A Study of Female Sport Fans with Respect to Fantasy Sport Participation

Female sport fans make up ~40% of all North American big league sport fans. However, female sport fans make up only 20% of all fantasy sport participants. This study asked: why is there an under-representation of female participation in fantasy sports? In order to answer this question, 35 female sport fans who do not participate in fantasy sports were separated into five focus groups to provide the data necessary for this study. Seven themes emerged to explain why there is an under-representation of female participation in fantasy sports: lack of time, their friends do not play, negative associations, control versus escape, sport statistics, team versus player allegiances, and males acting as gatekeepers. Finally, four recommendations were made for those marketing fantasy sports to female sport fans: increase the overall awareness of fantasy sports, promote the social aspects of fantasy sports, streamline fantasy sports, and promote the ease of use.

Les effets de l'européanisation de la lutte contre la migration irrégulière sur les droits humains des migrants

Les politiques migratoires européennes sont conçues en termes de contrôle de l’entrée et du séjour des étrangers. Depuis la mise en place des conditions de libre circulation dans les années 1980, l’Union européenne est impliquée dans le traitement des non-nationaux qui, auparavant, relevait exclusivement de la discrétion étatique. La migration et l’asile sont aujourd’hui des domaines de compétence partagée entre l’Union et ses membres. La priorité est accordée à la lutte contre la migration irrégulière, perçue non seulement comme un défi à la souveraineté, mais aussi comme une menace à l’État providence et un risque pour la sécurité. Cette recherche porte sur l’européanisation de la lutte contre la migration irrégulière et ses effets sur les droits humains des étrangers. Il est soutenu que l’européanisation définie comme un processus de construction, de diffusion et d’institutionnalisation des normes, des pratiques et des convictions partagées, permet aux États d’atteindre leur objectif de limiter le nombre d’étrangers indésirés, y compris des demandeurs d’asile, sur leur sol. L’européanisation légitime et renforce les mesures préventives et dissuasives existantes à l’encontre des migrants clandestins. De nouvelles normes communes sont produites et de nouveaux dispositifs de coopération européenne sont créés en vue de réprimer la migration irrégulière. Ce phénomène transforme le paradigme migratoire dans les États membres ainsi que les pays candidats à l’adhésion qui se trouvent désormais chargés de la sécurisation des frontières extérieures de l’Union. La recherche démontre que ces développements ont un impact négatif sur les droits fondamentaux. Ils exacerbent aussi la vulnérabilité des demandeurs d’asile assimilés aux migrants économiques. Une analyse comparative de l’européanisation du renvoi forcé en France, au Royaume-Uni et en Turquie montre que la politique européenne engendre des atteintes aux droits et libertés des étrangers et limite leur capacité de contester les violations devant les tribunaux. L’accent est mis sur la nécessité de trouver un équilibre entre la préoccupation légitime des États et de l’Union d’assurer la sécurité et le bien-être de leurs citoyens et la protection des droits des migrants irréguliers. Il revient ultimement aux tribunaux de veiller à ce que le pouvoir discrétionnaire étatique s’exerce en stricte conformité avec les normes constitutionnelles et les obligations internationales découlant du droit international des réfugiés et des droits de l’homme.

El paradigma del Desarrollo Urbano Sostenible -DUS- como referente del proceso de toma de decisiones legislativas en Colombia. Análisis de la agenda legislativa del Congreso de la República entre 1991 y 2006

Este trabajo contribuye al análisis de la incidencia del paradigma del Desarrollo Urbano Sostenible en el proceso de toma de decisiones legislativas en Colombia, concentrándose en la discusión y definición de la agenda legislativa sobre asuntos urbanos, durante el periodo 1991-2006.

Disabled access and heritage attractions

In a UK context, the importance of heritage tourism, the potential of the disabled market, and government policies concerning tourism, social inclusion, and the historic environment provide the setting within which access improvements at heritage attractions for disabled visitors are studied. At issue is how disabled access and conservation can be reconciled. The stakeholders range from the central actors, the disabled tourists and the heritage tourism service providers, through to the gatekeeper and lobby players in the conservation, disability, and tourism contexts. The critical power structures are identified. Changes to the historic environment are managed through the conservation planning system in which disability interests are not formally represented. Recent disability discrimination legislation has not altered this balance of power, and is a source of uncertainty over the access standards that should apply to heritage attractions. An evaluation of progress in implementing access improvements at heritage attractions reveals the limited extent of improvements undertaken to date. Consideration is given not only to physical access but also to alternative methods (intellectual access) of providing the heritage tourism service. In conclusion, the situation is examined from three perspectives. From the disabled tourists' perspective, choice of heritage attractions to visit remains restricted compared to that of nondisabled tourists. The lack of consultation with disabled stakeholders in the access improvements decision-making process is discussed, including the acceptability of alternative methods of service delivery to disabled tourists. The uncertainties facing heritage tourism service providers arising from the disability discrimination legislation are considered but, to ensure a more balanced recognition of disability interests, both conservation planning and disability discrimination legislation need to be amended, adjusting the roles of the legislative gatekeepers.

Neocolonialism and international law, with specific reference to customary counterterrorism obligations and the principle of self-defence

Has international law ever, and, if it has not, can it ever, truly freed itself from the strictures of neocolonialism and the drive by a privileged elite to dominate the world scene? This article begins by inquiring into the nature of neocolonialism and, in so doing, pays particular attention to the writings of former Ghanaian President Kwame Nkrumah. It then proceeds to determine how neocolonialist designs surface in international law today by briefly looking at two aspects of international law in particular, namely customary international law, with specific reference to the counterterrorism context, and the principle of self-defence. In the final analysis, this article argues for a necessary and eternal scepticism of international law and the agendas of its privileged gatekeepers. Like classic State power, it opens itself to, and often operates as, neocolonial overreach, and to quote Nkrumah, “[t]he cajolement, the wheedlings, the seductions and the Trojan horses of neo-colonialism must be stoutly resisted, for neo-colonialism is a latter-day harpy, a monster which entices its victims with sweet music.”

Negotiating access into firms: obstacles and strategies

Researchers often experience difficulties with the negotiation of access into firms for the purpose of data collection. The question we explore is: What are the main obstacles associated with access negotiation into firms; and what strategies do researchers employ to increase their chances of success? Our research work on the tendering process of contractors took place between 2006 and 2008. We successfully negotiated access into four firms (two each in Ghana and the UK) to observe live examples of tender preparation The techniques we employed in negotiating access were personal contacts, contacting firms through online details and professional institutions, etc. With all of this effort, our average success rate was less than 5 per cent. The main obstacles encountered were firms’ reluctance because of commercial sensitiveness and fear that the data could eventually be divulged to their competitors or end up in the public domain. However, some firms agreed mainly because of the written assurances of confidentiality and anonymity in reporting the study; reputation of the researchers’ academic institution; gatekeepers who spoke to their colleagues on our behalf; academic purpose of the study; and a feedback report which was promised in return for access to the case studies. Although the access through personal contacts is by far the easiest, it is not always possible. Researchers can approach firms as complete strangers, especially in a foreign country, and that could make the firms more likely to assist the research.

Interviewing children and young people with learning disabilities: guidelines for researchers and multi-professional practice

We argue that it is important for researchers and service providers to not only recognize the rights of children and young people with learning disabilities to have a ‘voice’, but also to work actively towards eliciting views from all. A set of guidelines for critical self-evaluation by those engaged in systematically collecting the views of children and young people with learning disabilities is proposed. The guidelines are based on a series of questions concerning: research aims and ethics (encompassing access/gatekeepers; consent/assent; confidentiality/anonymity/secrecy, recognition, feedback and ownership; and social responsibility) sampling, design and communication

Não estou nisto para ganhar dinheiro: discurso e prática nas indústrias de criação

O estudo das indústrias de criação representam uma rica contribuição para a abordagem da estratégia como prática. Por se tratar de um ramo industrial simbólico-intensivo, as organizações nele inseridas adotam estratégias difusas que buscam conciliar lógicas tanto econômicas quanto não-econômicas, pois estas últimas são aquelas que garantem sua legitimidade e sobrevivência no campo. O universo simbólico, por sua vez, é volátil e cujo controle, por parte das organizações, é virtualmente impossível. Neste tipo de indústria, a abordagem sociológica em estratégia parece mais adequada para se compreender as ações dos agentes do campo organizacional em seu todo, não somente em seus aspectos instrumentais. Esta dissertação aborda os discursos e práticas imersos no contexto social do ramo editorial, por meio de um estudo longitudinal de dados secundários que adota uma versão adaptada para a estratégia do modelo discursivo de institucionalização como estrutura de análise. O objetivo principal da pesquisa era compreender como se articulam discursos e práticas num campo onde as regras de legitimação seguem uma lógica anti-econômica e onde os resultados econômicos nem sempre são o objetivo único das organizações. Adotou-se o conceito de orientação estratégica como a predisposição de uma organização para adotar uma ou outra estratégia, revelada por meio dos discursos e práticas organizacionais indicativos da interpretação reflexiva dada pelas organizações a seu contexto ambiental. Com base em dados coletados durante cerca de 3 anos pelo site de clipping de notícias do setor editorial Publishnews, foi utilizada uma metodologia de análise de conteúdo para interpretar o contexto ambiental, em suas facetas institucional e técnica, e as orientações estratégicas das editoras brasileiras, reveladas a partir dos textos e ações públicas presentes nas notícias. Em face das análises realizadas, constataram-se os resultados a seguir. Primeiramente, foi possível a descrição tanto do contexto ambiental como das orientações estratégicas por meio dos discursos e práticas. Do ponto de vista teórico, confirmou-se que os discursos são parte integral das orientações estratégicas das editoras, se articulando com as práticas, mesmo com aparentes dissonâncias entre elas, que se mostraram na verdade dissimuladas. Os discursos, como parte da estratégia, se apresentavam mais relevantes e mais utilizados quanto mais simbólicos fossem os objetivos a serem alcançados. Também se comprovou que, neste tipo de ramo, as orientações estratégicas dialogam mais com o ambiente institucional do que com o ambiente técnico, pois é no primeiro que podem ser obtidas as diferenciações de mercado, por meio de sub-produtos como legitimidade, mistificação ou consagração. As editoras também se orientam estrategicamente com mais intensidade sobre os chamados gatekeepers do que sobre seu mercado consumidor final, pois os primeiros é que garantem, ao gerar sub-produtos, a atração dos recursos mais raros (autores e recursos humanos), fundamentais para a sobrevivência num ramo simbólico-intensivo. Do ponto de vista prático, o uso da ferramenta metodológica proposta revelou que a dicotomia estratégica entre pequenas e grandes editoras é uma forma simplista de ver grupos estratégicos, ignorando estratagemas fundamentais que fogem à lógica econômica. A análise também mostrou traços de uma visão capitalista arcaica dominante no mercado nacional, arraigada em boa parte das editoras, ressaltada pelo excesso de demandas e delegação de responsabilidades ao Governo Federal, e da mistificação e valorização excessiva do universo livreiro. Editoras cujas orientações se mostravam opostas a estas obtiveram sucesso em criar novos mercados. Finalmente a dissertação coloca em dúvida os dados econômicos disponíveis sobre o mercado, freqüentemente usados como justificativa para políticas e demandas públicas, mas que parecem não se sustentar de forma alguma na realidade.

Food waste in lower-middle income households: a qualitative analysis of antecedents and a typology of food wasters

Esta dissertação doutoral, com base em dados empíricos coletados com 50 mães distribuídas no Brasil (n = 30) e nos EUA (n = 20), tem como objetivo fornecer uma melhor compreensão do desperdício de alimento no contexto da baixa renda. A tese é composta por três artigos, que combinados, cumprem os objetivos de identificar os antecedentes do desperdício de alimento e delinear uma tipologia dos desperdiçadores de alimento. Adicionalmente, contextualiza o desperdício global e um capítulo propõe uma agenda futura para estudos sobre desperdício de alimento no âmbito do consumidor. O desperdício de alimento nas famílias, enquanto tema de pesquisa, oferece a oportunidade para o trabalho acadêmico em marketing cumprir os critérios de relevância social, gerencial e para políticas públicas. No primeiro estudo, descrevem-se os fatores do chamado "paradoxo do desperdício de alimento", a identificação e análise do desperdício de alimento em famílias com restrições orçamentárias, enquanto apresentam-se o itinerário do consumo de alimentos e os antecedentes do desperdício. Este primeiro artigo, elaborado com dados coletados em famílias brasileiras, ilustra também o papel das normas culturais, tais como o preparo abundante de alimento para mostrar hospitalidade ou como forma de não ser percebido como pobre, no aumento do desperdício. No segundo artigo, uma grounded-theory (teoria fundamentada nos dados) destaca o papel do afeto e da abundância no desperdício de alimento familiar. Para enriquecer as contribuições teóricas, este segundo estudo apresenta um framework com seis dimensões do desperdício de alimento (1. Afeto; 2. Abundância; 3. Multiplicidade de escolhas; 4. Conveniência; 5. Procrastinação; 6. Rotina sem planejamento). Baseado em dados empíricos coletados em famílias americanas, este estudo proporciona novas explicações, a exemplo de como o estoque abundante de comfort foods - uma forma de impulsionar tanto emoções positivas para si quanto mostrar afeto para crianças – pode gerar mais desperdício de alimentos. Em síntese, o segundo artigo identifica uma consequência negativa do afeto e da abundância de alimentos no contexto familiar, e apresenta um framework teoricamente relevante. Finalmente, o terceiro artigo, a partir do conjunto de dados dos estudos anteriores e de nova coleta com dez famílias, propõe uma tipologia comportamental do desperdício de alimento, uma contribuição original aos estudos de comportamento do consumidor. A identificação de cinco tipos de desperdiçadores de alimentos - (1) Mães carinhosas; (2) Cozinheiras abundantes; (3) Desperdiçadoras de sobras; (4) Procrastinadoras; (5) Mães versáteis - contribui para a teoria, enquanto implicações potenciais para educadores nutricionais e agentes públicos são exploradas a partir dos resultados. Como uma forma de explicar as características de cada um dos cinco tipos identificados, compara-se aspectos das amostras brasileira e norte-americana, que apresentam similaridades no comportamento de desperdício de alimento. Os níveis de desperdício percebidos por país também são comparados. Em suma, os achados dos três artigos podem contribuir para maximizar os resultados de campanhas de conscientização voltadas à mitigação do desperdício de alimento, e apresentam ideias para varejistas interessados em iniciativas de sustentabilidade. Mais abrangentemente, os resultados apresentados também podem ser aplicados para incrementar programas de combate à fome e projetos de educação nutricional realizados pelo setor público ou ONGs.

Teaching medical students about dementia: a brief review

Underdeveloped nations have the largest absolute number of the world's elderly population. Approximately 10.7% of the Brazilian population comprises aged individuals. Aging populations are associated with a higher incidence of chronic degenerative diseases such as dementia. Demented individuals place a high burden of care on healthcare systems and family members. General practitioners should be able to diagnose the most common elderly diseases such as dementia since they act as gatekeepers to specialized care. In Brazil, many medical students work as general practitioners upon graduating. The present study shows some scenarios of medical schools worldwide, including Brazilian, regarding teaching on dementia.

Securitization and Special Purpose Vehicles in an International Setting: a Systemic View

The present work tries to display a comprehensive and comparative study of the different legal and regulatory problems involved in international securitization transactions. First, an introduction to securitization is provided, with the basic elements of the transaction, followed by the different varieties of it, including dynamic securitization and synthetic securitization structures. Together with this introduction to the intricacies of the structure, a insight into the influence of securitization in the financial and economic crisis of 2007-2009 is provided too; as well as an overview of the process of regulatory competition and cooperation that constitutes the framework for the international aspects of securitization. The next Chapter focuses on the aspects that constitute the foundations of structured finance: the inception of the vehicle, and the transfer of risks associated to the securitized assets, with particular emphasis on the validity of those elements, and how a securitization transaction could be threatened at its root. In this sense, special importance is given to the validity of the trust as an instrument of finance, to the assignment of future receivables or receivables in block, and to the importance of formalities for the validity of corporations, trusts, assignments, etc., and the interaction of such formalities contained in general corporate, trust and assignment law with those contemplated under specific securitization regulations. Then, the next Chapter (III) focuses on creditor protection aspects. As such, we provide some insights on the debate on the capital structure of the firm, and its inadequacy to assess the financial soundness problems inherent to securitization. Then, we proceed to analyze the importance of rules on creditor protection in the context of securitization. The corollary is in the rules in case of insolvency. In this sense, we divide the cases where a party involved in the transaction goes bankrupt, from those where the transaction itself collapses. Finally, we focus on the scenario where a substance over form analysis may compromise some of the elements of the structure (notably the limited liability of the sponsor, and/or the transfer of assets) by means of veil piercing, substantive consolidation, or recharacterization theories. Once these elements have been covered, the next Chapters focus on the regulatory aspects involved in the transaction. Chapter IV is more referred to “market” regulations, i.e. those concerned with information disclosure and other rules (appointment of the indenture trustee, and elaboration of a rating by a rating agency) concerning the offering of asset-backed securities to the public. Chapter V, on the other hand, focuses on “prudential” regulation of the entity entrusted with securitizing assets (the so-called Special Purpose vehicle), and other entities involved in the process. Regarding the SPV, a reference is made to licensing requirements, restriction of activities and governance structures to prevent abuses. Regarding the sponsor of the transaction, a focus is made on provisions on sound originating practices, and the servicing function. Finally, we study accounting and banking regulations, including the Basel I and Basel II Frameworks, which determine the consolidation of the SPV, and the de-recognition of the securitized asset from the originating company’s balance-sheet, as well as the posterior treatment of those assets, in particular by banks. Chapters VI-IX are concerned with liability matters. Chapter VI is an introduction to the different sources of liability. Chapter VII focuses on the liability by the SPV and its management for the information supplied to investors, the management of the asset pool, and the breach of loyalty (or fiduciary) duties. Chapter VIII rather refers to the liability of the originator as a result of such information and statements, but also as a result of inadequate and reckless originating or servicing practices. Chapter IX finally focuses on third parties entrusted with the soundness of the transaction towards the market, the so-called gatekeepers. In this respect, we make special emphasis on the liability of indenture trustees, underwriters and rating agencies. Chapters X and XI focus on the international aspects of securitization. Chapter X contains a conflicts of laws analysis of the different aspects of structured finance. In this respect, a study is made of the laws applicable to the vehicle, to the transfer of risks (either by assignment or by means of derivatives contracts), to liability issues; and a study is also made of the competent jurisdiction (and applicable law) in bankruptcy cases; as well as in cases where a substance-over-form is performed. Then, special attention is also devoted to the role of financial and securities regulations; as well as to their territorial limits, and extraterritoriality problems involved. Chapter XI supplements the prior Chapter, for it analyzes the limits to the States’ exercise of regulatory power by the personal and “market” freedoms included in the US Constitution or the EU Treaties. A reference is also made to the (still insufficient) rules from the WTO Framework, and their significance to the States’ recognition and regulation of securitization transactions.

Protective role of autophagy and autophagy-related protein 5 in early tumorigenesis.

Autophagy, a fundamental cellular catabolic process, is involved in the development of numerous diseases including cancer. Autophagy seems to have an ambivalent impact on tumor development. While increasing evidence indicates a cytoprotective role for autophagy that can contribute to resistance against chemotherapy and even against the adverse, hypoxic environment of established tumors, relatively few publications focus on the role of autophagy in early tumorigenesis. However, the consensus is that autophagy is inhibitory for the genesis of tumors. To understand this apparent contradiction, more detailed information about the roles of the individual participants in autophagy is needed. This review will address this topic with respect to autophagy-related protein 5 (ATG5), which in several lines of investigation has been ascribed special significance in the autophagic pathway. Furthermore, it was recently shown that an ATG5 deficiency in melanocytes interferes with oncogene-induced senescence, thus promoting melanoma tumorigenesis. Similarly, an ATG5 deficiency resulted in tumors of the lung and liver in experimental mouse models. Taken together, these findings indicate that ATG5 and the autophagy to which it contributes are essential gatekeepers restricting early tumorigenesis in multiple tissues.

Federally regulated institutional review boards: The aspects of a "model" IRB---Is the current system in need of a tune up or complete overhaul?

Institutional Review Boards (IRBs) are the primary gatekeepers for the protection of ethical standards of federally regulated research on human subjects in this country. This paper focuses on what general, broad measures that may be instituted or enhanced to exemplify a "model IRB". This is done by examining the current regulatory standards of federally regulated IRBs, not private or commercial boards, and how many of those standards have been found either inadequate or not generally understood or followed. The analysis includes suggestions on how to bring about changes in order to make the IRB process more efficient, less subject to litigation, and create standardized educational protocols for members. The paper also considers how to include better oversight for multi-center research, increased centralization of IRBs, utilization of Data Safety Monitoring Boards when necessary, payment for research protocol review, voluntary accreditation, and the institution of evaluation/quality assurance programs. ^ This is a policy study utilizing secondary analysis of publicly available data. Therefore, the research for this paper focuses on scholarly medical/legal journals, web information from the Department of Health and Human Services, Federal Drug Administration, and the Office of the Inspector General, Accreditation Programs, law review articles, and current regulations applicable to the relevant portions of the paper. ^ Two issues are found to be consistently cited by the literature as major concerns. One is a need for basic, standardized educational requirements across all IRBs and its members, and secondly, much stricter and more informed management of continuing research. There is no federally regulated formal education system currently in place for IRB members, except for certain NIH-based trials. Also, IRBs are not keeping up with research once a study has begun, and although regulated to do so, it does not appear to be a great priority. This is the area most in danger of increased litigation. Other issues such as voluntary accreditation and outcomes evaluation are slowing gaining steam as the processes are becoming more available and more sought after, such as JCAHO accrediting of hospitals. ^ Adopting the principles discussed in this paper should promote better use of a local IRBs time, money, and expertise for protecting the vulnerable population in their care. Without further improvements to the system, there is concern that private and commercial IRBs will attempt to create a monopoly on much of the clinical research in the future as they are not as heavily regulated and can therefore offer companies quicker and more convenient reviews. IRBs need to consider the advantages of charging for their unique and important services as a cost of doing business. More importantly, there must be a minimum standard of education for all IRB members in the area of the ethical standards of human research and a greater emphasis placed on the follow-up of ongoing research as this is the most critical time for study participants and may soon lead to the largest area for litigation. Additionally, there should be a centralized IRB for multi-site trials or a study website with important information affecting the trial in real time. There needs to be development of standards and metrics to assess the performance of the IRBs for quality assurance and outcome evaluations. The boards should not be content to run the business of human subjects' research without determining how well that function is actually being carried out. It is important that federally regulated IRBs provide excellence in human research and promote those values most important to the public at large.^

Ethnic differences in food availability at home among 3--5 year old preschoolers attending Head Start centers in 2008

Background. The childhood obesity epidemic has disproportionately impacted the lives of low-income, minority preschoolers and their families. Research shows that parents play a major role as "gatekeepers" who control what food is brought into the home and as role models for dietary practices. Currently, there is limited research regarding ethnic differences in families of low-income preschoolers. ^ Objective. The objective of this study was to look at ethnic differences in food availability at home among the low-income families of Hispanic and African American preschoolers attending Head Start centers in Harris County, Texas. ^ Design/Subjects. Descriptive data on food availability at home between Hispanic and African American families were used and analyzed for this study. Parents or primary caregivers (n = 718) of children enrolled at Head Start Centers in Houston, Texas completed the Healthy Home Survey. ^ Methods. In the Healthy Home Survey, participants were asked to answer open-ended questions regarding various types of foods currently available at home, such as fresh, canned or jarred, dried and frozen fruits; fresh, canned or jarred, and frozen vegetables; salty snacks, sweet snacks, candy, and soda. Descriptive analyses were conducted to identify significant differences between Hispanics and African Americans via a paired t-test to compare the means of variables between the study groups and a Pearson's chi-square or Fischer's exact (if cell size was <5) test calculated for food availability (food types) between ethnicities to determine differences in distributions. ^ Results. Although both Hispanics and African Americans reported having all categories of food types at home, there were statistically significant differences between ethnic groups. Hispanics were more likely to have fresh fruits and vegetables at home than African Americans. At the same time, more African American families reported having canned or jarred fruits and canned green/leafy vegetables than Hispanics. More Hispanic families reported having diet, regular, and both diet and regular sodas available compared to African American families. However, high percentages of unhealthy foods (including snacks and candy) were reported by both ethnicities. ^ Conclusions. The findings presented in this study indicate the implicit ethnic differences that exist in the food availability among low-income families of Hispanic and African American preschoolers. Future research should investigate the associations between food availability and children's weight status by ethnicity to identify additional differences that may exist.^

Critical determinants of estrogen receptor -mediated agonist activity

Exogenous ligands that bind to the estrogen receptor (ER) exhibit unique pharmacologies distinct from that observed with the endogenous hormone, 17β-estradiol (ED. Differential activity among ER ligands has been observed at the level of receptor binding, promoter interaction and transcriptional activation. Furthermore, xenoestrogens can display tissue-specific agonist activity on the cellular level, functioning as an agonist in one tissue and as an antagonist in another. That the same ligand, functioning through the same receptor, can produce differing agonist responses on the cellular level indicates that there are tissue-specific determinants of agonist activity. In these studies critical molecular determinants of agonist activity were characterized for several cell types. In the normal and neoplastic myometrium a proliferative response was dependent upon activation of AF2 of the ER, functioning as a determinant of agonism in this cell type. Progesterone receptor (PR) ligands transdominantly suppressed ER-mediated transcription and proliferation in uterine leiomyoma cells, indicating that ER/PR cross-talk can modulate agonist activity in a myometrial cell background. In the breast, the agonist response to ER ligands was investigated by employing a functional genomics approach to generate gene expression profiles. Treatment of breast cancer cells with the selective estrogen receptor modulator tamoxifen largely recapitulated the expression profile induced by treatment with the agonist E2, despite the well-characterized antiproliferative effects produced by tamoxifen in this cell type. While the expression of many genes involved in regulating cell cycle progression, including fos, myc, cdc25a, stk15 and cyclin A, were induced by both E2 and tamoxifen in breast cells, treatment with the agonist E2 specifically induced the expression of cyclin D1, fra-1 , and uracil DNA glycosylase. These results suggest that the inability of tamoxifen to transactivate expression of only a few key genes, functioning as cellular gatekeepers, prevent tamoxifen-treated breast cells from entering the cell cycle. Thus, the expression of these agonist-specific marker genes is a potential determinant of agonist activity at the cellular level in the breast. Collectively, studies in the breast and uterine myometrium have identified several mechanisms whereby ER ligands modulate ER-mediated signaling and provide insights into the biology of tissue-specific agonist activity in hormone-responsive tissues. ^