The primary function of smooth muscle cells is to contract and alter the stiffness or diameter of hollow organs such as blood vessels, the airways and the gastrointestinal and urogenital tracts. In addition to purely structural functions, smooth muscle cells may play important metabolic roles, particularly in various inflammatory responses. In cell culture, these cells have been shown to be metabolically dynamic, synthesizing and secreting extracellular matrix proteins, glycosaminoglycans and a wide variety of cell–cell signaling proteins, such as interleukins, chemokines (...) and peptide growth factors. Secreted cell signaling proteins participate in the inflammatory response of smooth muscle‐containing organs, and some can also stimulate smooth muscle migration, proliferation and contraction. The cellular signaling pathways controlling synthesis of these signaling proteins are similar to those used by cells mediating innate immunity and may contribute to pathogenesis of diverse diseases including atherosclerosis, asthma, inflammatory bowel diseases and preterm labor. Appreciating the role of smooth muscle cells in these diseases may lead to better understanding of the beneficial effects of anti‐inflammatory drugs as well as identification of new targets for anti‐inflammatory therapy. BioEssays 26:646–655, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This book is for those who, like the astronauts, cannot look at this view of our planet without asking "WHY?" The search conducted within these pages is a logical journey into the fields of biology, psychology, physics, parapsychology, yogic science, and Eastern and Western religious philosophies. Are they merely viewing different aspects of the same Truth?

The literature of our day shows experimental scientists to be divided between two schools of thought, now generally called Mechanist and Vitalist. The literature of any day these last 2000 years would tell the same tale, but for occasional changes of name. Where an issue dividing scientists is seen to be an experimental issue, it presents no challenge to the philosopher. His interest is limited to the question, How shall we find out? and where all are agreed as to the (...) way of settling a difference of opinion, he can wait with patience to learn the result. But the very history of this world-old and world-wide conflict between schools of experimental science shows that it never has been, is not now, could never become one whose issue turned on the outcome of this or that experiment; nor in all the 2000 years the conflict has lasted, has science been able to come upon any other type of evidence by which the issue might be settled. As one of a class of similar issues, ancient, pervasive, persistent, the manner of whose decision lies still beyond the grasp of experimental science, this Mechanist-Vitalist controversy gives the philosopher much to think about. (shrink)

The cohesin complex is best known for its role in sister chromatid cohesion. Over the past few years, it has become apparent that cohesin also regulates gene expression, but the mechanisms by which it does so are unknown. Recently, three groups mapped numerous cohesin-binding sites in mammalian chromosomes and found substantial overlap with the CCCTC-binding factor (CTCF).1-3 CTCF is an insulator protein that blocks enhancer–promoter interactions, and the investigators found that cohesin also contributes to this activity. Thus, these studies demonstrate (...) at least one mechanism by which cohesin can control gene expression. BioEssays 30:715–718, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

1. Foreword. Man's every act is an act of faith; generally, an unconscious faith; seldom, an examined faith; never, a faith that by taking thought could have been replaced by assured certainties. All this appears whenever we stop to “rationalize” our conduct. Whatever that conduct may have been, it can be made to appear reasonable only if some propositions are taken to be true, others false. Or, perhaps the more experienced and less exacting mind would feel the reasonableness of its (...) actions to have been as well established as might be, if it could show the premises with which its acts were consistent to be more likely true than false; those with whose truth they were inconsistent, more likely false than true. Either way of putting it points to the one moral; namely, that, apart from incalculable chance, there is nothing but one's judgment in the matter of premises to determine all that one's life can come to know of fruition or frustration. Nothing, then, can be more important to any man than to do all he can to assure the soundness of his reasons for the faith that is in him; i.e. to test the weight of evidence supporting the working hypotheses on which he is willing to act. But to have considered the evidence for the hypotheses on which he has acted or is prepared to act, could be practically useful only to one who had in one way or another come by a sound idea of the evidence on which one should act, if one's actions are not to end in disappointment. The result at which a man's thought on this matter of evidence may have arrived, will constitute his theory of evidence; and the task of constructing the soundest possible theory of evidence is the undertaking of philosophy. (shrink)

4. The Mind's Lawmaking: Critical Idealism. Pleased with something dramatic in the phrase, we often characterize experiment as “a question put to Nature.” But if there be anything flattering to our state in Nature's submission to our questioning, there can be nothing grateful to our heart in her manner of answering. “Are we all to die?” Nature answers, “Yes.” “Will the sun that warmed our fathers last out our children?” Nature answers, “No.” Thus Nature giveth and Nature taketh away; her (...) complaisance ends with letting us know her way with us. (shrink)

During the course of the last century it has grown increasingly clear that not all the issues with which an experimental science can be faced are experimental issues. If there were no other ground for this belief, history itself would force upon us some such conviction. For there are differences of opinion dividing men today that have divided men from the earliest times recorded, and in every one of the ages in between the self-same issue will have involved in dissension, (...) not an occasional disputant here and there, but all the best thinkers in all the known sciences of their day. Yet at no time has either party to such strifes been in possession of facts ignored by the other; for had this been the case, the ignorant party must ere now have been driven from the field by force of the facts it ignored. It is fair to suppose that an issue which has come no nearer to solution as century after century added its contribution to the store of human knowledge, cannot depend for its decision on any information to be looked for from the centuries to come. (shrink)

Self-defining memories are touchstones in individuals’ narrative identity. This is the first SDM study to compare college students from the mainland People’s Republic of China to American college students. It examined SDMs, Big Five personality traits, and memory function in 60 students from each country. Participants rated their memories for affect, recall frequency, and importance. Chinese students recalled their most positively rated memories more frequently and with greater importance, while American students did not show this pattern. American students who scored (...) higher in Openness were more likely to recall negative memories. Memory content coding revealed that Chinese students recalled significantly more guilt/shame events than American students. Further analysis indicated that these memories were particularly focused on academic performance and parental expectations. The discussion suggests that follow-up studies look at differing emotion regulation strategies in the two countries, as well as at how the two different educational systems are affecting late adolescent identity formation processes. (shrink)

Following promulgation of the Nuremberg code in 1947, the ethics of research on human subjects has been a challenging and often contentious topic of debate. Escalation in the use of research participants in low-income countries over recent decades , has intensified the debate on the ethics of international research and led to increasing attention both to exploitation of vulnerable subjects and to considerations of how the 10:90 gap in health and medical research could be narrowed. In 2000, prompted by the (...) discussions over several years that led to the US NIH launching a capacity building programme on research ethics for members of research ethics committees in developing countries, we advanced a ‘new look’ for the ethics of international research.1 Since then progress has been made on several fronts.First, our ideas—considered somewhat radical and impractical at the time—have been provocatively addressed by scholars who have either contested them or advanced similar conceptions of what obligations international researchers have to research participants and communities in low income countries before, during and after clinical trials. Second, those researchers who have been sympathetic to our ideas have either endeavoured to put these into practice or have investigated the feasibility of doing so. Third, the intractability of the 10/90 gap and the escalation of interest in global health have sensitised many to the need to amplify the uptake of these ideas in practice.Here, we briefly review the conceptual and practical developments in international research ethics. While much conceptual progress has been made (and the concepts are now appearing …. (shrink)

Scientists engaged in global health research are increasingly faced with barriers to access and use of human tissues from the developing world communities where much of their research is targeted. In part, the problem can be traced to distrust of researchers from affluent countries, given the history of 'scientific-imperialism' and 'biocolonialism' reflected in past well publicized cases of exploitation of research participants from low to middle income countries. To a considerable extent, the failure to adequately engage host communities, the opacity (...) of informed consent, and the lack of fair benefit-sharing have played a significant role in eroding trust. These ethical considerations are central to biomedical research in low to middle income countries and failure to attend to them can inadvertently contribute to exploitation and erode trust. A 'tissue trust' may be a plausible means for enabling access to human tissues for research in a manner that is responsive to the ethical challenges considered. Preventing exploitation and restoring trust while simultaneously promoting global health research calls for innovative approaches to human tissues research. A tissue trust can reduce the risk of exploitation and promote host capacity as a key benefit. (shrink)

A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems.

A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems.

By combining and augmenting recent arguments that have appeared in the literature, I show how a modified Rawlsian theory of justice generates a strong environmental and animal rights ethic. These modifications include significant changes in the conditions of the contract situation vis-a-vis A Theory of Justice, but I argue that these modifications are in fact more consistent with Rawls’ basic assumptions about the functions of a veil of ignorance and a thin theory of the good.

The growth of global value chains (GVCs) and the emergence of novel forms of value chain governance pose two questions for normative business ethics. First, how should we conceptualize the relationships between members of a GVC? Second, what ethical implications follow from these relationships, both with respect to interactions between GVC members and with respect to achieving broader transnational governance goals? We address these questions by examining the emergence of transnational eco-labeling as an increasingly prominent form of GVC governance that (...) is redefining the relationship between nominally independent firms. On the first question, we argue that GVCs occupy a middle ground between intrafirm and interfirm transactions, thereby posing a challenge to theoretical frameworks that attempt to apply ethical standards based on transaction types. On the second question, we argue that this unique institutional status leads to a range of novel ethical considerations and dilemmas for GVC members. Lead firms, their suppliers, and third-party standard-setters all confront new ethical quandaries when third-party eco-labeling is introduced to a GVC. The nature of these quandaries means that, while GVCs may be well-positioned to serve as instruments of transnational governance, they are frequently not well-oriented to do so. Our analysis marks an initial attempt to map the ethical considerations that apply to members of a GVC, and in doing so, places the literature on normative business ethics and transnational governance in a closer conversation. (shrink)

The growth of global value chains (GVCs) and the emergence of novel forms of value chain governance pose two questions for normative business ethics. First, how should we conceptualize the relationships between members of a GVC? Second, what ethical implications follow from these relationships, both with respect to interactions between GVC members and with respect to achieving broader transnational governance goals? We address these questions by examining the emergence of transnational eco‐labeling as an increasingly prominent form of GVC governance that (...) is redefining the relationship between nominally independent firms. On the first question, we argue that GVCs occupy a middle ground between intrafirm and interfirm transactions, thereby posing a challenge to theoretical frameworks that attempt to apply ethical standards based on transaction types. On the second question, we argue that this unique institutional status leads to a range of novel ethical considerations and dilemmas for GVC members. Lead firms, their suppliers, and third‐party standard‐setters all confront new ethical quandaries when third‐party eco‐labeling is introduced to a GVC. The nature of these quandaries means that, while GVCs may be well‐positioned to serve as instruments of transnational governance, they are frequently not well‐oriented to do so. Our analysis marks an initial attempt to map the ethical considerations that apply to members of a GVC, and in doing so, places the literature on normative business ethics and transnational governance in a closer conversation. (shrink)

The justification for advance directives is grounded in the notion that they extend patient autonomy into future states of incompetency through patient participation in decision making about end-of-life care. Four objections challenge the necessity and sufficiency of individual autonomy, perceived to be a defining feature of liberal philosophical theory, as a basis of advance care planning. These objections are that the liberal concept of autonomy (i) implies a misconception of the individual self, (ii) entails the denial of values of social (...) justice, (iii) does not account for justifiable acts of paternalism, and (iv) does not account for the importance of personal relationships in the advance care planning process. The last objection is especially pertinent in light of recent empirical research highlighting the importance of personal relationships in advance care planning. This article examines these four objections to autonomy, and the liberal theoretical framework with which it is associated, in order to re-evaluate the philosophical basis of advance care planning. We argue that liberal autonomy (i) is not a misconceived concept as critics assume, (ii) does not entail the denial of values of social justice, (iii) can account for justifiable acts of paternalism, though it (iv) is not the best account of the value of personal relationships that arise in advance care planning. In conclusion, we suggest that liberalism is a necessary component of a theoretical framework for advance care planning but that it needs to be supplemented with theories that focus explicitly on the significance of personal relationships. (shrink)

Medicine and health care generate many bioethical problems and dilemmas that are of great academic, professional and public interest. This comprehensive resource is designed as a succinct yet authoritative text and reference for clinicians, bioethicists, and advanced students seeking a better understanding of ethics problems in the clinical setting. Each chapter illustrates an ethical problem that might be encountered in everyday practice; defines the concepts at issue; examines their implications from the perspectives of ethics, law and policy; and then provides (...) a practical resolution. There are 10 key sections presenting the most vital topics and clinically relevant areas of modern bioethics. International, interdisciplinary authorship and cross-cultural orientation ensure suitability for a worldwide audience. This book will assist all clinicians in making well-reasoned and defensible decisions by developing their awareness of ethical considerations and teaching the analytical skills to deal with them effectively. (shrink)

:Corporations cannot exist, scholars rightly note, without being constituted by government. However, many take a further step, claiming that corporations are normatively distinct from other market actors because of this governmental provenance. They are mistaken. Like corporations, markets and contracts also require government for their creation. Governmental provenance does not distinguish corporations normatively because our coercive social institutions are pro tanto justified in re-arranging both corporate and non-corporate market activities on behalf of social and political values. The corporation is distinct (...) only practically and prudentially, in that it represents a more proximate instrument for effecting morality in the economy. (shrink)

This book is a volume in the Penn Press Anniversary Collection. To mark its 125th anniversary in 2015, the University of Pennsylvania Press rereleased more than 1,100 titles from Penn Press's distinguished backlist from 1899-1999 that had fallen out of print. Spanning an entire century, the Anniversary Collection offers peer-reviewed scholarship in a wide range of subject areas.

The Toronto experience suggests that there may be several general lessons for academic health sciences complexes to learn from the Olivieri/Apotex affair regarding the ethics, independence, and integrity of clinical research sponsored by for profit enterprises. From a local perspective, the OAA occurred when there already was a focus on the complex and changing relationships among the University of Toronto, its medical school, the fully affiliated teaching hospitals, and off campus faculty because of intertwined interests and responsibilities. The OAA became (...) a catalyst that accelerated various systemic reforms, particularly concerning academic/industry relations. In this article, the evolving governance framework for the Toronto academic health sciences complex is reviewed and these policy and process reforms discussed. These reforms have created collaborative activity among research ethics boards and contract research offices of the partner institutions, and allowed the joint university/hospital ethics centre to play a role in governance and policy, while respecting the missions and mandates of the involved institutions. Although few of the policies are dramatically innovative, what is arguably novel is the elaboration of an overarching governance framework that aims to move ethics to a central focus in the academic complex. Time alone will tell how sustainable and effective these changes are. (shrink)

The fear that business corporations have claimed unwarranted constitutional protections which have entrenched corporate power has produced a broad social movement demanding that constitutional rights be restricted to human beings and corporate personhood be abolished. We develop a critique of these proposals organized around the three salient rationales we identify in the accompanying narrative, which we argue reflect a narrow focus on large business corporations, a misunderstanding of the legal concept of personhood, and a failure to distinguish different kinds of (...) constitutional rights and the reasons for assigning them. Corporate personhood and corporate constitutional rights are not problematic per se once these notions are decoupled from biological, metaphysical, or moral considerations. The real challenge is that we need a principled way of thinking about the priority of human over corporate persons which does not reduce the efficacy of corporate institutions or harm liberal democracies. (shrink)