Cadherin‐mediated cell‐cell adhesion is perturbed in protein tyrosine kinase (PTK)‐transformed cells. While cadherins themselves appear to be poor PTK substrates, their cytoplasmic binding partners, the Arm catenins, are excellent PTK substrates and therefore good candidates for mediating PTK‐induced changes in cadherin behavior. These proteins, p120ctn, β‐catenin and plakoglobin, bind to the cytoplasmic region of classical cadherins and function to modulate adhesion and/or bridge cadherins to the actin cytoskeleton. In addition, as demonstrated recently for β‐catenin, these proteins also have crucial signaling (...) roles that may or may not be related to their effects on cell‐cell adhesion. Tyrosine phosphorylation of cadherin complexes is well documented and widely believed to modulate cell adhesiveness. The data to date, however, is largely correlative and the mechanism of action remains unresolved. In this review, we discuss the current literature and suggest models whereby tyrosine phosphorylation of Arm catenins contribute to regulation or perturbation of cadherin function. (shrink)

Over the past 50 years, academic-industrial collaborations and technology transfer have played an increasingly prominent role in the biomedical sciences. These relationships can speed the delivery of innovative drugs and medical technologies to clinical practice, creating important public health benefits as well as income for universities and their faculty. At the same time, they raise ethical concerns, particularly when research involves human subjects in clinical trials. Lapses in oversight of industry sponsored clinical trials at universities, and especially patient deaths in (...) a number of trials, have brought these issues into the public spotlight and have led the federal government to intensify its oversight of clinical research. The leadership of Harvard Medical School convened a group of leaders in academic medicine to formulate guidelines on individual financial conflicts of interest. They and other groups are working to formulate a national consensus on this issue. (shrink)

Stronach and Allan state that the use of humor by the disabled is an attempt to reintegrate themselves back into a social surround. Seeing this assignment of a reintegration function as a bit too teleological, and given the absence of interactional data, the reviewer is critical of the authors' reliance on literary research and offers an alternative way to study humor in interaction.

There are many similarities between the Christian concept of the Seven Deadly Sins, the Stoic concept of internal events, the Hebrew concept of 'awon (sin, punishment), and the existential concept of bad faith. All of these evidence a concern for an internalization of sin or bad faith, which is more common in Eastern than Western religions. These four views are contrasted with the English concept synne which represents the Western extemalization of sin or bad faith. This existential interpretation includes an (...) exploration of 'awon in the Cain and Abel story as well as several reflections concerning the difference between bad faith and good faith. (shrink)

The literature on ethical decision-making is rooted in a cognitive perspective that emphasizes the role of moral judgment. Recent research in interpersonal dynamics, however, has suggested that ethics revolves around an individual’s perceptions and views of others. We draw from both literatures to propose and empirically examine a contingent model. We theorize that whether the individual relies on cognitions about the ethical issue or perceptions of others depends on the level of social consensus surrounding the issue. We test our hypotheses (...) in three studies. Results suggest that not only does social consensus determine whether an individual relies on ethical cognitions about the issue or perceptions of others, but also that an individual’s view of self is an important moderator in these relationships. We conclude by considering implications of this research for theory and practice. (shrink)

Abstract:Therapeutic misconception (TM)—when clinical research participants fail to adequately grasp the difference between participating in a clinical trial and receiving ordinary clinical care—has long been recognized as a significant problem in consent to clinical trials. We suggest that TM does not primarily reflect inadequate disclosure or participants’ incompetence. Instead, TM arises from divergent primary cognitive frames. The researchers’ frame places the clinical trial in the context of scientific designs for assessing intervention efficacy. In contrast, most participants have a cognitive frame (...) that is personal and focused primarily on their medical problems. To illustrate this, we draw on interview material from both clinical researchers and participants in clinical trials. We suggest that reducing TM requires encouraging subjects to adjust their frame, not just add information to their existing frame. What is necessary is ascientific reframingof participation in a clinical trial. (shrink)

For the first time in three centuries, this book brings back into print three discourses now confirmed to have been written by the young Thomas Hobbes. Their contents may well lead to a resolution of the long-standing controversy surrounding Hobbes's early influences and the subsequent development of his thought. The volume begins with the recent history of the discourses, first published as part of the anonymous seventeenth-century work, _Horae Subsecivae_. Drawing upon both internal evidence and external confirmation afforded by new (...) statistical "wordprinting" techniques, the editors present a compelling case for Hobbes's authorship. Saxonhouse and Reynolds present the complete texts of the discourse with full annotations and modernized spellings. These are followed by a lengthy essay analyzing the pieces' significance for Hobbes's intellectual development and modern political thought more generally. The discourses provide the strongest evidence to date for the profound influences of Bacon and Machiavelli on the young Hobbes, and they add a new dimension to the much-debated impact of the scientific method on his thought. The book also contains both introductory and in-depth explanations of statistical "wordprinting.". (shrink)

For the first time in three centuries, this book brings back into print three discourses now confirmed to have been written by the young Thomas Hobbes. Their contents may well lead to a resolution of the long-standing controversy surrounding Hobbes's early influences and the subsequent development of his thought. The volume begins with the recent history of the discourses, first published as part of the anonymous seventeenth-century work, _Horae Subsecivae_. Drawing upon both internal evidence and external confirmation afforded by new (...) statistical "wordprinting" techniques, the editors present a compelling case for Hobbes's authorship. Saxonhouse and Reynolds present the complete texts of the discourse with full annotations and modernized spellings. These are followed by a lengthy essay analyzing the pieces' significance for Hobbes's intellectual development and modern political thought more generally. The discourses provide the strongest evidence to date for the profound influences of Bacon and Machiavelli on the young Hobbes, and they add a new dimension to the much-debated impact of the scientific method on his thought. The book also contains both introductory and in-depth explanations of statistical "wordprinting.". (shrink)

Entrepreneurs generally lack the marketing capabilities necessary to bring their new product to market. To engage the resources required to do this, they must somehow place a value on the enterprise. However, all of the methods of valuation currently available are based on the use of historical or current revenues, and therefore are not applicable to an entrepreneurial enterprise with a first-time product. In Valuing an Entrepreneurial Enterprise, Audretsch and Link present a valuation method uniquely tailored to emerging technology-based ventures (...) that have no revenue history to lean on. Unlike many traditional methods, theirs does not take into account the track record of companies and products similar to that being valuated. Instead, it draws on economic theory to formulate a solution to the problem. The book develops conceptual ground, including trends in entrepreneurship, models of innovation, and the economics of standards and entrepreneurship policy. The authors review the traditional valuation methods and illustrate them numerically with case studies to show how the traditional approach produces an incorrect valuation. The core of the book presents the new methodology and demonstrates how it avoids the pitfalls of past approaches. The authors also show how public policy on technology and infrastructure changes valuations of start-up firms in areas such as stem-cell products and renewable fuels projects. Valuing an Entrepreneurial Enterprise will serve as a valuable resource for advanced students, economists, financial planners, and valuators interested in new valuation methods and the theory behind them, as well as those interested in entrepreneurship. (shrink)

The paper borrows from recent work by classicists on satyr play and demonstrates significant parallels between Plato’s Republic and the structure, theme and stereotypical contents that characterize this newly studied genre of ancient Greek drama. Like satyr play, the Republic includes repeated passages where metatheatricality can reverse the meaning. The frequent occurrence of all the stereotypical elements of satyr play in Plato’s Republic also suggests to readers that they should be responding to Socrates’ narration as they would to a satyr (...) play, again reversing meaning by communicating a set of literary expectations to Plato’s readers over the heads of Socrates’ interlocutors. As is frequently the case with satyr play, the political purpose of the drama is the critique of tyrannical government. The need for a systematically ironic interpretation of the dialogue is raised. (shrink)

Although the concept of Rule of Law has been revived and developed vigorously by mid‐twentieth century conservative political theorists, contemporary legal positivists have not been impressed. The author reviews this confrontation, outlines the logic for a strong theory of Rule of Law, and surveys the leading attempts to provide compelling grounds for such a theory.

The widely recognized impasse in legal theory, which requires an account of law as “both a social fact and a framework of reasons for action” has been most interestingly addressed in recent years by writers characterizing law as convention in the sense of a solution to a game theoretical “coordination problem.” As critics have neutralized most of these proposals, the author advances an account of conventionalism, drawing on economic and sociological theory, which he claims makes the bridge between positivist and (...) naturalist theories of law without compromising the basic insights of either. The result is a unified theory of law, politics and society. (shrink)