Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles.

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms

Reframing Kurtz’s Painting: Colonial Legacies and Minority Rights in Ethnically Divided Societies

Minority rights constitute some of the most normatively and economically important human rights. Although the political science and legal literatures have proffered a number of constitutional and institutional design solutions to address the protection of minority rights, these solutions are characterized by a noticeable neglect of, and lack of sensitivity to, historical processes. This Article addresses that gap in the literature by developing a causal argument that explains diverging practices of minority rights protections as functions of colonial governments’ variegated institutional practices with respect to particular ethnic groups. Specifically, this Article argues that in instances where colonial governments politicize and institutionalize ethnic hegemony in the pre-independence period, an institutional legacy is created that leads to lower levels of minority rights protections. Conversely, a uniform treatment and depoliticization of ethnicity prior to independence ultimately minimizes ethnic cleavages post-independence and consequently causes higher levels of minority rights protections. Through a highly structured comparative historical analysis of Botswana and Ghana, this Article builds on a new and exciting research agenda that focuses on the role of long-term historio-structural and institutional influences on human rights performance and makes important empirical contributions by eschewing traditional methodologies that focus on single case studies that are largely descriptive in their analyses. Ultimately, this Article highlights both the strength of a historical approach to understanding current variations in minority rights protections and the varied institutional responses within a specific colonial government

Reconstructing World Politics: Norms, Discourse, and Community

This Article argues that the conventional (rationalist) approach to world politics characterized by political bargain cannot fully capture the new social reality under the contemporary global ambience where ideational factors such as ideas, values, culture, and norms have become more salient and influential not only in explaining but also in prescribing state behaviors. After bringing rationalism’s paradigmatic limitations into relief, the Article offers a sociological framework that highlights a reflective, intersubjective communication among states and consequent norm-building process. Under this new paradigm, one can understand an international organization as a “community” (Gemeinschaft), not as a mere contractual instrument of its contracting parties (Gesellschaft). The Article applies the new paradigm to the World Trade Organization (WTO) as it describes the WTO’s institutional evolution from a power-oriented, tariff-reducing contract to a norm-oriented world trade community

The Interactions between the Business Strategies and Financial Strategies among the MNCs in Singapore

MNCs have been playing an overwhelming role in Singapore's economic development. Large Singapore MNCs tend to be more westernized. Although cultural differences exist, Singapore is open and pragmatic, and therefore permits Western practices to be introduced and become the preferred management style. As the economic activities in Asia become more competitive, MNCs in Singapore have also been redefining the role of their operations in Singapore � from pure manufacturing to regional headquarters services. As Singapore's economic success is mostly attributed to MNC' FDI inflow, it would require the identification, consideration, and analysis of many risk factors, tangibles as well as intangibles. Nevertheless, the MNCs must strategize to match corporate capabilities and at the same time grant some form of competitive advantage, thereby increasing the value of the company. The purpose of this dissertation is to examine the critical factors of corporate strategies that can affect the long-term performance of 18 MNCs in Singapore, so as to provide guidance for their survival and growth. The research examines the interactions between business and financial strategies, and discusses important propositions on growth and risk management based on relevant empirical and analytical findings from two business aspects: internationalization and product/service diversification and two financial aspects: asset liquidity and capital structure. The research also provide an analysis of the impact of internationalization strategy on asset liquidity and capital structure, the relationships between diversification strategy, asset liquidity and capital structure, as well as present the implications that are derived from these two analyses

KINEMATICS AND PHYSIOLOGICAL EFFECT OF A SYNCHRONIZED BIPEDAL “RISE-SIT-GO” CYCLING EXERCISE

This study demonstrated the kinematics and physiological effect of a synchronized bipedal cycling exercise. Fifteen male subjects performed a 30-minutes exercise on a synchronized bipedal stationary bike and a conventional stationary bike at same cycling speed. The performance was evaluated by a metabolic testing system, a subjective rating of perceived exertion, an electromyography system and a motion analysis system, and was compared by paired t-tests. Results showed significant increases in oxygen uptake, energy expenditure, rating of perceived exertion, muscle activity in triceps, biceps, rectus abdominis, left gluteus maximus, left medial gastrocnemius, right tibialis anterior and left tibialis anterior, and range of motion of left hip, left and right knees, shoulders, elbows and wrists. The synchronized bipedal cycling exercise was more physically demanding

Capturing genetic gains in productivity with heterosis

The National Swine Registry (NSR) has two long term goals: 1) to register purebred pigs and thus assure breed purity and 2) encourage genetic progress through performance testing - genetic selection programs. The continued production of purebred lines assures that a number of breeds are available to produce females and terminal cross pigs with high levels of heterosis. Purebred breeders, whose customers are commercial swine producers, have produced substantial rates of genetic progress by use of the STAGES program

Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union

Genetic improvement of meat quality and fertility using the national nucleus

Knowledge is power and the National Swine Registry (NSR) is the only source of complete, publicly available, genetic records on nucleus populations. NSR has offered STAGES \u27, a BLUP genetic improvement program with bio-economic indexes for over 17 years. NSR members submit information on 3 sow productivity traits and 3 postweaning performance traits and in return receive across-herd Expected Progeny Deviations (EPDs) for these traits along with indexes for Sow Productivity, Maternal Line (sow productivity and postweaning performance) and Terminal (postweaning traits only) to be used in genetic selection. Not only is this genetic information available to members but genetic values and trends for these traits are also available to any commercial producer or genetic advisor. This program has led NSR members to make substantial genetic improvement for these traits within all four breeds. In addition, this transparent system allows commercial producers to design programs and select animals that allow them the greatest potential for their situation. As the pork industry continues ro change, multiple pork chains are forming to meets distinct specifications desired by subsets of consumers. To continue to meet the demand of these dissimilar pork chains, differentiated genetic lines are necessary to provide products that match their specifications. In addition, as profit per pig continues to decline pork producers must be able to increase product sold per unit of investment. To facilitate this key profitability indicator, the fertility of breeding females must improve. To address these two key drivers in today\u27s pork industry, the NSR has updated their genetic improvement program in these two areas