<p>Chemotherapy remains the only available treatment for triple-negative (TN) breast cancer. Although some TN breast cancers respond initially to neoadjuvant chemotherapy, the majority of patients die within three years of treatment due to recurrent tumor growth. Developing ex vivo models for TN breast cancer recurrence and defining responsible molecules will be crucial to developing effective combination therapies for TN breast cancer patients. We have developed an in vitro model of TN breast cancer dormancy/recurrence. Short-term exposure of tumor cells to chemotherapy at clinically relevant doses enriches for a dormant tumor cell population. Several days after removing chemotherapy, dormant tumor cells regain proliferative ability and establish colonies, resembling tumor recurrence. Tumor cells from "recurrent" colonies exhibit increased chemotherapy resistance, resembling therapy resistance of recurrent tumors in patients. Furthermore, we identify a novel signaling axis [nuclear bFGF/DNA-dependent protein kinase (DNA-PK)] supported by chemotherapy-enriched dormant TN breast cancer cells. This signaling axis drives accelerated DNA repair in chemo-residual TN breast cancer cells. Targeting this axis with either with a bFGF shRNA or DNA-PK small molecule inhibitor blocks recurrent colony formation. Using the Oncomine gene expression database, we found that bFGF expression in tumor samples from TN breast cancer patients predicts five year tumor recurrence following neoadjuvant chemotherapy treatment. Finally, we demonstrate that recurrent tumor cells exhibit increased invasiveness, reflecting the aggressive behavior of recurrent tumors in patients. Collectively, these studies identify a novel signaling axis in TN breast cancer that likely contributes to tumor recurrence and provide molecular targets for developing future therapeutics against TN breast cancer.</p> / Dissertation

This study examines Corporate Social Responsibility in Sustainable Development and the notion of the Triple Bottom Line as an imperative in today’s socially responsible corporation. Standardization is used as a tool for integrating social and environmental costs and benefits into the financial bottom line of an organization. This research aims to discover what standards or methods are used to measure social and environmental progress in three organizations in Houston, Texas and the implied potential for CSR as a driver for profitability. The primary data included in this research was captured through semi-structured qualitative interviews with upper level management of the three companies included in the final study. The results consistently supported positive correlations between CSR and improvements in company image and stakeholder relations. One participant was also able to report evidence of increased profitability through cost containment as a result of their integration of CSR initiatives throughout their organization.

Sustainable development is one of the most frequently used expressions in the economic context. Its importance is emphasized not only at the national level but also at the corporate level. The purpose of this study is to find the influence of company´s age, size and type of industry on the level of sustainable development among Swedish companies. In order to accurately evaluate the level of sustainable development a comprehensive measurement scale is needed. We have recognized the research gap of lack of sustainability measurement methods. Thus, the second goal we have decided to achieve is to develop an extensive measurement scale for sustainability performance evaluation. The main contribution of the study lies in filling the research gap by providing a new measurement method that can be adopted in order to evaluate the sustainability performance and to find the effects of company age, size and type of industry on the level of CSR. The relationships in the study are hypothesized and summarized in the conceptual model and consequently tested. This study distinguishes five underlying perspectives of sustainability and several categories of company ages, size and types of industry. These aspects are in the focal point of the questionnaire sent to our sample of Swedish companies. The data collected from the survey were analyzed in SPSS statistics program using a variety of analytical methods. At first, each set of questions was analyzed separately. Thereafter, the findings regarding each determinant of CSR were thoroughly discussed. Based on the results from analytical tests a revised conceptual model is proposed. The new features added to the model should enhance its quality and explanatory value. The collected data reveal that the responding Swedish companies engage in the sustainability perspectives in a considerable extent. According to the results of the study there is no or minor effect of company age and type of industry on the level of CSR. Company size, however, is found to be a significant determinant of CSR causing an U-shaped effect. This U-shaped effect of company size implies that the level of CSR activities decreases as a company grows from small to middle-sized but increases from middle-sized to large company.

Avec l'augmentation de la probabilité de fautes dans les circuits numériques, les systèmes développés pour les environnements critiques comme les centrales nucléaires, les avions et les applications spatiales doivent être certifies selon des normes industrielles. Cette thèse est un résultat d'une cooperation CIFRE entre l'entreprise Électricité de France (EDF) R&D et Télécom Paristech. EDF est l'un des plus gros producteurs d'énergie au monde et possède de nombreuses centrales nucléaires. Les systèmes de contrôle-commande utilisé dans les centrales sont basés sur des dispositifs électroniques, qui doivent être certifiés selon des normes industrielles comme la CEI 62566, la CEI 60987 et la CEI 61513 à cause de la criticité de l'environnement nucléaire. En particulier, l'utilisation des dispositifs programmables comme les FPGAs peut être considérée comme un défi du fait que la fonctionnalité du dispositif est définie par le concepteur seulement après sa conception physique. Le travail présenté dans ce mémoire porte sur la conception de nouvelles méthodes d'analyse de la fiabilité aussi bien que des méthodes d'amélioration de la fiabilité d'un circuit numérique.

The aim of this study is to understand the Fair Trade Coffee Business Model by determining how the Fair Trade Coffee Business Model affects the livelihoods of the small scale producers in developing countries. The Fair Trade Coffee Business Model is driven by the mission to improve the well-being of the small scale producers located in developing countries through the lens of the Triple Bottom Line (economic, social and environment). What is the significance of fair trade coffee to the economies of developing countries that produce coffee? The economies are considerably impacted by coffee production as coffee ranks as the second foremost exported commodity from developing countries (European Coffee Federation, 2006). Ensuring the small scale producers receive a fair price for the coffee they grow is only one of the initiatives of the model. Other key initiatives include pre-harvest financing, increased healthcare services, working together for a higher quality coffee, fairer business conduct, improvements in education, and technical assistance. The findings of this study provide some insights into the Fair Trade Coffee Business Model’s effect on the livelihoods of the small scale producers in developing countries through the lens of the Triple Bottom Line. The Fair Trade Coffee Business Model has increased the quality of the coffee bean produced by the small scale producers along with developing long term business relationships throughout the Fair Trade Coffee Business Model supply chain. In sum, the small scale producers reported that the Fair Trade Coffee Business Model has a positive effect on their livelihood and well-being. More specifically, they also indicated that the motivations for them to participate in the Fair Trade Coffee Business Model are receiving a better price for coffee, democratic decision making and farm training. An additional finding affirms that the Fair Trade Coffee Business Model is a sound contributor to the socio-economic stability of the small scale producers, offering a sustainable income-generating alternative market strategy.

Alternative fuels and technologies for truckload carriers can provide significant environmental and social benefits over traditional heavy duty diesel vehicles by reducing petroleum-based fuel consumption and vehicle tailpipe emissions. These alternative fuels and technologies, however, often carry a cost premium or require significant capital investment. Dedicating vehicles, equipment, and infrastructure to an alternative fuel or technology also represents a significant risk in the extremely volatile trucking business. A Triple-Bottom-Line analysis, which includes economic, social, and environmental impacts of an alternative fuel or technology will strengthen the business case by incorporating the benefits of emissions reduction. A stronger business case will promote the use of alternative fuels and technologies while mitigating the risk. This thesis proposes a method for identifying alternative fuels and technologies that provide the best Triple-Bottom-Line benefit and provides a structure for modeling the emissions of the target application, quantifies the value of emissions reduction, and constructs a Triple-Bottom-Line business case. The Triple-Bottom-Line business case proposed by this method is incremental. It presupposes an existing or planned truckload carrier business already exists and only investigates the changes which occur with implementation of an alternative fuel or technology. This method may be useful for any carrier business or any company with an extensive shipping and logistics network. A case study, which was created for large automotive manufacturer, details the Triple-Bottom-Line business case for an on-site compressed natural refueling system and vehicles.

There have been many attempts to use mathematical method in order to characterize shale gas/oil reservoirs with multi-transverse hydraulic fractures horizontal well. Many authors have tried to come up with a suitable and practical mathematical model. To analyze the production data of a shale reservoir correctly, an understanding and choosing the proper mathematical model is required. Therefore, three models (the homogeneous linear flow model, the transient linear dual porosity model, and the fully transient linear triple porosity model) will be studied and compared to provide correct interpretation guidelines for these models. The analytical solutions and interpretation guidelines are developed in this work to interpret the production data of shale reservoirs effectively. Verification and derivation of asymptotic and associated equations from the Laplace space for dual porosity and triple porosity models are performed in order to generate analysis equations. Theories and practical applications of the three models (the homogeneous linear flow model, the dual porosity model, and the triple porosity model) are presented. A simplified triple porosity model with practical analytical solutions is proposed in order to reduce its complexity. This research provides the interpretation guidelines with various analysis equations for different flow periods or different physical properties. From theoretical and field examples of interpretation, the possible errors are presented. Finally, the three models are compared in a production analysis with the assumption of infinite conductivity of hydraulic fractures.

This thesis addresses two research objectives: i).empirically develop a taxonomy based on firms strategic Corporate Sustainable Development (CSD) orientation to better understand and describe their characteristics and business differentials; and ii).develop and empirically test an integrated framework of antecedents and consequences of the strategic CSD, including pathways and contingencies. The full study involves two consecutive steps: a qualitative study using in-depth interviews with senior marketing executives/experts from eight selected organisations; and a quantitative inquiry using an online survey, with a final sample of 183 medium to large Australian companies across manufacturing, mining and utilities/energy industries. Collectively, this two-stage study yields interesting research findings that are of substantial academic and managerial value as follows: The taxonomy analysis identifies three distinct groups: Strategic Achievers, Risk Avoiders and Suspicious Observers, that represent the three levels/stages of CSD adoption from high to low. These three clusters are described by what they do, why they do it, the major barriers and performance differentials. These findings contribute to the classification scheme and may assist managers to determine current levels of CSD, identify possible business opportunities and/or decide on the strategies of CSD adoption. Through developing CSD measures and testing the relationships within the proposed framework, Innovation Capability (IC) is found to be a pathway (mediator) for firms to gain competitive advantage from Corporate Sustainable Development, whereas CSD does not impact on Business Performance directly when IC is absent. This inconsistent mediating effect of IC provides interesting new insight. In addition, CSD exhibits a positive impact on firms Member Organisation Identification, a surrogate measure of corporate reputation from the perspective of employees. As part of the second research objective, this study also conducts the first empirical testing of the Menon and Menon (1997) model, and found that Industry Reputation moderated the Enviropreneurial Marketing and Business Performance relationship. These findings provide new knowledge concerning strategic Corporate Sustainable Development (CSD) orientation as well as the underlying mechanisms, which may inform managers with viable directions for integrating corporate economic benefits with social and environmental considerations.

Theses (Ph. D.)--Marshall University, 2004. / Title from document title page. Includes abstract. Document formatted into pages: contains xiv, 192 p. including illustrations. Bibliography: p. 157-192.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Diante do estreitamento do horizonte emancipatório para uma parcela significativa da população brasileira, procuramos, neste estudo, descrever a história real destes muitos, para não dizer milhões, que acabaram condenados à margem de formas sociais, econômicas, estilísticas, consagradas pelos aparatos ideológicos que perpetuam e justificam a reprodução da racionalidade do capital como o único e exclusivo sistema social. Na contemporaneidade, a mercantilização da vida em sociedade e seu indissociável processo de descartabilidade marcam presença constante no cenário das médias e grandes cidades brasileiras. Perscrutando o campo exploratório, presenciamos grupos humanos cada vez mais desvinculados do sistema produtivo. Destituídos de qualidades aceitáveis circunscritas à esfera econômica e moral capitalista, figuram, apenas, como paisagem, apenas, como fragmentos do universo objetivo. Vidas em sobrestado permanente, confundidas e misturadas com o descartável, sem lugar no mundo produtivo, galgam a invisibilidade social. É esta incivilidade levada ao seu paroxismo chamada invisibilidade que, aqui, identificamos e trazemos à luz. Uma invisibilidade que se constrói não pelo olhar, mas num imaginário persistente que fixa a pobreza como marca de inferioridade, potencializando um modo de ser que descredencia indivíduos para o exercício de seus direitos e da vida social, já que percebidos numa diferença incomensurável, aquém das regras da equivalência, isto é, da alteridade que a formalidade da lei e o exercício dos direitos deveriam concretizar. É neste espaço de interpelação do outro que a invisibilidade se constitui. Ela habita o registro do impensável, do conflito com a ideia de essência, de alteridade que arbitra todas as formas de ser. O invisível surge como alguém que não É, provocação que incita o estranhamento, o que o torna assediado por um forte ranço moral que preserva a depreciação de tudo que perdeu o valor de uso. É assim decretada a sua tripla negação: desistoricizado, desumanizado e dessignificado, mesclado a um universo de contravalores que imobilizam a vida, tornando-o incodificável, um personagem inefável colocando em xeque toda a lógica da representação. Nossa proposta, com este trabalho, foi o de ir além de um trabalho documental, mas de constatação e denúncia, procurando ultrapassar visões reducionistas que naturalizam a pobreza e a miséria, reencontrando assim, nas mediações e contrapontos, as contradições fundas que conduzem muitos a invalidação social, cujas violações e mutilações, de toda ordem, prosperam a favor de uma ordem econômica que se apresenta desvinculada e independente de limites e de justificações morais / Given the narrowing of the emancipatory horizon for a significant portion of the Brazilian population, we seek in this study to describe the real story of these many, not to say millions, who ended up sentenced to the fringes of social, economic, stylistic forms enshrined by the ideological apparatuses which perpetuate and justify the reproduction of the rationality of capital as the only and exclusive social system. In contemporary times, the commodification of social life and its indissociable disposability process are constantly present in the scenario of medium and large Brazilian cities. By scrutinizing the exploratory field, we witness human groups being increasingly disconnected from the productive system. Devoid of acceptable qualities that are confined to the economic and moral capitalist sphere, they appear only as a landscape, just as fragments of the objective universe. Lives permanently halted, confused and mixed with the disposable, with no place in the productive world, reaching "social invisibility". It is this incivility taken to its paroxysm called "invisibility" that here we identify and bring to light. An "invisibility" which is built not by the look, but by a persistent imagery that sets poverty as a mark of inferiority, reinforcing a way of being that disqualifies individuals to exercise their rights and social life, perceived as an immeasurable difference below the rules of equivalence, i.e. the otherness that the formality of the law and the exercise of rights should achieve. It is through questioning each other that the "invisibility" is constituted. It abides in the records of the unthinkable, of the conflict with the idea of essence, of otherness that arbitrates all forms of "being". The invisible emerges as someone who ISNT, a provocation which encourages strangeness, which makes him harassed by a strong moral rancidity that preserves the depreciation of everything that has lost value. It is thus declared his triple denial: dishistoricized, dehumanized and insignificant, blended to a universe of countervalues which immobilize life, making him uncodifiable, an unfathomable character jeopardizing the entire logic of representation. Our proposal in this paper, was to go beyond a documentary work, but to verify and report, seeking to overcome reductionist views that naturalize poverty and misery, thus rediscovering, in mediations and counterpoints, the deep contradictions which lead many to social invalidation, whose violation and mutilation of all kinds thrive in favor of an economic order that appears detached and independent from limits and moral grounds