Recent studies indicate a correlation between high expression of the POZ-ZF transcription factor Kaiso, and the aggressiveness of the triple negative breast cancer (TNBC) subtype. However, little is known about the biological roles of Kaiso in TNBC tumorigenesis and metastasis, which laid the foundation for this thesis. To elucidate Kaiso’s role in TNBC, we generated stable Kaiso depletion in two well-established TNBC cell lines – MDA-MB-231 and Hs578T – using RNA interference technology. Intriguingly, we observed that Kaiso depletion delayed the tumor onset of MDA-MB-231 but not Hs578T cells, and led to the reduced expression of the c-Myc oncoprotein in MDA-MB-231 but not Hs578T cells. We postulate that this reduction in c-Myc expression is partly responsible for the delayed tumor onset observed in MDA-MB-231 cells. Additionally, loss of Kaiso expression resulted in increased apoptosis of both MDA-MB-231 and Hs578T cells in vitro and in vivo, which was accompanied by reduced expression of the DNA repair protein BRCA1. Remarkably, bioinformatic analysis revealed that high Kaiso and BRCA1 mRNA expression correlates with the reduced survival rates of TNBC patients. Further characterization of the Kaiso-depleted cells revealed that loss of Kaiso expression strongly inhibited the metastatic abilities of MDA-MB-231 and Hs578T cells. Importantly, Kaiso depletion led to decreased TGFβ-receptor I and II (TGFβRI and II) expression that is essential for the activation of the TGFβ signaling cascade. Concomitantly, suppressing Kaiso led to reduced TGFβ signaling. As increased TGFβRI expression is independently associated with the poor prognostic outcome of breast tumors, and the TGFβ signaling pathway is highly involved in breast tumor metastasis, we hypothesize that Kaiso functions together with TGFβRI and the TGFβ signaling cascade to promote TNBC metastasis. An additional goal of this thesis was to investigate the role of Kaiso in the prevalence of TNBC in women of African ancestry (WAA) compared to Caucasian women – since increased Kaiso expression is implicated in the poor survival outcomes of breast cancer patients of African ancestry relative to their Caucasian counterparts. Using tissue microarray and immunohistochemical analyses, we revealed for the first time a high nuclear expression of Kaiso in TNBC tissues of WAA (Nigerian, Barbadian, African American) compared to TNBC tissues of Caucasian women. Collectively, these findings unveiled functional oncogenic roles for Kaiso in the tumorigenesis and metastasis of TNBC, and revealed a plausible link between high Kaiso expression, high African ancestry and the predisposition of young WAA to TNBC. / Thesis / Doctor of Philosophy (PhD)

This study investigated the effectiveness of the Triple P Programme to reduce stealing behaviour in three preadolescent children. Using behavioural monitoring and self-report questionnaires, outcome measures included stealing behaviour, parenting practices, parenting efficacy, and parental mental health. A measure of change was also included to identify change points in the therapeutic process. Results suggest that parent training is effective in the reduction of stealing behaviours, as positive changes were found across all the measures employed. This early intervention has the potential to disrupt an antisocial developmental trajectory for children who steal. Limitations of the study and directions for future research are discussed.

No description available.

No description available.

Breast cancer is a complex heterogenous disease that consists of several different subtypes displaying distinct behaviors and responses to different treatments. It is the second leading cause of cancer death among women, and is the most commonly diagnosed cancer in women. Although recent developments have helped shed light into this disease, there is still much to investigate. One particular subtype of breast cancer, known as triple-negative breast cancer, remains the most aggressive, as this tumor type is of high histological grade and preferentially affects women with BRCA1 mutations and women who are younger than 40 years of age. Unlike other subtypes with better prognoses, triple-negative breast cancer still has no targeted therapy, and chemotherapy remains the primary systemic treatment. Recently, there has been an increase of interest in the SOXC family of high mobility group transcription factors and their roles in tumor development. Studies have revealed some of the effects that SOXC genes may have on various tumor types. However, further studies are still needed to elucidate the roles, functions, regulations, and mechanisms of these transcription factors. This study aims to focus on one particular gene in the SOXC family known as sex determining region Y-box 11. Recent studies have shown that sex determining region Y-box 11, also known as SOX11, is one of the factors required for maintaining the basal-like breast cancer phenotype and is also critical in regulating growth, migration, invasion, and expression of signature basal-like breast cancer genes. Emerging evidence also reveals that this transcription factor may have an impact on homologous recombination repair when DNA damage occurs, in triple-negative breast cancer. Using SOX11 overexpression and knockout cell models combined with basic science laboratory techniques and omics, the next generation of laboratory tools, this study seeks to explore the role and function of SOX11 in DNA damage in triple-negative breast cancer. The results of this study have confirmed the recent findings of the role of SOX11 in cell proliferation and growth in triple-negative breast cancer. It has also revealed that overexpression of SOX11 in triple-negative breast cancer cell lines leads to an increase in DNA damage, loss of BRCA1 function, and dysregulation in the cell cycle. High expression of SOX11 is also associated with worse prognostic outcomes in triple-negative breast cancer patients. Because overexpression of SOX11 resulted in a loss of BRCA1 function, there may be a potential role for SOX11 in inducing the BRCAness phenotype commonly seen in basal-like breast cancers. The results of this study strongly suggest that SOX11 is involved in defective DNA damage repair pathways. Further studies need to be conducted in order to evaluate SOX11 as an inducer of the BRCAness phenotype, which occurs when there is a homologous recombination repair defect and no germline BRCA1 mutation present. Because of this, SOX11 may also have the potential to act as a functional biomarker for therapies targeting DNA damage, as recent developments in identifying therapies that could potentially target homologous recombination repair defects have been promising.

The main aim and ultimate final goal of the work carried out in this thesis is a drive towards a feasible system for light harvesting, which is in short, using the Sun’s energy to create electricity or a fuel for our energy requirements here on Earth. This work will see an approach using the triple phase boundary afforded by a microdroplet array. Although light harvesting is an ambition which has seen decades of work and uncountable man-hours, approaching it from the angle of utilizing the triple phase boundary between two immiscible liquids and a solid electrode is a new, and novel concept. Before any attempts towards a light harvesting technique can be made, we will need to have characterized and fully understood the mechanisms and nuances, both for dark and light processes, that are observed at the triple phase boundary. This initial process will start by selection of a suitable redox molecule, and exploring its reactivity in microdroplets under dark conditions. Once this has been achieved, an attempt can be made to use this knowledge, and implement it towards light harvesting. This will eventually include an attempt to couple photo-excited states with other molecules, this will be an important step if energy is ever able to be stored from such a system. This early phase will also see the need to employ many other techniques other than electrochemistry in an effort to aid in the understanding and characterization of the triple phase boundary at microdroplets. This will include travelling to other laboratories in search of specialized scientific skills and apparatus, such as electron paramagnetic resonance, or photocurrent spectroscopy. It will also see the need to build new equipment needed to conduct tests such as surface tension visualization, or new electrochemical cells for photocurrent measurement. In summary, this report will see initial characterization of the processes, both light and dark, that occur within the triple phase boundary of a microdroplet for a given redox molecule dissolved within. Early attempts at coupling excited states with other molecules are also explored. Serendipity has always played a part in scientific discovery and the work outlined in this report was no different. The choice of oil used for the organic phase microdroplet deposits yielded some interesting and unexpected results, and has been implicated as one of the key aspects of the photoreactions that have been explored.

acase@tulane.edu / Study aim: This study aimed to assess the individualized treatment goals (A1C, Blood Pressure, LDL-C) for patients with type 2 diabetes mellitus (T2DM), which lead to optimal health outcomes by different treatment strategies. Background and significance: The evidences in medical guidelines came from clinical trials with highly selected patients, whereas the treatment goals may differ in some subgroups. Additionally, considerable confusions on treatment target has resulted from recent changes in guidelines. So, there is a critical need to examine heterogeneity in optimal goals that lead to the most efficacious treatment options. Methods: A retrospective longitudinal study was conducted for veterans with T2DM by using US Veterans Affairs (VA) Administrative Database (Jan 2005 and Dec 2015). Longitudinal medical records were prepared for each 6-month cycle and multivariate longitudinal regression was used to estimate the risk of microvascular and macrovascular complication events and mortality. Second-degree polynomial and splines were applied in the model to identify the optimal goals in their associations with lowest risk of clinical outcomes by controlling the demographic characteristics, medical history, and medications. Results: 124,651 patients with T2DM were selected, with 62.68 years old (SD=10.96) and 6.72 (SD=6.68) follow-up years at average. In general population, A1C=6.06, LDL-C=106.10 and BP=137.90/98.00 were associated with lowest mortality risk. As of achieving lowest risk of microvascular and macrovascular complication, the optimal goals were A1C=6.81, LDL-C=109.10; and A1C=6.76, LDL-C=111.65, SBP=130.60 respectively. The optimal goals differed between age and racial subgroups. Lower SBP for younger patients and lower LDL-C for blacks were identified with better health outcomes. Conclusions: Individualized treatment goals were identified and multi-faceted treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may improve health outcome in veterans with T2DM. In addition to general ADA recommended goals, health system may examine their own large, more diverse patients with T2DM for better quality of care. / 1 / Qian Shi

<p>Abstract</p><p>The purpose of this study is to reach conclusions that pertain to the key steps involved in the development of a system of innovation. Once identifiable procedures have been reached, then the research seeks to address the characteristics, or roles, that the actors must adhere to in order to keep the system sustainable. When these two areas of research have been concluded, not only will the research question be addressed, but the general applicability of the system of innovation theories will also be challenged in a scientifically relevant way. The main theoretical concepts that will guide the study are Triple Helix, Sustainability, and Innovation.</p><p>The research approach used is deductive, where the information gathered will deem the study as being qualitative. In order to gather the information, six interviews were conducted with various individuals representing actors within the Triple Helix model, and that information was analyzed through interpretism. Due to the social relations occurring in the study, a hermeneutic positioning will derive an underlying positioning in the approach to theory. Once this approach is used, the empirical information gathered from the interviews will be analyzed versus that of the theoretical framework where the conclusions for the study will be generated.</p><p>The practical issue that inspired this study is the Mountain Pine Beetle epidemic occurring in British Columbia, Canada. The timber industry is being decimated due to an increase in the number of beetles, and the result is unusable wood. Because of the resource-reliance in certain milieus that are being effected by the beetle, this study seeks an alternative system for economic stability through a system of innovation.</p><p>The conclusions for the study have very pragmatic characteristics about them. The development of an innovation system begins with the identification of a system leader to mediate the process. The findings suggest that mediation will harmonize the agendas of the actors in the system and work towards a consensus. In addition, contextual issues in the form of knowledge and communication create cultural roadblocks in the implementation process; therefore need to be overcome in order to divert the actors from strict resource dependency. Sustainability in this system involves exclusive responsibilities between the actors involved, but the fundamental challenge rests in routinization of the process. Routinization encompasses micro-level procedures each actor must adhere to, and once this challenge has been overcome, the innovation system will remain sustained.</p>

Abstract The purpose of this study is to reach conclusions that pertain to the key steps involved in the development of a system of innovation. Once identifiable procedures have been reached, then the research seeks to address the characteristics, or roles, that the actors must adhere to in order to keep the system sustainable. When these two areas of research have been concluded, not only will the research question be addressed, but the general applicability of the system of innovation theories will also be challenged in a scientifically relevant way. The main theoretical concepts that will guide the study are Triple Helix, Sustainability, and Innovation. The research approach used is deductive, where the information gathered will deem the study as being qualitative. In order to gather the information, six interviews were conducted with various individuals representing actors within the Triple Helix model, and that information was analyzed through interpretism. Due to the social relations occurring in the study, a hermeneutic positioning will derive an underlying positioning in the approach to theory. Once this approach is used, the empirical information gathered from the interviews will be analyzed versus that of the theoretical framework where the conclusions for the study will be generated. The practical issue that inspired this study is the Mountain Pine Beetle epidemic occurring in British Columbia, Canada. The timber industry is being decimated due to an increase in the number of beetles, and the result is unusable wood. Because of the resource-reliance in certain milieus that are being effected by the beetle, this study seeks an alternative system for economic stability through a system of innovation. The conclusions for the study have very pragmatic characteristics about them. The development of an innovation system begins with the identification of a system leader to mediate the process. The findings suggest that mediation will harmonize the agendas of the actors in the system and work towards a consensus. In addition, contextual issues in the form of knowledge and communication create cultural roadblocks in the implementation process; therefore need to be overcome in order to divert the actors from strict resource dependency. Sustainability in this system involves exclusive responsibilities between the actors involved, but the fundamental challenge rests in routinization of the process. Routinization encompasses micro-level procedures each actor must adhere to, and once this challenge has been overcome, the innovation system will remain sustained.

Uppsatsen bygger på en undersökning om hur tre företag arbetar med CSR. Syftet med undersökningen har varit att granska hur de utvalda företagen väljer att kommunicera dess CSR-arbete till externa intressenter.De frågeställningar studien bygger på är: Hur väljer företag att kommunicera CSR? Kommunicerar företag inom olika branscher CSR på samma sätt? Ser företag inom olika branscher samhällsansvaret på likvärdigt sätt? Finns det någon koppling mellan företags externa kommunikation av CSR och företags medierelation? Under arbetets gång har en respondent från respektive företag intervjuats. En innehållsanalys har även genomförts av företagens hemsidor. Undersökningen har gett författaren kunskap om att de undersökta företagen anser att CSR-arbetet bör finnas utspritt inom hela verksamheten och inte enbart skötas av en person. För att lyckas nå ut till sina externa intressenter på ett effektivt och trovärdigt sätt måste det sociala ansvaret vara en självklarhet för alla inom organisationen och vara en del av företagets vision. Synen på samhällsansvaret skiljde sig mellan företagen vilket kan bero på att det är en tolkningsfråga vad företagen anser är ett socialt samhällsansvar. Dock satte samtliga företag som deltagit i undersökningen in miljöfrågor och sociala frågor i begreppet. De olika företagen som befinner sig i olika branscher arbetar med liknande frågor fast deras tillvägagångssätt och huvudfråga kan skilja sig något mellan branscherna. Hur företagen än väljer att definiera begreppet och hur de än väljer att arbeta med dessa frågor är det en stor fördel att även kommunicera vad de gör till media. Media kan nämligen vara en effektiv kanal för företaget att nå ut till sina intressenter samt att skapa trovärdighet