This study examined the dynamics, challenges and opportunities of developing innovation systems in low resource settings with a particular focus on Uganda. It applied perspectives of technoscience and concepts of innovation systems, triple helix as university-industry-government relationships, mode 2 knowledge production and situated knowledges in understanding the context, identifying key policy issues and suggesting ways to address them. A mixed methodology combining both quantitative and qualitative methods was used in the study. It involved review of key policy documents, key informant interviews, focus group discussions and meetings with scientists, business leaders in the target organizations and firms, community members as well as observations of production processes in firms. Findings underscore the need for greater interaction and learning among actors in the emerging innovation systems in Uganda and eastern Africa. An opportunity for this to happen may be the growing number of entrepreneurial initiatives at the university and some public research organizations in the country. These entrepreneurial initiatives are driven by scientists, who are enthusiastic about moving their research results and innovations to market. This makes it plausible, in low resource settings like in Uganda, to promote the university working closely with public research organizations and firms as a locus for research and innovation. However, enabling conditions, which foster interaction and learning among actors, should be put in place. First, there is need to formulate specific policies and strategies with clear goals and incentives to promote growth of particular innovation systems. Second, a clear national policy for financing research and innovation is needed, which involves on the one part core funding to universities and research organizations, and on the other, competitive grants for research and innovation. Third, business incubation services should be established and/or supported as places where entrepreneurial scientists and other persons develop and test their business ideas and models. Fourth, there is need for institutional reforms to make administrative processes less bureaucratic, more costeffective and efficient. These reforms are necessary for example in processes involving procurement and financial management, research project approvals (for ethics and safety), technology assessments, contracting and licensing and other registration services. The findings and conclusions from this study demonstrate that technoscientific perspectives and innovation systems approaches can be adapted and used as a framework for identifying and explaining conditions that promote or hamper innovation in low resource settings as well as policy options to address them.

<p>Breast cancers with a basal-like gene signature are primarily triple-negative, are frequently metastatic, and carry the worst prognosis. Basal-like breast cancers are frequently enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT). While EMT is generally thought to be important in the process of metastasis, direct in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triple-negative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence of epithelial-mesenchymal plasticity in the patient.</p><p>In culture, the DKAT cell line exhibits a basal epithelial phenotype under normal culture conditions in serum-free MEGM, and can undergo a reversible EMT in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. Additionally, we find that expression of the cytokine IL-6 is dramatically increased in mesenchymal DAKT cells, and blocking IL-6 signaling reduces expression of Zeb1. DKAT cells also express progenitor-cell markers, and single DKAT cells are able to generate tumorspheres containing both epithelial and mesenchymal cell types. In vivo, as few as ten DKAT cells are capable of forming xenograft tumors which display a range of epithelial and mesenchymal phenotypes. Finally, we also show evidence of vimentin expression in mammary epithelial cell clusters from asymptomatic women at high risk for breast cancer, suggesting that changes characteristic of epithelial-mesenchymal plasticity may be inherent to some breast cancers from their earliest stages.</p><p>Our results provide evidence that the aggressive behavior of a subset of triple-negative breast cancers is driven by inherent epithelial-mesenchymal plasticity. The novel finding that IL-6 regulates Zeb1 expression adds further rationale for the development of anti-IL-6 therapeutics, which will have the potential to target pathways at the intersection of metastasis and tumor recurrence. The DKAT cell line represents a novel model for further study of the molecular mechanisms that regulate plasticity in highly aggressive triple-negative breast cancers. An improved understanding of the pathways that are critical for this plasticity may lead to improved treatment options for highly aggressive and deadly breast cancers.</p> / Dissertation

Investors, stock exchanges and financial regulatory institutions can be used as strong levers for making firms accountable for achieving sustainable operational performance and not just maximizing profits. The objective of this research study is to enhance the quantitative tools available to stakeholders for evaluating relative operational performance of firms, thereby encouraging the financial investors to base their portfolio investment decisions on the basis of sustainable operational performance of firms. The study reviews the existing literature on evaluating relative operational performance of firms on sustainability metrics and proposes multi-level multi criteria decision making (MCDM) quantitative methods for measuring the same. The research work demonstrates the research framework proposed in the study by evaluating the 2014 Sustainable Operational Performance of firms in the oil & gas sector. The reason for choosing the oil & gas sector for this case study is in view of the relative large ecological and social impact which this industry has on different stakeholders. Due to the same reasons, the oil & gas sector is a bit more advanced in terms of its sustainability performance reporting standards. The review of past literature and the sustainability reports of firms for the year 2014 is initially used to develop the construct for measuring the firm operational performance on three pillars of TBL i.e. for the ecological, social and economic dimensions. / February 2017

In this thesis we investigate a system of three tunnel-coupled quantum dots, arranged in a triangular geometry and attached to a single metallic conduction band, using both analytic and semi-analytic methods and the numerical renormalisation group technique. This is the simplest coupled quantum dot system to exhibit frustration. We study three different models of the triple quantum dot device: a mirror symmetric arrangement of dots in which only one dot is connected to the conduction band, a triple quantum dot system in which only one dot is connected to the conduction band without a plane of mirror symmetry and a mirror symmetric arrangement of quantum dots in which all three dots are coupled to the conduction band. We study these models over a wide range of parameter space, and in both the presence and absence of a magnetic field. Both antiferromagnetic and ferromagnetic Kondo effects are observed, and in all three models we find that the system contains at least two phases, and so a number of quantum phase transitions may be observed, associated in some cases with significant changes in the low temperature conductance through the triple quantum dot device. In addition to zero-field Kondo physics, a number of field induced Kondo effects are also observed. Both first order quantum phase transitions and Kosterlitz-Thouless phase transitions are observed. We use both symmetry arguments and low energy effective models which we derive to explain and understand both the position of and type of phase boundary that is observed in each case, and perturbative methods are used to accurately predict Kondo temperatures for a wide range of systems.

In this paper we extend the study of Heffter arrays and the biembedding of graphs on orientable surfaces first discussed by Archdeacon in 2014. We begin with the definitions of Heffter systems, Heffter arrays, and their relationship to orientable biembeddings through current graphs. We then focus on two specific cases. We first prove the existence of embeddings for every K_(6n+1) with every edge on a face of size 3 and a face of size n. We next present partial results for biembedding K_(10n+1) with every edge on a face of size 5 and a face of size n. Finally, we address the more general question of ordering subsets of Z_n take away {0}. We conclude with some open conjectures and further explorations.

Le cancer du sein triple négatif (TNBC) représente entre 15-20% des cancers du sein et est l'un des types les plus agressifs. De plus, un sous-groupe de ces patientes est résistant à la radiothérapie (RT) et développe fréquemment une récidive hâtive de la maladie. Des études précédentes ont démontré que l’inflammation induite par la RT accélère la progression du cancer et le développement des métastases. Cette hypothèse a donc été validée dans un modèle pré-clinique de TNBC en implantant les cellules de carcinome de souris triple négatives D2A1 dans les glandes mammaires de la souris Balb/c. Premièrement, la tumeur primaire à été irradiée à une dose sous-curative une semaine post-implantation des cellules. En deuxième lieu, le tissu mammaire de la souris a été pré-irradié avant d'implanter les cellules cancéreuses afin de bien discerner l'effet du microenvironnement irradié sur celles-ci. Ces deux modèles ont mené à une augmentation significative des cellules tumorales circulantes ainsi que du nombre de métastases pulmonaires. Plusieurs molécules inflammatoires dont l'interleukine-1 bêta (IL-1β), l'interleukine-6 (IL-6) ou encore la cyclooxygénase 2 (COX-2) ont été identifiées comme facteurs clés impliqués dans la migration radio-induite des cellules cancéreuses du sein. Conséquemment, un inhibiteur large-spectre comme la chloroquine (CQ), entre autres utilisé comme traitement anti-malarien et anti-inflammatoire, a su prévenir ces effets secondaires associés à la RT. Étant donné que l'action de la CQ est peu sélective, une répression de l'expression de l'ARNm de la métalloprotéinase (MMP) de membrane de type 1 (MT1-MMP), une MMP de surface impliquée notamment dans la migration cellulaire, l'invasion tumorale et l'angiogenèse, a été réalisée afin d'éclaircir le mécanisme d'inhibition des métastases radio-induites. Cette répression de la MT1-MMP prévient la formation des métastases pulmonaires radio-induites, démontrant ainsi un des mécanisme important de l'invasion radio-induite. Ce résultat confirme donc l'importance de la MT1-MMP dans ce phénomène et son potentiel comme biomarqueur de prédiction de l'efficacité des traitements de RT, particulièrement chez les patientes atteintes de TNBC.

Ce travail de thèse expérimental porte sur les dynamiques d'imbibition en milieu confiné. Cette situation survient lorsqu'un fluide mouillant les parois d'un solide vient déplacer un second fluide non-miscible. La divergence des contraintes visqueuses au niveau de la ligne de contact avec le solide complexifie la description de la forme et de la dynamique d'invasion du ménisque qui ne peut se résumer, même aux échelles macroscopique du confinement solide, à l'avancement d'un front liquide homogène. L'absence de longueur caractéristique intrinsèque aux fluides nécessite de tenir compte des couplages entre écoulement et forme des interfaces à toutes les échelles, depuis le nanomètre (interactions moléculaires) jusqu'à l'échelle du confinement (une centaine de micromètres dans nos expériences). Ce caractère multi-échelle est au centre des travaux effectués durant cette thèse. A l'aide du développement de nouveaux outils microfluidiques, nous étudions quantitativement l'imbibition dans une géométrie de type Hele-Shaw. Une étude à la fois expérimentale et numérique nous permet de mettre en évidence l'existence d'une nouvelle transition d'entrainement. Une étude complète du modèle numérique nous permet ensuite d'unifier ce nouveau mode avec celui reporté jusqu'à présent dans la littérature. Nous nous intéressons aussi à l'imbibition dans des réseaux poreux modèle. Nous identifions alors expérimentalement un nouveau mode d'invasion généralisant l'entrainement obtenu précédemment. Ce scénario est piloté par l'écoulement en film de coin autour des obstacles constituant le poreux. Nous proposons alors un critère géométrique simple pour discriminer les différents modes d'invasions. / This experimental thesis deals with imbibition in confined media. This situation occurs when a fluid which preferentially wets the solid displaces another immiscible fluid. The divergence of the viscous stress at the contact line with the solid complicates the description of both the shape and the invasion dynamic of the meniscus that can no longer be described, even at the macroscopic length scale of the solid confinement, by only the displacement of a homogeneous liquid front. The absence of any intrinsic fluids length scale requires to take into account the coupling between the interface shape and the flow at all scales, from nanometers (molecular interaction) to solid confinement scale (hundred micrometers in our experiments). Multi-scale behavior will be the central point of this thesis. Using new microfluidics tools, we first made a quantitative study of imbibitions in Hele-Shaw geometry. We demonstrate a new class of liquid entrainment transition both experimentally and numerically. In addition, an extensive analysis of our numerical model shows that it consistently describes all scenarios that have been reported so far. We then study imbibitions in model porous media. We demonstrate a new invasion process, where the flow occurs along the corner of the porous? obstacles, that generalizes the previous entrainment. We finally propose a geometric criterion that discriminates between the different invasion scenarios.

Colon and breast cancers are amongst the leading causes of cancer deaths in the United States, mostly attributed to metastasis and resistance to therapy. Hence, there is a critical need to identify novel biomarkers for effective prognosis and to design targeted therapies to combat the metastatic diseases. Loss of heterozygosity (LOH) at chromosome 18q and inactivation of the target gene, SMAD4, corresponds to resistance to the common chemotherapeutic agent, 5-fluorouracil (5-FU), in colon cancer. Our examination of the therapeutic resistance phenomenon in SMAD4-negative colon cancer cells with the three common agents revealed significant resistance to both 5-FU and irinotecan but not to oxaliplatin. We also followed up with the earlier findings from our group, which suggested that SMAD4 might interact with metastasis-promoting factors to suppress metastatic progression and render sensitivity to chemotherapy. Co-immunoprecipitation and mass spectrometry analysis revealed that SMAD4 interacts with and inhibits RICTOR, a component of mTORC2 that activates oncogenic AKT via phosphorylation at Serine 473. Overexpression of SMAD4, depletion of RICTOR, or inhibition of AKT signaling restores sensitivity to irinotecan in SMAD4-negative colon cancer cells in vitro. Furthermore, as expected pharmacological inhibition of AKT sensitizes these cells to irinotecan in vivo. Interestingly, high RICTOR/AKT expression correlates with worse survival in colon cancer patients, suggesting them as novel prognostic biomarkers and therapeutic targets. On the other hand, triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer due to lack of effective targeted therapies. Using miRNA expression profiling of a model for epithelial-mesenchymal transition in TNBC, we found suppression of miR-4417 during the progression from non-malignant to malignant stage. Furthermore, localization of miR-4417 to chromosome 1p36, a region corresponding to high frequency of LOH in multiple cancers and low-level expression in TNBC patients associated with poor overall survival is consistent with its likely role as a tumor suppressor. Interestingly, we found that overexpression of miR-4417 is sufficient to inhibit migration and tumorigenecity of TNBC cells in vitro. Overall, our findings suggest miR-4417 exerts a tumor-suppressive effect and could serve as a novel prognostic biomarker and therapeutic tool against TNBC. / 2021-02-20T00:00:00Z

Biotechnology entrepreneurship is a relatively new and distinct field of entrepreneurship. Most current empirical research is conducted in the developed economies and cannot be directly extrapolated to the developing economies. The paucity of empirical research and the lack of a conceptual framework for biotechnology entrepreneurship constitute gaps that this research addressed through the development of a proposed theoretical framework of biotechnology entrepreneurship based on empirical research conducted within the context of the developing economies of South Africa and Brazil. The current methodological approaches to research in biotechnology entrepreneurship predominantly make use of a nomothetic philosophical approach and employs quantitative methods. Current research is also often based on surveys conducted within one developing economy context. Consequently, few studies in biotechnology entrepreneurship use the qualitative multiple case study approach. This methodological gap is addressed in this research through the use of qualitative multiple case studies, in the idiographic philosophical tradition, in two developing economies; South Africa and Brazil. The data collection process included in-depth interviews, documents review and observations, which improved the quality of the research through data triangulation. Ten themes were identified, which formed the basis for developing the proposed theoretical framework. In addition, seven factors that influence the process of biotechnology entrepreneurship in South Africa and Brazil were identified as regulation; funding; infrastructure; skills; entrepreneurial and commercialisation capabilities; market for biotechnology products; and social development. This research shows that the individual-opportunity nexus of entrepreneurship does not entirely hold for biotechnology entrepreneurship in South Africa and Brazil. Instead, there is a nexus of research and development; and a governmentincentivised environment that is conducive for biotechnology entrepreneurship. The policy implications of these dynamics in South Africa and Brazil; as well as implications for the other stakeholders in the biotechnology industry are articulated as being linked to the control of the factors that influence biotechnology entrepreneurship by the various stakeholders. Hence, the implications for government are predominantly linked to regulation and infrastructure; and the implications for the other stakeholders are predominantly linked to funding and skills.

Purpose - Considering personality as changeable through a bottom-up process of altering states, habits and traits, constitutes a shift in the predominant paradigm within personality psychology. The purpose of this paper is to reconsider Bateson's theory of learning and organizational triple-loop learning in light of this recent empirical evidence. Design/methodology/approach - This paper uses a multi-disciplinary conceptual approach. Based on an integrative analysis of literature from recent work in personality psychology, four dimensions (process, content, time and context) are identified that allow linking personality change and triple-loop learning. Findings - Identifying a bottom-up process of changing states, habits and traits as being central to change personality, allows for reconsidering Bateson's theory of learning as a theory of personality development (Learning II) and personality change (Learning III). Functionally equivalent, organizational triple-loop learning is conceptualized as a change in an organization's identity over time that may be facilitated through a change in responding to events and a change in the organization's routines. Practical implications - Interventions that change how organizations respond to events and that change the routines within an organization may be suitable to facilitate triple-loop learning in terms of changing organizational identity over time. Originality/value - This paper contributes to the discussion on Bateson's theory of learning and organizational triple-loop learning. As interest in personality change grows in organization studies, this paper aims to transfer these findings to organizational learning.