An experimental study was designed to examine and document the development and structures of turbulent 3D offset jets. The generic 3D wall jets at the same Reynolds numbers was used as the basis of comparison. The experiments were performed using a high resolution particle image velocimetry technique to perform velocity measurements at three Reynolds numbers based on the jet exit diameter and velocities of 5000, 10000 and 20000 and four jet offset height ratios of 0.5, 1.0, 2.0 and 4.0. The measurements were performed in the streamwise/wall-normal plane from 0 to 120 jet exit diameters and in the streamwise/lateral plane from 10 to 80 jet exit diameters. The velocity data were analyzed using (i) mean velocities and one-point statistics such as turbulence intensities, Reynolds stresses, triple velocity products and some terms in the transport equations for the turbulence kinetic energy, (ii) two-point velocity correlations to study how the turbulence quantities are correlated as well as the length scale and angle of inclination of the hairpin-like vortex structures, and (iii) proper orthogonal decomposition to examine the energy distribution and the role of the large scale structures in the turbulence intensities and Reynolds shear stresses. The decay of the maximum mean velocities and spread of the jet half widths became independent of Reynolds number much earlier in the generic wall jet than the offset jets. The flow development is delayed with increasing offset heights. The decay rate and wall-normal spread rate increased with the offset heights, whereas the lateral spread rate decreased with offset heights, which is consistent with previous studies. The two-point auto-correlations and the proper orthogonal decomposition results indicate the presence of more large scale structures in the outer and self-similar regions than in the inner and developing regions. The iso-contours of the streamwise autocorrelations in the inner regions were inclined at similar angles of β = 11.2 ± 0.6 degrees, which are in good agreement with reported values in boundary layer studies. The angles decrease with increasing distance from the wall.

Regulatorische CD4+CD25+ T-Zellen (Tregs) stellen eine kleine Zellpopulation dar (1-5% der peripheren Blutzellen), die hauptsächlich für die Regulierung von Immunreaktionen verantwortlich ist. In der vorliegenden Arbeit wurden diese Zellen gemeinsam mit Stammzellen syngen und allogen kotransplantiert, um ihren Effekt auf das Anwachsen der Spenderzellen und die Rekonstitution der Hämatopoese nach Ganzkörperbestrahlung zu untersuchen. Es wurden humanisierte dreifach transgene Empfängermäuse (C57Bl/6-TTG) verwendet (human CD4+, murin CD4-, human HLA-DR+), wodurch sowohl bei syngener als auch bei allogener Transplantation eine Unterscheidung zwischen Spender- und Empfängerzellen möglich ist. Zunächst wurden CD4+CD25+ T-Zellen durch Separation aus Milzzellen bzw. Buffy Coats gewonnen und in vitro mittels Durchflusszytometrie und ELISpot charakterisiert. Anschließend fanden syngene und allogene Transplantationen mit einer Laufzeit von 61 Tagen statt. Überleben und Gewicht wurden täglich ermittelt und außerdem wurden wöchentlich Blutbilder erstellt und durchflusszytometrische Chimärismusanalysen (murines und humanes CD4, CD8, MHC (H2Db, H2Kd)) durchgeführt. Durch die magnetische Separation konnte die FoxP3-Expression der murinen Zellen (Transplantat) von 1,6% in der Ausgangspopulation auf 68,5% in der CD4+CD25+ Population gesteigert werden. In den ELISpot-Assays zeigten diese separierten Zellen, wie für Tregs typisch, keine Produktion von Interleukin-2. Nach syngener Transplantation (Spender: wildtyp C57Bl/6) von 2x106 Knochenmarkzellen und 1x106 CD4+CD25+ T-Zellen überlebten 100% der Tiere, wie zu erwarten war. Dabei setzte bei Tregs-kotransplantierten Tieren die Blutbildung nach bestrahlungsbedingter Leukozytopenie aufgrund bisher nicht bekannter Mechanismen früher wieder ein und der Donor-Zell-Chimärismus war an Tag 19 nach Transplantation signifikant höher als in der Kontrollgruppe. Dies zeigt, dass regulatorische T-Zellen im syngenen Transplantationsmodell einen positiven Effekt auf die Akzeptanz bzw. das Anwachsen des Transplantats haben. Dieses Modell entspricht klinisch einer autologen Transplantation. Nach einer knochenmarkzerstörenden Therapie werden dem Patienten eigene Stammzellen reinfundiert, um die Blutbildung und das Immunsystem wieder in Gang zu bringen. Der Zusatz von regulatorischen T-Zellen zum autologen Stammzelltransplantat könnte das Anwachsen der Zellen beschleunigen und die gefährliche Phase der Immunsuppression, in der es häufig zu Sekundärinfektionen kommt, verkürzen. Die Transplantation der gleichen Zahl von allogenen Spenderzellen (wildtyp Balb/c) führte überraschend zum Tod aller dreifach transgenen Empfängertiere. Der Vergleich zu Experimenten mit wildtyp C57Bl/6-Empfängertieren zeigte, dass dreifach transgene Mäuse sehr viel höhere Zellzahlen im Transplantat zum Überleben benötigen (Daten nicht gezeigt). Das Ausbleiben der Blutbildung nach der Bestrahlung führte zu vermindertem Allgemeinbefinden, gestörter Futter- und Wassseraufnahme und Exsikkose bis zum Tod bzw. aus Tierschutzgründen zur Euthanasie. Durch Erhöhung der Zellzahl im Transplantat auf 1x107 Knochenmark + 5x106 Milzzellen überlebten 25% der Mäuse, bei 3x107 Knochenmark + 5x106 Milzzellen waren es 50%. Anders als im syngenen Modell führte die Kotransplantation 1,5x106 allogener CD4+CD25+ T-Zellen zu 3x107 Knochenmark + 5x106 Milzzellen zum Versterben der Tiere. Dies verdeutlicht, dass regulatorische T-Zellen in diesem allogenen Transplantationsmodell das Anwachsen des Transplantats behindern (Transplantatversagen). Hier gilt es zu klären, ob dieser Effekt spezifisch für die gewählten Mausstämme ist und welche Mechanismen für das Transplantatversagen verantwortlich sind. In einem dreifach transgenen Mausmodell konnte ein positiver Effekt von regulatorischen T-Zellen auf die Rekonstitution der Hämatopoese bei syngener Kotransplantation nachgewiesen werden. Im allogenen Transplantationsmodell hingegen führte die Kotransplantation CD4+CD25+ T-Zellen zum Versterben der Empfänger. Der beschriebene und schon publizierte positive Effekt spenderspezifischer Tregs zur Behandlung von Graft versus Host Disease nach allogener Stammzelltransplantation widerspricht diesen Ergebnissen nicht, da es bei diesen Patienten schon zum Engraftment von hämatopoetischen Stammzellen gekommen ist. Dies hat weitreichende Konsequenzen für die therapeutische Anwendung regulatorischer T-Zellen bei hämatologischen Erkrankungen in der Human- und Veterinärmedizin. / Regulatory CD4+CD25+ T cells (Tregs) represent a small cell population (1-5% of peripheral blood cells) mainly responsible for the regulation of the immune system. In the present work, these cells were cotransplanted with syngeneic and allogeneic stem cells in order to analyze the effect of Tregs on the reconstitution of hematopoiesis after total body irradiation. Humanized triple transgenic hosts (C57Bl/6-TTG) (human CD4+, murine CD4-, human HLA-DR+) were applied allowing differentiation of donor and host cells in syngeneic and allogeneic transplantation settings. Murine and human CD4+CD25+ T cells were magnetically separated out of splenocytes or buffy-coats and characterized in vitro by means of flow cytometry and ELISpot. Afterwards syngeneic and allogeneic transplantation experiments were performed for a period of 61 days. Survival and weight were assessed daily and once a week blood parameters and chimerism analyses (murine and human CD4, CD8, MHC (H2Db/ H2Kd)) were carried out. FoxP3 expression increased from 1,6% in the initial murine cell fraction to 68,5% in the separated CD4+CD25+ T cells. ELISpot assays showed the typical lack of interleukin 2 production of Tregs. After syngeneic transplantation (donor: wildtype C57Bl/6) of 2x106 bone marrow cells and 1x106 CD4+CD25+ T cells, 100% of mice survived what was to be expected. Cotransplanted animals showed earlier reconstitution of hematopoiesis after leukocytopenia and significant higher donor-cell-chimerism on day 19 after transplantation. The mechanisms for this positive effect of Tregs in syngeneic transplantation on the engraftment have to be investigated. This model clinically correspond an autologous transplantation where patients are treated with their own stem cells after a myeloablative treatment (chemotherapy or irradiation). The addition of regulatory T cells to the transplant could accelerate the engraftment and shorten the risky period of immunosuppression. Injection of the same numbers of allogeneic cells (donor: wildtype Balb/c) did not preserve hosts from mortality. Compared to experiments with wildtype recipients, results showed that triple transgenic mice need much higher cell numbers in the transplant for survival (data not shown). The failure of hematopoiesis after irradiation led to reduced general condition, disordered ingestion and exsikkosis leading to death respectively to euthanasia for reasons of protection of animals. By scaling up the cell number in the inoculum to 1x107 bone marrow cells + 5x106 splenocytes 25% of mice survived, with 3x107 bone marrow cells + 5x106 splenocytes survival was 50%. In contrast to syngeneic experiments, cotransplantation of 1,5x106 allogeneic CD4+CD25+ T cells and 3x107 bone marrow cells + 5x106 splenocytes did not prevent animals from mortality. In this allogeneic transplantation model Tregs restrain engraftment (graft failure). It has to be clarified if this effect is specific for the utilized mouse strains and which mechanisms are responsible for the graft failure. In the syngeneic triple transgenic mouse model cotransplantation of CD4+CD25+ T cells showed a positive effect on reconstitution of hematopoiesis after irradiation. In the allogeneic setting however cotransplantation of allogeneic regulatory T cells avoided the engraftment of transplanted cells. The described and published effect of donor-specific Tregs for treatment of graft versus host disease after allogeneic transplantation does not contradict the presented results because treated patients already possessed engrafted hematopoietic stem cells. The results have wide consequences for the therapeutic appliance of regulatory T cells in hematological diseases in human and veterinary medicine.

Alternative fuel types and technologies are increasingly being advocated for transportation needs to ameliorate concerns around energy security, climate change, and fuel cost. Each fuel type has unique advantages and disadvantages for cost structure and emissions. Meanwhile, corporate fleet customers are often making more sustainable choices of vehicle type due to public perception and other influencing factors. The sustainability of these vehicles can be viewed from a triple bottom line perspective of financial, environmental, and societal implications. However, there is currently a lack of organized knowledge that would allow a decision-maker to elect the appropriate vehicle type beyond lifecycle cost and carbon emissions. The simplification of the impact of fuel type choice disregards issues that are emerging in prominence around water consumption and public health. Water consumption is of particular importance to investigate as fuel types that have reduced carbon emissions are often more water intensive. This thesis develops a tool that examines these issues through modeling to provide a more holistic lifecycle view of a prospective fleet's impact. The choice of vehicle type then can be optimized by utility theory preference elicitation of the different customer desires. Various scenarios of corporate preference and fleet specifications are explored to provide case studies that exemplify the complexity of the decision process. Each potential scenario has its own characteristics that cannot be optimally fulfilled by an overarching fuel type but rather should be thoroughly examined individually to understand the true consequences.

Abstract The primary focus of this research project was an evaluation of the Group Stepping Stones Triple P parenting program for parents of a child with a disability. In addition there was an investigation into the similarities and differences in child behaviour and parenting experience, and program outcomes, for families of children with different developmental disabilities. While the Triple P Positive Parenting Program has an impressive evidence base (Sanders, 1999; Sanders, Markie-Dadds, Tully & Bor, 2000) and research indicates that the standard Stepping Stones Triple P Program is efficacious for different disability groups (Roberts, Mazzucchelli, Studman & Sanders, 2006) and for parents of children with Autistic Spectrum Disorders (Whittingham, Sofronoff, Sheffield & Sanders, 2009), to date the group version of Stepping Stones Triple P has not been comprehensively evaluated, nor the efficacy of the program evaluated when administered concurrently to parents of children with different developmental disabilities. Currently, there is a lack of participant-friendly, evidence-based group parenting programs that can be utilised in a cost-effective manner with all parents of children with disabilities. Many interventions have been designed specifically to cater to the requirements of a particular disability group. While there is some divergence in disability characteristics and in the experience of families of children with different disabilities, there is compelling evidence that many of the most challenging experiences faced by parents of disabled children (such as emotional and behavioural disturbance and delays in skill development) are shared by many disability populations (Raina et al., 2005; Bourke et al., 2008). Consequently there is empirical support for the implementation of a broad, skill-based parenting program for all parents of children with disabilities. The first study in this research project was a randomised controlled trial the Group Stepping Stones Triple P program for parents of children with Autism Spectrum Disorders (ASD), Down syndrome, other intellectual disabilities and Cerebral Palsy. Fifty-two families were included in this trial and were randomly allocated to treatment and wait-list control groups. The results demonstrate significant improvements in child behaviour and parenting difficulties that were maintained at follow-up six months later. For over a third of participants the change in child behaviour and parenting styles was clinically reliable (Jacobsen & Truax, 1991; Evans, Margison & Barkham, 1998). In addition, the majority of parents reported the attainment of their program goals following the intervention. The second study was a comparison of program outcomes for parents from different disability groups. The sample was divided into two groups; parents of children with ASD and parents of children with intellectual and physical disabilities. The results demonstrated significant improvements in child behaviour and parenting difficulties from pre- to post-intervention for both the ASD group and the Intellectual and Physical disability group. For a third of parents in the ASD group and over a third of parents in the Intellectual and Physical disability group, the changes were clinically reliable (Jacobsen & Truax, 1991; Evans et al., 1998). In addition, the means for both groups on the child behaviour, parenting style and parental psychological functioning variables were compared. The results indicated that there were some differences in child behaviour, parenting styles and parent distress between the two groups, and in the program goals set by parents. However, overall the results revealed no systematic differences in treatment outcomes across disability groups, demonstrating that the program was effective for families of children with ASD and families of children with Intellectual and Physical disabilities. Finally, a series of three case evaluations were conducted to examine program outcomes and differences in child behaviour and parenting experiences for the families of a child with ASD, Down syndrome and Cerebral palsy. The results of the case studies revealed significant improvements in child behaviour and parenting styles for all three families, along with high levels of program satisfaction and successful attainment of parenting goals. For all three families these changes in child behaviour and parenting style were clinically reliable (Jacobsen & Truax, 1991; Evans et al., 1998) and maintained at six-month follow up. The results also provided information about the similarities and differences in parenting experiences, child behaviour and program goals across the three disabilities. Overall, this research project has demonstrated that the Group Stepping Stones Triple P program is an effective parenting intervention for challenging behaviour and dysfunctional parenting in families of children with a range of developmental disabilities. The results of this research provide evidence to suggest that mixed disability group format used in the administration of the Group Stepping Stones Triple P program did not preclude positive program outcomes. Finally, the results of this research project indicate that there are many shared parenting experiencing across families of children with different disabilities and that regardless of observed differences in disability characteristics and family experiences, the Group Stepping Stones Triple P program is sufficiently flexible and comprehensive in its scope to meet the needs of families from different disability populations.

Syfte: Denna studie syftar till att kartlägga i vilken utsträckning företag på en svensk marknad arbetar med CSR och även att identifiera ett eventuellt samband mellan hållbarhetsarbetets utsträckning och lönsamhet i form av EPS och DuPont. Dessa lönsamhetsmått representerar dels ett investeringsperspektiv, dels ett internt företagsperspektiv. Metod: En kvantitativ studie har gjorts på Stockholmsbörsens Large Cap med en indelning av företagen på en hållbarhetsskala. Datan har analyseratstillsammans med lönsamhetsmåtten EPS och DuPont genomkorstabulering samt en statistisk analys. Slutsats: Denna studie finner att det finns ett engagemang för CSR inom LargeCap och det finns ett negativt samband mellan CSR-arbete och EPS.Studien finner inget samband mellan CSR-arbete och DuPont. Det finns en obalans i prioriteringen av TBL där det ekonomiska perspektivet är det främsta.

Philosophiae Doctor - PhD (School of Business and Finance) / As organizations face stiff pressure from various stakeholders, management has had to move beyond the idea of shareholder wealth maximization and incorporate the environmental and social concerns from the various stakeholders. The study identifies how Sustainable Supply Chain Management (SSCM) practices enable the firm to manage the social, environmental and economic Triple Bottom Line (TBL) for four key stakeholder groups - customers, suppliers, regulators and the community. The study adopted a case study design, focused on Safaricom, arguably Africa's most innovative cellular firm which has championed the M-pesa money transfer platform. The objectives were, first, to establish key attributes namely; power, legitimacy and urgency of selected stakeholders of Safaricom and the key determinants of their salience, second, to determine stakeholder expectations and how they hold Safaricom accountable; third, to identify the extent of Safaricom's influence and control over the selected stakeholders; and finally, to establish how and to what extent the firm manages stakeholder exposure through their SSCM practices and TBL measures. Data from semi-structured interviews with Safaricom management and the four key selected stakeholder groups, together with company and public documents, were analyzed using qualitative content analysis. Stakeholder groups were selected to represent examples of low, moderate or high levels of salience and exposure. While all are considered important, the case reveals how Safaricom management prioritizes and addresses stakeholder needs according to their attributes. As each stakeholder group is heterogeneous, the case reveals how the firm manages each distinctively and adopts diverse SSCM practices, which are aligned with the firm's TBL measures. Moreover, stakeholder exposure has a moderating effect on the relationship between the firm's SSCM practices and the TBL measures.

A carcinicultura potiguar está sob forte pressão das organizações governamentais e principalmente não governamentais, que associam a destruição de ambientes naturais à expansão das áreas de produção de camarão. Este trabalho visa caracterizar e avaliar o setor de carcinicultura no Rio Grande do Norte, identificando a dinâmica econômica, social e ambiental do setor, a partir da análise da conduta econômica, social e ambiental, frente às pressões da estrutura de mercado em que operam. Para isso, utiliza o modelo ECP-Triplo de estrutura, conduta e performance, onde as empresas submetidas a pressões econômicas, sociais e ambientais em sua estrutura industrial adotam uma conduta econômica, social e ambiental para obter resultados também tríplices na performance econômica, ambiental e social. Foi realizada uma pesquisa quali-quantitativa, por meio da aplicação de um questionário estruturado e entrevistas. O questionário foi aplicado em 21 empresas nas zonas homogêneas das regiões Agreste, Mossoroense, Litoral Norte e Litoral Oriental do estado do Rio Grande do Norte. A pesquisa coletou dados junto a proprietários, diretores, gerentes e responsáveis por unidades de laboratório de pós-larva, fazendas de engorda e processamento / beneficiamento que compõem os principais elos da cadeia produtiva do camarão cultivado. A análise dos resultados demonstra que a indústria de cultivo de camarões no Rio Grande do Norte apresenta a maior produção no Brasil, porém, ainda falta a aplicação de condutas econômicas, sociais e ambientais adequadas para suportar as pressões da estrutura da indústria. Conclui-se que a descapitalização do setor, a demora na concessão das licenças necessárias para a implantação e ampliação das fazendas, a falta de incentivos governamentais, a pressão por parte das organizações não governamentais, a falta de ambiente cooperativo entre as empresas, a ausência de políticas públicas de incentivo à produção, os juros altos e a elevada carga tributária são alguns dos fatores que vêm prejudicando o desenvolvimento da carcinicultura no estado do Rio Grande do Norte. As instituições de pesquisa, juntamente com a Associação Brasileira de Criadores de Camarão (ABCC) e os governos federal, estadual e municipal precisam definir uma forma de exploração sustentável do ecossistema manguezal e elaborar políticas ambientais específicas para a carcinicultura. Enfim, é necessária, a implantação e utilização de uma conduta ambiental e socialmente responsável como estratégia para que a carcinicultura potiguar alcance níveis de excelência e prosperidade, mantendo uma vantagem competitiva permanente. / The shrimp aquaculture produced from Rio Grande do Norte have been under pressure by governmental and non-governmental organizations, which associate the natural environment destruction to the expansion of shrimps’productive areas. This work aims to characterizer and evaluate the aquaculture shrimp sector in Rio Grande do Norte, identifying the economic, social and environmental dynamic of this sector, based on the analysis of the economic, social and environmental conduct, front to the pressures of the market’s structure in which it operates. To do this analysis, this work used the Triple-SCP model of structure, conduct and performance, in which companies under economic, environmental and social pressure in its industrial structure follow an economic, environmental and social conducts to obtain triple results in the economic, environmental and social performance. In this research a qualitative and quantitative methodologies have been done and it applied structural questionnaires and did some interviews. The questionnaire was applied to 21 companies in homogeneous zones from the region of Agreste, Mossoroense, Litoral Norte and Litoral Oriental from Rio Grande do Norte State. The corpus was collected and the participants were owners, directors and managers responsible for the worm laboratory, fattening farming and processing which set the link of the preserved shrimp productive chain. The analysis shows that the shrimp aquaculture industry in Rio Grande do Norte has the major production in Brazil, however, it’s missing the adequated application of economic, social and environmental conducts to support the structure of the industry’s pressure. To conclude, we suggest that the sector’s descapitalization, the licenses’delay necessary to the farming implementation and expansion, the missing of governmental incentive and the pressure of non-governmental organizations, the missing of cooperative environment among companies, and the absence of public politics to motivate the production, the high interest and raised tributive are some of the reasons that have damaged the development of shrimp aquaculture in the Rio Grande do Norte State. Researches Institutions as well as Brazilian Shrimp Farmers Association (ABCC) and the Federal, State and Municipal Governments should define a way for a sustainable exploration of the mangrove systems and elaborate a specific environmental politic to shrimp aquaculture. It´s necessary to implement the environmental utilization and social conducts as strategies to the shrimp aquaculture in the Rio Grande do Norte to reach levels of excellence and prosperity, as well as to sustain a permanent competitive advantage.

Dans cette thèse, nous souhaitons décrire la dynamique du front d'avancement d'un film mince s'écoulant sur un plan incliné non rugueux. Nous nous intéressons surtout au problème de point triple situé à l'interface entre la paroi solide, le fluide en mouvement et l'air, par exemple lors de l'écoulement d'une goutte sur une surface inclinée. Dans une première partie, nous expliquons pourquoi on peut se ramener aux équations de Stokes et pourquoi le problème résultant est mal posé. Pour y remédier, la condition de non-glissement à la paroi est remplacée par une condition de glissement lorsqu'on est proche du front. Ainsi on réussit à trouver une solution dans H1. Puis nous développons la dynamique de l'écoulement à l'amont du front : un film mince. Cet écoulement peut se modéliser sous la forme d'équations de type Saint-Venant sur la hauteur et le débit. Nous justifions cette construction à partir des équations de Navier-Stokes en utilisant un développement asymptotique en fonction du paramètre onde longue. Dans la zone du front nous résolvons le système de Stokes stationnaire avec glissement au fond par un développement asymptotique en fonction du nombre capillaire. Le front est divisé en une zone interne près du front et une zone externe loin du front, puis les solutions de chaque zone sont soit raccordées directement (angles dynamique et statique égaux), soit raccordées au moyen d'une zone intermédiaire (angles dynamique et statique différents). Cela nous conduit à deux familles de modèles. En réunissant les modèles type Saint-Venant et les différents modèles de front, nous obtenons un modèle de Saint-Venant tenant compte de la dynamique du front. À partir de ce modèle à deux équations nous pouvons écrire un modèle plus simple à une équation sur la hauteur. Ce modèle permet d'étendre les modèles existants avec adhérence à des modèles avec glissement. On peut alors réaliser des simulations numériques combinant un front d'avancement et un film mince / In the present work, we describe the dynamics of a moving contact line for thin films flowing down an inclined plane. Our focus is the problem of triple point located at the interface between the solid wall, the moving fluid and air, for example the spreading of a drop on a plane dry wall (horizontal or inclined) due to gravity and capillarity. In the first part, we explain how we can reduce to the Stokes equations and why the resulting problem is ill-posed. This singularity is removed by permitting the fluid to slip along the wall close to the contact line. Thus we manage to find a solution in H1 constructed by asymptotic expansions. Then we focus on the upstream dynamic of the flow, which is set to a thin film flow. We develop the classical system of Shallow-water equations (Saint-Venant equations) from the full Navier-Stokes system using the classical long-wavelength expansion. We obtain a set coupled equations for the flow depth and the flow-rate. In the neightboorhood of the contact line, we develop an asymptotic expansion of the steady Stokes system with slip at bottom in function of the capillary number. The solution in the vicinity of the contact line is developped in the inner region and the outer region. Then, a direct matching can be done (assuming dynamic and static angles are equals) or using an intermediate region (with different angles). This leads to two different families of models. Bringing together the upstream Shallow-water equations and the contact line models, we write a new Shallow-water model taking into account the dynamic of the moving contact line. Then, we deduce a simplier one-equation model for the film thickness. This model extends existing models with no slip at bottom to models with slip. Direct numerical simulations of the last models are performed, combining a moving contact line and a thin liquid film

Made available in DSpace on 2016-12-23T13:49:03Z (GMT). No. of bitstreams: 1 Isabella dos Santos Guimaraes.pdf: 1486152 bytes, checksum: 65f12f2a8d639d0b762766b845fea774 (MD5) Previous issue date: 2013-04-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Triple-negative breast cancer (TNBC) is a heterogeneous and poor prognostic disease, partially due to its ineligibility to target therapy, and the high relapse index, despite the initial satisfactory response to antineoplastic drugs. Therefore, the identification of alternative substances is urgent, as herein presented with regard to metformina and TNBC (lineage MDAMB231). Despite the low percentage of apoptotic/necrotic cells induced by metformin, 4.1% (10 μM) e 8.8% (54 mM), there was a discrete increase of cells in sub-G0, which is in agreement with the low value, despite doubled, of apoptosis/necrosis induced by metformina 54 mM. Metformin reverted ERK constitutive activation, possible antineoplastic mechanism; however, only reduced cellular proliferation at high doses (10 μM vs. 54 mM, 9.8% vs. 45.23%, respectively), possibly due to the modulation of other mechanisms of action. Paclitaxel 0.25 μM induced apoptosis/necrosis in 29% of the cells, which is comparable to the 36.34% of dead cells obtained by MTT. Despite the cell cycle arrest in G2/M that favours its mechanism of action, its antineoplastic efficacy can be compromised by ERK constitutive activation, which is related to taxane chemoresistance. Metformin 10 μM combined with paclitaxel 0,25 μM, although synergic with regard to the antineoplastic effect (dead cells = 53.20%), kept constant the induction of apoptosis/necrosis when compared to paclitaxel alone, as the benefit of arresting the cell cycle at G2/M can be overcome by ERK constitutive activation. When administered at their IC50, metformin 54 mM and paclitaxel 0,25 μM, the percentage of apoptotic/necrotic cells increased to 41%, which is comparable to the decrease in cell proliferation (59.9% of dead cells). Worthwhile pointing that: i) ERK constitutive activation was reversed, favoring paclitaxel toxicity; ii) the number of cells in sub-G0 increased. Indeed, among the 41% apoptotic/necrotic cells, 21.4% derived from late apoptosis, thus justifying sub-G0 expansion. The data point to mutual synergism between metformina and paclitaxel. Our findings support that, among other mechanisms of action, metformina is an indirect inhibitor of ERK, possibly of mTOR as well, explaining, therefore, its potential application in the treatment of TNBC, a major challenge of clinical oncology / O câncer de mama triplo-negativo (TNBC) configura doença heterogênea e de prognóstico ruim, dentre outras razões, por não ser responsivo às terapias-alvo e pelo elevado índice de relapso da doença apesar da responsividade inicial satisfatória aos antineoplásicos. Sendo assim, há urgência na identificação de substâncias alternativas, como ora apresentado em relação à metformina e TNBC (linhagem MDAMB231). Embora a porcentagem total de células em apoptose/necrose induzida por metformina seja pequena, 4,1% (10 μM) e 8,8% (54 mM), houve aumento discreto de células na fase sub-G0; aspecto concordante com o valor baixo, ainda que dobrado, de indução apoptose/necrose por metformina 54 mM. Metformina reverteu a ativação constitutiva de ERK, possível mecanismo antineoplásico da droga, mas somente reduziu a proliferação celular em doses elevadas (10 μM vs. 54 mM, 9,8% vs. 45,23%, respectivamente), possivelmente pela modulação de outros mecanismos de ação. Paclitaxel 0,25 μM promoveu apoptose/necrose em 29% das células, valor compatível os 36,34% de células mortas por MTT. Apesar da parada do ciclo celular em G2/M, favorecendo seu mecanismo de ação, sua eficácia antineoplásica limitada pode decorrer da sustentação da ativação constitutiva de ERK, já relacionada à quimiorresistência ao taxano. A combinação de metformina 10 μM com paclitaxel 0,25 μM, embora seja sinérgica quanto à ação antineoplásica (células mortas = 53,20%), manteve constante a indução de apoptose/necrose quando comparado ao paclitaxel sozinho, já que o benefício do aumento de células em G2/M pode ter sido sobreposto pela ativação de ERK. Quando administradas em suas IC50, metformina 54 mM e paclitaxel 0,25 μM, o percentual total de células apoptóticas/necróticas aumentou para 41%, valor mais próximo àquele de diminuição da proliferação celular (59,9% de células mortas). É notório ter havido: i) reversão da ativação constitutiva de ERK, favorecendo a citotoxicidade de paclitaxel; ii) aumento de células em sub-G0. De fato, dos 41% de células em apoptose/necrose, 21,4% derivaram de efeito apoptótico tardio, justificando a expansão de sub-G0. Os dados apontam para sinergismo mútuo entre metformina e paclitaxel. Nossos achados evidenciam que, dentre outros possíveis mecanismos, a metformina atua como inibidor indireto de ERK, possivelmente também de mTOR, explicando, portanto, seu uso potencial no tratamento do TNBC, um dos grandes desafios da clínica oncológica

This diploma thesis deals with the topic of social business in the South Bohemian and Pilsen Region, its development and possibilities for further development. The aim of the thesis is to evaluate the state of social business in both regions and to recommend possible steps that would lead to a greater development of social business in the Czech Republic. The theoretical part deals with the history of the social economy and its subjects. Attention is also devoted to social entrepreneurship, its development and the principles that social enterprises must follow. Further, there is described the development of social entrepreneurship in the Czech Republic, legislation and support possibilities for social enterprises. In this section, there are also examples of countries where social enterprises is working successfully. These are Great Britain, Italy and Poland. The practical part deals with the evaluation of the questionnaire survey, which took place among managers of social enterprises in both regions. Questions in the questionnaire were very broad. There were questions about the size of the enterprises , the cooperation, the problems that enterprises face or the benefits of doing business for the company. Based on the results of this survey, research questions were answered. Further, recommendations are described in this part, which could help to further develop social entrepreneurship in the Czech Republic. This is rather a nationwide recommendation. In this case, the empirical investigation is rather supplementary.