so in a cursory manner. Actually, that would have been a good strategy for the whole book to give it an intersectional and more theoretically sophisticated analysis. My reservations notwithstanding, Is There Life after Football? is a well-researched book that provides useful insight and information. While I would have preferred a more traditionally academic text, it is still valuable to sociologists, sport scholars, and general readers interested in moving beyond media hyperbole. It is without a doubt the most detailed and thoughtful analysis of former NFL players’ transitions out of football.

The emergence of novelty, especially of new categories of people and organizations, is undertheorized in the social sciences. Some social worlds are more hospitable to novel introductions or exogenous perturbations than others. Explaining this relative is essential to understanding when and why new organizational forms appear, persist, and expand, both cognitively and geographically. We offer a comparative analysis of two cases of emergence in 19th-century New York City that examines the conditions under which a new organizational form - a research-intensive botanical garden - developed and took root. We show that social worlds are highly poised when environmental, intellectual, and civic factors have reinforcing consequences. Poisedness is amplified when the social character of the individuals produced by specific historical milieux attunes these innovators to the larger social and material processes that favor the creation of new modes of organization. Although our analysis of poisedness is fixed on a specific time and place, New York City over the course of the 19th century, our arguments about the emergence of new organizational forms apply readily to other settings and time periods.Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients.

Objective: Efavirenz (EFV) along with two nucleoside reverse transcriptase inhibitors (NRTIs) is a recommended initial antiretroviral regimen. Understanding characteristics related to EFV success is clinically useful.Design: Data from 2220 antiretroviral-naive participants randomized to EFV and two to three NRTIs in four ACTG trials as well as a long-term cohort were analysed.Methods: Logistic regression, using inverse probability of censoring weighting to address selective-follow-up bias, was used to identify factors associated with EFV success (no treatment interruptions of >30 days, HIV RNA<200 copies/ml) 1 year post initiation and at years 2-5 if successful at year 1.Results: Pretreatment characteristics were median age 38 years, 82% male, 40% white, 10% history of IDU (HxIDU), median CD4(+) T-lymphocyte 227 cells/mu l and 33% HIV RNA more than 100 000 copies/ml. In a multivariable model, factors associated with year 1 EFV success were race [white odds ratio (OR) 1.5; P<0.001; Hispanic OR 1.5; P=0.003 vs. black], no pretreatment sign/symptom grade 3 or higher (OR 1.7; P=0.008) and no HxIDU (OR 1.7; P=0.001). Predictors of EFV success at years 2-5 were no HxIDU (years 2-5; ORs 1.9-2.2); self-reported complete (4 days prior to study visit) adherence during year 1 (years 2-4; ORs 1.6-1.9); fewer missed visits during year 1 (years 2, 4, 5; ORs 0.92-0.98/1% increase); HIV RNA less than 50 copies/ml at year 1 (years 2, 3; ORs 1.9-2.2); and older age (>50 vs. <= 30 years) (years 2-4: ORs 2.3-3.7).Conclusion: Characteristics predictive of EFV success in the short-term and longer term differed except for HxIDU. Behaviours occurring during year 1 were associated with EFV success over 5 years. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

In the last decade, an increasing number of U.S. botanical gardens have adopted the concept of “sustainability” as an explicit element of their missions and practices. By reducing water, energy, and pesticide usage, these gardens seek to model environmental behavior that mitigates the destructive impact of human activities. However, botanical gardens are also complex organizations whose members have varying understandings of their organization’s identity. Through 52 interviews conducted at 10 botanical gardens, I examined the cognitive-cultural resources used by members as they explained new sustainability initiatives. I found that a key cognitive-cultural resource for respondents, overlooked in past studies of identity work, was an organization’s local setting, in both its “social” and “natural” aspects. I discuss the implications of this finding for organizational identity theory. I conclude by considering how this local setting can be mobilized in botanical gardens and other kinds of organizations trying to gain support for sustainability initiatives. I argue that the higher the salience of local natural settings for members, the more easily they can integrate environmental sustainability into their understanding of their organization’s identity.

Toll‐like receptors (TLRs) are transmembrane receptors that activate cells of the innate immune systems upon recognition of pathogen‐associated molecular patterns. The TLR4 is an essential component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on development of opportunistic diseases in HIV‐infected patients.

In The New Jim Crow, civil rights lawyer and Ohio State University law professor Michelle Alexander examines the legal and social framework that supports the regime of mass incarceration of black men in the United States. As Alexander carefully recounts, beginning in the early 1980s with President Reagan’s declaration of a ‘‘War on Drugs,’’ a number of policy initiatives, Supreme Court decisions, and vested interests, aided and abetted by political divisiveness and public apathy, coalesced to create the social, legal, and political environment that has supported mass incarceration ever since. Alexander’s analysis reveals disturbing parallels between the racial caste systems of slavery, Jim Crow, and today’s mass incarceration of black men in our country. In the end, however, Alexander shies away from proposing a potentially successful strategy for redressing the dilemma she so carefully depicts. Rather, she ‘‘punts,’’ or ‘‘cops out,’’ as we would have said in earlier eras. Alexander begins her analysis with a brief history of the several hundred years of variously oppressive race relations between whites and blacks in the United States. Quite correctly, Alexander observes that this history may be fruitfully understood as a sequence of renascent forms of social control refashioned to the new tenor of the times. Thus, Alexander traces the history of American political rhetoric in the latter half of the twentieth century where ‘‘law and order’’ comes to constitute code for ‘‘the race problem’’ and a policy of malign neglect toward African Americans is transmuted into an active political strategy devised to develop Republican political dominance in the southern states. Ultimately, as we know, the twin themes of crime and welfare propelled Ronald Reagan into the presidency. Searching for a follow-up initiative to define his early presidency, Reagan settled on increased attention to street crime, especially drug law enforcement. In short, the War on Drugs was not some disembodied social agenda, nor was it driven by public demand, as only two percent of Americans believed crime was an important issue at the time. Rather, as Alexander shows, the War on Drugs was a direct outgrowth of race-based politics and therefore the fact that it has had a disproportionate impact on young black men should come as no surprise. Alexander next turns her attention to the interwoven details of the social, legal, and political fabric that wrap the War on Drugs in supportive garb. As Alexander recites, the War on Drugs is the cornerstone on which the current regime of race-based mass incarceration rests because: (a) convictions for drug offenses are the single most important cause of the explosion in incarceration rates since 1980, and (b) black Americans are disproportionately arrested, convicted, and subjected to lengthy sentences for drug offenses when compared to white Americans, even though drug use rates among white Americans have been consistently shown to be higher than for black Americans. Thus, any practices or policies that support the execution of the War on Drugs support the continuation of our movement toward mass incarceration of an entire category of Americans. Among the many developments Alexander reviews, one may note: changes in Supreme Court doctrine with respect to police stops, warrantless searches, consent searches, and suspicionless police sweeps for drug activity; federal initiatives to offer grants to support narcotics task forces; the development and expansion of modern drug forfeiture laws which permitted state and local law enforcement agencies to keep the vast majority of seized cash and assets in drug raids; and the legislative enactment of mandatory minimum and ‘‘three strikes’’ sentencing schemes, and their ready

Heat shock protein 90 (Hsp90) accounts for 1-2% of the total proteins in normal cells and functions as a molecular chaperone that folds, assembles, and stabilizes client proteins. Hsp90 is over-expressed (3- to 6-fold increase) in stressed cells, including cancer cells, and regulates over 200 client and co-chaperone proteins. Hsp90 client proteins are involved in a plethora of cellular signaling events including numerous growth and apoptotic pathways. Since pathway-specific inhibitors can be problematic in drug-resistant cancers, shutting down multiple pathways at once is a promising approach when developing new therapeutics. Hsp90's ability to modulate many growth and signaling pathways simultaneously makes this protein an attractive target in the field of cancer therapeutics. Herein we present evidence that a small molecule modulates Hsp90 via binding between the N and middle domain and allosterically inhibiting the binding interaction between Hsp90 and four C-terminal binding client proteins: IP6K2, FKBP38, FKBP52, and HOP. These last three clients contain a tetratricopeptide-repeat (TPR) region, which is known to interact with the MEEVD sequence on the C-terminus of Hsp90. Thus, this small molecule modulates the activity between co-chaperones that contain TPR motifs and Hsp90's MEEVD region. This mechanism of action is unique from that of all Hsp90 inhibitors currently in clinical trials where these molecules have no effect on proteins that bind to the C-terminus of Hsp90. Further, our small molecule induces a Caspase-3 dependent apoptotic event. Thus, we describe the mechanism of a novel scaffold that is a useful tool for studying cell-signaling events that result when blocking the MEEVD-TPR interaction between Hsp90 and co-chaperone proteins.

Scholars have identified benefits of viewing work as a calling, but little research has explored the notion that people are frequently unable to work in occupations that answer their callings. To develop propositions on how individuals experience and pursue unanswered callings, we conducted a qualitative study based on interviews with 31 employees across a variety of occupations. We distinguish between two types of unanswered callings---missed callings and additional callings---and propose that individuals pursue these unanswered callings by employing five different techniques to craft their jobs (task emphasizing, job expanding, and role reframing) and their leisure time (vicarious experiencing and hobby participating). We also propose that individuals experience these techniques as facilitating the kinds of pleasant psychological states of enjoyment and meaning that they associate with pursuing their unanswered callings, but also as leading to unpleasant states of regret over forgone fulfillment of their unanswered callings and stress due to difficulties in pursuing their unanswered callings. These propositions have important implications for theory and future research on callings, job crafting, and self-regulation processes.

Heat shock proteins (HSP) are a family of highly conserved proteins, whose expression increases in response to stresses that may threaten cell survival. Over the past decade, heat shock protein 90 (Hsp90) has emerged as a potential therapeutic target for cancer as it plays a vital role in normal cell maturation and acts as a molecular chaperone for proper folding, assembly, and stabilization of many oncogenic proteins. To date, a majority of Hsp90 inhibitors that have been discovered are macrocycles. The relatively rigid conformation provided by the macrocyclic scaffold allows for a selective interaction with a biological target such as Hsp90. This review highlights the discovery and development of nine macrocycles that inhibit the function of Hsp90, detailing their potency and the client proteins affected by Hsp90 inhibition.

Utilizing the structure–activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.

Described is the SAR of 18 di-sansalvamide A derivatives and the mechanism of action of the most potent compound. We show that this scaffold is a promising lead in the development of novel cancer therapeutics because it is cytotoxic at nanomolar potency, inhibits a well-established oncogenic target (Hsp90), and does not share structural motifs with current drugs on the market.

We report an extensive structure-activity relationship (SAR) of 78 compounds active against two pancreatic cancer cell lines. Our comprehensive evaluation of these compounds utilizes SAR that allow us to evaluate which features of potent compounds play a key role in their cytotoxicity. This is the first report of 19 new second-generation structures, where these new compounds were designed from the first generation of 59 compounds. These 78 structures were tested for their cytotoxicity and this is the first report of their activity against two pancreatic cancer cell lines. Our results show that out of 78 compounds, three compounds are worth pursuing as leads, as they show potency of >= 55% in both cancer cell lines. These three compounds all have a common structural motif, two consecutive D-amino acids and an N-methyl moiety. Further, of these three compounds, two are second-generation structures, indicating that we can incorporate and utilize data from the first generation to design potency into the second generation. Finally, one analog is in the mid nanomolar range, and has the lowest IC50 of any reported San A derivative. These analogs share no structural homology to current pancreatic cancer drugs, and are cytotoxic at levels on par with existing drugs treating other cancers. Thus, we have established Sansalvamide A as an excellent lead for killing multiple pancreatic cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.

In 1980, a McKinsey consultant and former Environmental Protection Agency administrator named Bill Drayton founded Ashoka, an organization dedicated to fi nding and fostering what he called “social entrepreneurs.” “Social entrepreneurs,” says Ashoka’s Web site today, “are individuals with innovative solutions to society’s most pressing social problems. They are ambitious and persistent, tackling major social issues and offering new ideas for wide-scale change. Rather than leaving societal needs to the government or business sectors, social entrepreneurs fi nd what is not working and solve the problem by changing the system, spreading the solution, and persuading entire societies to take new leaps” (www.ashoka.org). Though debate continues among scholars and funders about how best to measure the impact of social entrepreneurship, Drayton’s efforts (and those of his emulators) have clearly contributed to a shift in the way many individuals and organizations now think about creating social change. Less than three decades after Drayton founded Ashoka, the terms “social entrepreneur” and “social entrepreneurship” are common parlance. Leading business schools now offer training for aspiring social entrepreneurs, and many undergraduates think of social entrepreneurship as a possible career choice.

Despite some promising steps in the right direction, organizational analysis has yet to exploit fully the theoretical and empirical possibilities inherent in the writings of Pierre Bourdieu. While certain concepts associated with his thought, such as field and capital, are already widely known in the organizational literature, the specific ways in which these terms are being used provide ample evidence that the full significance of his relational mode of thought has yet to be sufficiently apprehended. Moreover, the almost complete inattention to habitus, the third of Bourdieu’s major concepts, without which the concepts of field and capital (at least as he deployed them) make no sense, further attests to the misappropriation of his ideas and to the lack of appreciation of their potential usefulness. It is our aim in this paper, by contrast, to set forth a more informed and comprehensive account of what a relational – and, in particular, a Bourdieu-inspired – agenda for organizational research might look like. Accordingly, we examine the implications of his theoretical framework for interorganizational relations, as well as for organizations themselves analyzed as fields. The primary advantage of such an approach, we argue, is the central place accorded therein to the social conditions under which inter- and intraorganizational power relations are produced, reproduced, and contested.