Coiled‐coils are found in proteins throughout all three kingdoms of life. Coiled‐coil domains of some proteins are almost invariant in sequence and length, betraying a structural and functional role for amino acids along the entire length of the coiled‐coil. Other coiled‐coils are divergent in sequence, but conserved in length, thereby functioning as molecular spacers. In this capacity, coiled‐coil proteins influence the architecture of organelles such as centrioles and the Golgi, as well as permit the tethering of transport vesicles. Specialized coiled‐coils, (...) such as those found in motor proteins, are capable of propagating conformational changes along their length that regulate cargo binding and motor processivity. Coiled‐coil domains have also been identified in enzymes, where they function as molecular rulers, positioning catalytic activities at fixed distances. Finally, while coiled‐coils have been extensively discussed for their potential to nucleate and scaffold large macromolecular complexes, structural evidence to substantiate this claim is relatively scarce. (shrink)

The recent discovery and structure determination of a novel ubiquitin‐like dimerization domain in protein kinase D (PKD) has significant implications for its activation. PKD is a serine/threonine kinase activated by the lipid second messenger diacylglycerol (DAG). It is an essential and highly conserved protein that is implicated in plasma membrane directed trafficking processes from the trans‐Golgi network. However, many open questions surround its mechanism of activation, its localization, and its role in the biogenesis of cargo transport carriers. In reviewing this (...) field, the focus is primarily on the mechanisms that control the activation of PKD at precise locations in the cell. In light of the new structural findings, the understanding of the mechanisms underlying PKD activation is critically evaluated, with particular emphasis on the role of dimerization in PKD autophosphorylation, and the provenance and recognition of the DAG that activates PKD. (shrink)

Witness to the Fire: Creativity and the Veil of Addiction. Linda Schierse Leonard. Boston: Shambhala Publications, 1989. ISBN 0‐87773‐393‐7. Cloth $19.95. Pp. xviii. 390.

Thought-intrusions, automatic inferences, and other unintended thought are beginning to play an important role in the study of psychiatric disease as well as normal thought processes. We examine one method for study of task-unrelated imagery and thought . TUIT likelihood was shown to be reliably measured over a wide range of vigilance tasks, to have high short-term and long-term test-retest reliability, and to be sensitive to information processing demands. Likelihood of TUITs was shown to be different as a function of (...) aging, hyperactivity, time of day, and level of depression. Thus, we now can reliably measure the influence of endogenous and exogenous influences on TUITs. In addition, TUIT measurement was proposed as a minimally interfering and natural second task for determining resource utilization in a primary task. Finally, this method was offered as a reliable approach to quantification of such mental states as obsessions and drug craving and addiction. (shrink)

One well-known objection to supersubstantivalism is that it is inconsistent with the contingency of location. This paper presents a new objection to supersubstantivalism: it is inconsistent with the vagueness of location. Though contingency and vagueness are formally similar, there are important philosophical differences between the two. As a result, the objection from vague location will be structurally different than the objection from contingent location. The paper explores these differences and then defends the argument that supersubstantivalism is inconsistent with the plausible (...) thesis that it is vague where I am located. (shrink)

This book explores how the trans phenomenon can challenge the existing concept of the Self and its nature. The catalyst is Moore’s Paradox: can a trans person coherently state ‘I am a girl but I don’t believe that’? More deeply, three fundamental philosophical questions arise, of ontological, epistemological, and conceptual significance: what Self understands that the natal-gender is ‘wrong’? How does the trans person know that the natal-gender is ‘wrong’ and what counts as evidence? And finally, how does this effect (...) the concept of Self itself? Seeking answers, Brakel considers various theories of the Self, including classical accounts, modern views, and models developed by selected gender theorists. The book then takes a biological turn, first developing an evolutionary proper-function analysis of gender and trans-gender and subsequently proposing the possibility of a new ontological phenotype. With a review of cutting-edge neuroscientific research conducted over the last twenty-five years, Brakel propels this timely and important investigation toward the future, using experimental philosophy empirical studies adapted from classic thought experiments on the nature of the Self. (shrink)

From the ethics perspective, “duty of care” is a difficult and contested term, fraught with misconceptions and apparent misappropriations. However, it is a term that clinicians use frequently as they navigate COVID-19, somehow core to their understanding of themselves and their obligations, but with uncertainty as to how to translate or operationalize this in the context of a pandemic. This paper explores the “duty of care” from a legal perspective, distinguishes it from broader notions of duty on professional and personal (...) levels, and proposes a working taxonomy for practitioners to better understand the concept of “duty” in their response to COVID-19. (shrink)

This is a unique, groundbreaking collection of autobiographical essays by leading women in philosophy. It provides a glimpse at the experiences of the generation that witnessed, and helped create, the remarkable advances now evident for women in the field.

While pharmaceutical industry involvement in producing, interpreting, and regulating medical knowledge and practice is widely accepted and believed to promote medical innovation, industry-favouring biases may result in prioritizing corporate profit above public health. Using diabetes as our example, we review successive changes over forty years in screening, diagnosis, and treatment guidelines for type 2 diabetes and prediabetes, which have dramatically expanded the population prescribed diabetes drugs, generating a billion-dollar market. We argue that these guideline recommendations have emerged under pervasive industry (...) influence and persisted, despite weak evidence for their health benefits and indications of serious adverse effects associated with many of the drugs they recommend. We consider pharmaceutical industry conflicts of interest in some of the research and publications supporting these revisions, and in related standard-setting committees and oversight panels. We raise concern over the long-term impact of these multifaceted involvements. Rather than accept industry conflicts of interest as normal, needing only to be monitored and managed, we suggest challenging that normalcy, and ask: what are the real costs of tolerating such industry participation? We urge the development of a broader focus to fully understand and curtail the systemic nature of industry’s influence over medical knowledge and practice. (shrink)

The traditional Western understanding of life and death as a strict dichotomy is challenged by a more descriptively accurate model of life's progressive cessation. Dying can be defined by a bounded zone of residual states of life that fits better with moral intuition and more sensitively guides action toward the dying.

This article describes the work of negotiating and reinterpreting "standard" protocols and criteria at the level of local practice, using the example of the procurement of human cadaver organs for transplantation. The tension between efforts to starulardize and globalize biomedical science, on the one hand, and fitting these efforts into everyday practices and understandings of practitioners, on the other, results in new constructions of medical knowledge about bodies and persons.

The meaning of dignity in health care has been primarily explored using interviews and surveys with various patient groups, as well as with health care practitioners. Philosophical analysis of dignity is largely avoided, as the existing philosophical literature is complex, multifaceted and of unclear relevance to health care settings. The aim of this paper is to develop a straightforward philosophical concept of dignity which is then applied to existing qualitative research. In health care settings, a patient has dignity when he (...) or she is able to live in accordance with his or her standards and values. Accordingly, health care practitioners respect a patient's dignity when they refrain from transgressing the patient's standards and values, or refrain from forcing the patient to transgress his or her standards and values. This concept is shown to explain and illuminate most of the key qualitative findings. It therefore provides a more coherent and synthesised concept of dignity in health care. (shrink)

Can Rawlsian public reason sufficiently justify public policies that regulate or restrain controversial medical and technological interventions in bioethics (and the broader social world), such as abortion, physician aid-in-dying, CRISPER-cas9 gene editing of embryos, surrogate mothers, pre-implantation genetic diagnosis of eight-cell embryos, and so on? The first part of this essay briefly explicates the central concepts that define Rawlsian political liberalism. The latter half of this essay then demonstrates how a commitment to Rawlsian public reason can ameliorate (not completely resolve) (...) many of the policy disagreements related to bioethically controversial medical interventions today. The goal of public reason is to reduce the size of the disagreement by eliminating features of the disagreement that violate the norms of public reason. The norms of public reason are those norms that are politically necessary to preserve the liberal, pluralistic, democratic character of this society. What remains is reasonable disagreement to be addressed through normal democratic deliberative processes. Specific issues addressed from a public reason perspective include personal responsibility for excessive health costs, the utility of a metaphysical definition of death for organ transplantation, and the moral status of excess embryos generated through IVF and/or their use in medical research. (shrink)

History and chronicle, by B. Croce.--History as a system, by J. Ortega y Gasset.--The idea of history, by R. G. Collingwood.--The historian's purpose; history and metahistory, by A. Bullock.--What are historians trying to do? By H. Pirenne.--What are historical facts? By C. Becker.--The concept of scientific history, by I. Berlin.--Reason in history, by G. W. F. Hegel.--The hedgehog and the fox, by I. Berlin.--What is history? By E. H. Carr.--Faith and history, by R. Niebuhr.--The world and the west, by A. (...) Toynbee.--Debates with historians, by P. Geyl.--Has history any meaning? By K. R. Popper.--Historical inevitability, by I. Berlin.--On fortune and misfortune in history, by J. Burckhardt.--Selected readings (p. 179-181). (shrink)

This article reports on an inquiry that investigated the development of ba constructions in early childhood Mandarin. All cases of ba construction were extracted from the Early Childhood Mandarin Corpus collected from 168 preschoolers aged 2;6, 3;6, 4;6, and 5;6. Early Childhood Mandarin Corpus, University of Hong Kong. Data analysis indicated that: Mandarin-speaking children produced a repertoire of 11 types of ba construction, and the children in the youngest age group were able to produce six types of them; children at (...) 4 years old experienced a critical developmental period of pragmatic use, and at 5 years old they had attained cognitive and linguistic maturity in understanding the semantic and syntactic features of ba constructions; and there was a significant age effect on the production of three types of ba construction, but no significant association between the children’s gender and their production of ba constructions. These findings offer fresh insights into understanding Chinese children’s innate capacity to understand the co-occurrence constraints concerning the syntactic, semantic and verb features inherent in ba construction, and their developmental ability to denote telic events by resorting to the appropriate ba sentence patterns. (shrink)

The statistical interpretation introduced by Born in mid-1926 is not the interpretation now associated with his name. Born's own understanding of that interpretation is revealed by looking at some of its roots in Born's earlier work with Franck on collisions, his collaboration with Jordan on that topic, his contributions to matrix mechanics, his attempt in collaboration with Wiener at an operator formulation of quantum mechanics, and at the exposition of the interpretation in Born's first papers on a wave mechanical treatment (...) of collisions. (shrink)

Abstract:Because the demand for intensive care unit (ICU) beds exceeds the supply in general, and because of the formidable costs of that level of care, clinicians face ethical issues when rationing this kind of care not only at the point of admission to the ICU, but also after the fact. Under what conditions—if any—may patients be denied admission to the ICU or removed after admission? One professional medical group has defended a rule of “first come, first served” in ICU admissions, (...) and this approach has numerous moral considerations in its favor. We show, however, that admission to the ICU is not in and of itself guaranteed; we also show that as a matter of principle, it can be morally permissible to remove certain patients from the ICU, contrary to the idea that because they were admitted first, they are entitled to stay indefinitely through the point of recovery, death, or voluntary withdrawal. What remains necessary to help guide these kinds of decisions is the articulation of clear standards for discontinuing intensive care, and the articulation of these standards in a way consistent with not only fiduciary and legal duties that attach to clinical care but also with democratic decision making processes. (shrink)

This paper challenges one line of argument which has been advanced to justify imposing risks of collateral harm on prospective beneficiaries of armed humanitarian interventions. This argument - the ‘Beneficiary Principle’ - holds that non-liable individuals’ immunity to being harmed as a side effect of just armed humanitarian interventions may be diminished by their prospects of benefiting from the intervention. Against this, I defend the view that beneficiary status does not morally distinguish beneficiaries from other non-liable individuals in such a (...) way as to permit exposing them to greater risks of being harmed. The argument proceeds in four steps. I first show that the BP can neither be grounded in liability-based nor in lesser-evil justifications for harming. I then argue that a standalone justification for unintended harming based on beneficiary status would face at least two critical challenges. The first concerns the BP’s applicability to collectives; the second questions the normative weight we can plausibly ascribe to beneficiary status when beneficiaries are such by virtue of being victims of wrongful threats of harm. I argue that standing to benefit is morally irrelevant when the benefit consists in the mitigation or prevention of wrongful harms, and consequently suggest that the BP may only serve as a distributive principle in allocating risks of harm if it is disambiguated in a number of critical aspects and applied in a more narrowlydefined set of circumstances. (shrink)

The phrase "personalized medicine" has a built-in positive spin. Simple genetic tests can sometimes predict whether a particular individual will have a positive response to a particular drug or, alternatively, suffer costly and debilitating side effects. But little attention has been given to some challenging issues of justice raised by personalized medicine. How should we determine who would have a just claim to access particular treatments, especially very expensive ones? How effective do those treatments need to be?If there were a (...) thick, bright line separating minimal responders from maximal responders, then we could allocate these treatments in a fair and cost-effective way. But there is no bright line. The .. (shrink)

In this paper, I present and defend a novel version of the Reactive Attitude account of moral blameworthiness. In Section 1, I introduce the Reactive Attitude account and outline Allan Gibbard's version of it. In Section 2, I present the Wrong Kind of Reasons Problem, which has been at the heart of much recent discussion about the nature of value, and explain why a reformulation of it causes serious problems for versions of the Reactive Attitude account such as Gibbard's. In (...) Section 3, I consider some ways in which Gibbard might attempt to avoid the Wrong Kind of Reason Problem. I argue that all of these ways fail to achieve their aim and further contend that the Wrong Kind of Reason Problem cannot be solved in a sufficiently convincing manner by the widely used method of making ad hoc distinctions among kinds of properties, kinds of attitudes, and kinds of reasons. In Section 4, I sketch my own version of the Reactive Attitude account of moral blameworthiness and show that it simply avoids the Wrong Kind of Reason Problem rather than attempting to solve the problem on a piecemeal basis. (shrink)

In this paper, I argue for the following points. First, all of us have a presumptive moral obligation to be organ donors if we are in the relevant medical circumstances at the time of death. Second, family members should not have the right to interfere with the fulfillment of that obligation. Third, the ethical basis for that obligation is reciprocity. If we want a sufficient number of organs available for transplantation, then all must be willing donors. Fourth, that likelihood is (...) diminished if individuals are entirely free to refuse to be organ donors but still would demand to be organ recipients. Fifth, although individuals would be ethically obligated to be organ donors, we still need to permit them to refuse to be organ donors. Sixth, to encourage individuals to stay within the organ donation system, we should have as a just and ethically justified policy denying individuals an organ transplant in the relevant medical circumstances if they have chosen to exit the organ donation system. Individuals would not be permitted to be organ recipients if they were unwilling to be organ donors. This is what it means to be part of what Rawls in Political liberalism (15-22) would refer to as a “fair system of social cooperation.” We refer to this as the “reciprocity requirement.”. (shrink)

This chapter is an investigation of the morality of medical deportation, the practice of returning undocumented migrants, despite their ill health and/or injuries, to their countries of origin. In Sect. 16.1, I look more closely at the nature of medical deportation. In Sect. 16.2, I argue that understanding the morality of medical deportation requires nonideal theory. In Sect. 16.3, I outline contractualism as a nonideal theory. In Sect. 16.4, I apply contractualism to medical deportation and make the case that, first, (...) there are in principle some cases in which medical deportation is morally permissible but, second, the standards that must be met in cases of morally permissible medical deportation are very high. In Sect. 16.5, I consider stakeholders other than the patient and the medical care facility and examine the ways in which effects on them might render medical deportation morally impermissible. I conclude that real-world cases of morally permissible medical deportation are rare at best, and there is little prospect of this situation changing. (shrink)

I begin this paper by discussing the difference between outweighing and canceling in conflicts of normativity. I then introduce a thought experiment that I call Crash Drive,and I use it to explain the nature of a certain kind of moral conflict as well as the appropriate emotional response – regret – on the part of the primary agent in this case. Having done this, I turn to a line of criticism opened by Bernard Williams and recently expanded by Jonathan Dancy (...) according to which archetypal examples of modern moral philosophies such as Kantianism cannot make sense of conflict and regret. Finally, I examine the general structure of such theories and explain how at least some of them can avoid this line of criticism. (shrink)

Enrique Dussel's writings span the theology of liberation, critiques of discourse ethics, evaluations of Marx, Levinas, Habermas, and others, but most importantly, the development of a philosophy written from the underside of Eurocentric modernist teleologies, an ethics of the impoverished, and the articulation of a unique Latin American theoretical perspective. This anthology of original articles by U.S. philosophers elucidating Dussel's thought, offers critical analyses from a variety of perspectives, including feminist ones. Also included is an essay by Dussel that responds (...) to these essays. (shrink)

Ethics, Policy & Environment, Volume 15, Issue 2, Page 241-243, June 2012.

Originally published: New York: Grossman Publishers, 1969.

Recently, there has been renewed interest in the search for low-mass magnetic monopoles. At the University of Oklahoma we are performing an experiment (Fermilab E882) using material from the old D0 and CDF detectors to set limits on the existence of Dirac monopoles of masses of the order of 500 GeV. To set such limits, estimates must be made of the production rate of such monopoles at the Tevatron collider, and of the binding strength of any such produced monopoles to (...) matter. Here we sketch the still primitive theory of such interactions, and indicate why we believe a credible limit may still be obtained. On the other hand, there have been proposals that the classic Euler–Heisenberg Lagrangian together with duality could be employed to set limits on magnetic monopoles having masses less than 1 TeV, based on virtual, rather than real processes. The D0 collaboration at Fermilab has used such a proposal to set mass limits based on the nonobservation of pairs of photons each with high transverse momentum. We critique the underlying theory, by showing that the cross section violates unitarity at the quoted limits and is unstable with respect to radiative corrections. We therefore believe that no significant limit can be obtained from the current experiments, based on virtual monopole processes. (shrink)

An appeal to all that doubt or disbelieve the truths of the Gospel, whether they be deists, Arians, Socinians, or nominal Christians, by W. Law.--Siris; a chain of philosophical reflexions and inquiries concerning the virtues of tar water, and divers other subjects, by G. Berkeley.--Observations on man, his frame, his duty, and his expectations, by D. Hartley.--The theory of moral sentiments, by A. Smith.--An essay on original genius, by W. Duff.--The light of nature pursued, by A. Tucker.--A new system; or, (...) An analysis of antient mythology, by J. Bryant.--Enquiry concerning political justice and its influence on morals and happiness, by W. Godwin. (shrink)