie que la mitose cellulaire s'effectue sur les surfaces microstructurées. Nous décrivons une ségrégation des chromosomes qui semble être non parallèle. Toutefois, ces divisions atypiques ne causent pas davantage d'accidents mitotiques. / The work shown in this thesis is the outcome of a successful collaboration between chemistry, physics and biology. Indeed, materials with well controlled parameters have been used in order to characterize complex cellular functions. We first introduce the creation of one tool which allow the study of cells mechanotransduction. The originality of this tool is based on its activation by stretching which allow a reversible adhesion of cells to the surface.Then, we studied the behavior of stem cells and cancerous cells on micropillared surfaces. This approach allowed us to describe a cancerous behavior of cells characterized by strong deformations of cells bodies and nuclei. We also showed that the use of such micropillared surfaces allowed us to describe cancerous cells mecanobiology. Indeed, this substrate with a well controlled topography allowed us to show that substrates chemistry and stiffness have only little effects on cancerous cells deformation while cytoskeleton components are necessary. More specifically, the deformation is impossible without the cytoskeleton. We also inhibited the nuclear envelope proteins and nuclear lamina proteins in order to evaluate their involvement in cells deformation mechanism. In the same time, a total RNA (RiboNucleic Acids) sequencing of deformed and non deformed cells have been done in order to identify an eventual modification in gene expression.These deformations of cancerous cells between micropillars have been compared to the deformation of cells during the transmigration through porous membranes (Boyden chambers). These comparisons allowed us to identify several mechanisms which lead to cells deformation and more specifically to nuclei deformation.We showed in a last part that cells can divide on micropillared surfaces. We described a non parallel like segregation of chromosomes. However, these unusual mitosis didn't lead to supernumerary troubles in cell division.

This diploma thesis deals with a leisure time of clients of the Halfway House. The aim of the thesis is to map the content and structure of their leisure time. The thesis seeks to define what the representatives of the target group need for better self realization. Based on these findings author of the thesis design a new program supporting their spending of leisure time. The thesis consists of two parts: theoretical part and practical part. The theoretical part presents a halfway house social service and other programs of the civic association DOM. There are described clients' problems with integration into society. This part of the thesis focuses particularly on the origin of these problems, which mainly come from inadequate care in early childhood and bad family environment or life in an institutonal care later. All psychological and physical needs of a child are not fulfill due to poor care in early childhood and it affects his future mental development. Thesis refers to Pesso Boyden System Psychomotor (PBSP) theory created by Albert Pesso and Diane Boyden - Pesso. PBSP define five basic needs which are necessary for healthy mental development in early childhood. The theoretical part also deals with theory of attachment. Attachment is an emotional bond between child and mother, which has major...

No / The development of therapeutics to treat cancer is conceptually more difficult than for nonlife-threatening diseases for several reasons, including its complex pathophysiological nature, the molecular individuality of each tumor, and the robustness and predictability of preclinical models toward determining efficacy and safety. A major limitation to development of a “blockbuster” therapeutic strategy is the infinite combination of cellular and molecular perturbations and associated heterogeneity of causative genetic factors driving disease progression. Although challenging, the diversity of drug targets, coupled with the lethality of the disease, has encouraged studies of a vast array of approaches and opportunities for disease treatment over the years.

Mgr. Jan Siřínek, The Scenic Principle in Psychotherapy Abstract This dissertation explores the effectivity of a targeted application of body/drama- oriented therapy in the act of inducing a corrective emotional experience. The term scenic- symbolic principle is introduced and meant to 1) ascribe symbolic significance to people, objects, or parts intrinsic to the therapy room; 2) enable these as roles for dramatization; and 3) employ the symbolic significance of physical contact and body motion. Therapeutic schools that use the scenic-symbolic principle are summarized. Detailed attention is given to Pesso Boyden System Psychomotor (PBSP) therapy, in which the scenic-symbolic principle serves as the central instrument in achieving a corrective emotional experience. After examining the theoretical concepts and intervention procedures of PBSP, this paper describes an experiment, in which 40 persons were randomly distributed between experimental and control groups (N = 20 for each group). The goal of the experiment was to achieve a change in attitude towards a job, task, or duty that the subjects were facing, in an effort to reduce negative emotions. While intervention in the experimental group was enriched by using the scenic-symbolic principle, both groups demonstrated significant improvement (pe < 0.001; pc...

Thesis (Ph.D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on April 29, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in English Department of English and Film Studies, University of Alberta. Includes bibliographical references.

Ma thèse est une étude comparée des oeuvres de Joseph Boyden et de Jean Marc Dalpé, et plus spécifiquement de leur imaginaire spatial. Mon analyse se veut essentiellement géocritique et géosymbolique. Elle s’inspire des travaux de Bertrand Westphal, qui s’intéressent à l’insertion et la transformation littéraire des espaces humains. L’ancrage géographique nordique des textes de ces deux auteurs, et plus spécifiquement dans le Nord ontarien où la nature est omniprésente, me semble particulièrement porteur de sens. Il s’agit d’ailleurs de l’élément principal permettant de rassembler et de comparer les oeuvres de Boyden et de Dalpé. Mon étude se centre ainsi sur la géocritique, mais se veut surtout une écocritique, puisque cette approche me permet de cerner davantage les thèmes et les symboles issus spécifiquement de l’environnement naturel. Je procède donc à une exploration du wilderness littéraire dans les oeuvres, qu’il soit forestier, minier, aquatique ou vivant. Grâce aux travaux de William Cronon, je note que ce concept est remis en question dans les oeuvres du corpus, car il ne s’agit pas ici d’un wilderness en tant que nature vierge. Les personnages vivent, au contraire, à proximité de la forêt, entretiennent un contact quotidien avec la nature. Une véritable relation entre les personnages et les éléments de leur environnement se met donc en place. Toutefois, cette relation n’est pas toujours idyllique, car la nature sauvage demeure tout de même dangereuse. Les auteurs puisent parfois dans un symbolisme plutôt universel ou connu, celui des bêtes sauvages dangereuses et des monstres. La forêt boréale est menaçante, et évoque les ouvrages de Robert Progue Harrison ou encore de Margaret Atwood. L’hiver et le froid soutiennent le thème de la survivance. Ma thèse montre aussi que le sentiment d’emprisonnement suscité par la forêt est une symbolique récurrente. Il existe un lien de parenté entre l’univers de la nature sauvage et l’imaginaire de la biorégion du nord ontarien. Cet imaginaire est marqué par des symboles qui cadrent avec l’expérience que font les personnages du wilderness, mais il est aussi teinté par la mythologie autochtone et renvoie ainsi à la présence importante des peuples des Premières Nations dans la région. En somme, mon analyse du symbolisme écologique s’intéresse à la présence d’un wilderness nord ontarien polysémique et multiforme dans les oeuvres à l’étude. En outre, par sa nature comparative, ma thèse montre que malgré les différences de langue, et les différences culturelles qui en découlent irrémédiablement, il y aurait un imaginaire du wilderness commun à ces auteurs canadiens bien connus, imaginaire cependant directement tributaire de la géographie ontarienne.

Mannheimia haemolytica (M. haemolytica)-induced bovine respiratory disease causes millions of dollars in economic losses to Canadian cattle industry. Contemporary management strategies built around the use of antimicrobials are proving to be increasingly unavailing and lead to drug residues in meat which may contribute to the development of multi drug resistant bacteria. Many M. haemolytica vaccines are effective in stimulating antibody responses but studies of vaccina-tion in young calves and the cattle exposed to M. haemolytica (high-risk cattle) have shown poor vaccine efficacy. Antimicrobial peptides (AMPs) may help in the management of respiratory disease caused by M. haemolytica while minimizing the risk of drug residues in animal-derived food products. AMPs are positively charged molecules that can kill bacteria primarily through the electrostatic interactions with the anionic bacterial lipid bilayer. Since the primary target of AMPs is the bac-terial surface charge, which is evolutionarily conserved, the development of resistance towards AMPs seems less likely. These peptides hold potential to replace or reduce the use of antibiotics. Human β-Defensin 3 (HBD3) and Microcin J25 (MccJ25) are cationic peptides that have shown good activity against many Gram-negative bacteria. Five peptides, namely native HBD3, three synthetic HBD3 analogues (28 amino acid, 20AA, and 10AA), and MccJ25 were selected for microbicidal activity against M. haemolytica. Three C-terminal analogues of HBD3 with all cysteines replaced with valines were manually synthesized using solid phase peptide synthesis (SPPS). In all the three analogue, replacement of cysteine with valine rendered them linear and increased their antibacterial activity. Minimum Bactericidal concentration (MBC) assays were performed with the final inoculum size of 1-5x105 cells/ml, with the exception of the 10AA analogue which was incubated with 104 cells/ml final inoculum size. The antimicrobial assay showed that M. haemolytica was intermediately sensitive to HBD3, 28AA and 20AA analogue with an MBC of 50 µg/ml. MccJ25 had limited effect with an MBC greater than 100 µg/ml. The MBC value of 6.3 µg/ml achieved with the 10AA analogue is likely a result of lower final inoculum size. AMPs have several immunomodulatory functions, and these peptides can act as chemoattractant, induce cytokine release that in turn leads to chemotaxis of monocytes and neutrophils. Since neutrophils play an important role in the pathogenesis of BRD, the chemotactic effect of HBD3, 20AA and 28AA peptides on bovine neutrophils was studied using Boyden chamber. Peripheral blood neutrophils isolated from normal healthy cattle showed chemotaxis towards HBD3 and 20AA peptides (P<0.05) but not towards 28AA analogue. Co-incubation of neutrophils with any of the peptides did not affect their chemotaxis towards N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP). Based on these data, it can be concluded that HBD3 and its analogues showed antimicrobial ef-fects against M. haemolytica but MccJ25 had limited microbicidal activity against M. haemolytica. While HBD3 and 20AA analogue were chemotactic for bovine peripheral blood neutrophils, none of the peptides inhibited fMLP-induced migration of neutrophils. These peptides hold potential for further in vivo testing to develop them for use to manage M. haemolytica-induced respiratory disease in cattle.