Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B‐chain helix interactions with the leucine‐rich repeat domain and A‐chain residue interactions with peptide loops from another part of the receptor, are also (...) seen in models of relaxin and insulin‐like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schäffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand‐induced activation of the IR and highlights the key issues that remain to be addressed. (shrink)

Unraveling the molecular detail of insulin receptor activation has proved challenging, but a major advance is the recent determination of crystallographic structures of insulin in complex with its primary binding site on the receptor. The current model for insulin receptor activation is that two distinct surfaces of insulin monomer engage sequentially with two distinct binding sites on the extracellular surface of the insulin receptor, which is itself a disulfide‐linked (αβ)2 homodimer. In the process, conformational changes occur both within the hormone (...) and the receptor, the latter resulting in the disruption of the intracellular interactions that hold the kinase domains in their basal state and in the initiation of the phosphorylation events that drive insulin signaling. The purpose of this paper is to summarize the extant structural data relating to hormone binding and how it effects receptor activation, as well as to discuss the issues that remain unresolved. (shrink)

The report of the President's Council on Bioethics, Human Cloning and Human Dignity, addresses the central ethical, political, and policy issue in human embryonic stem cell research: the moral status of extracorporeal human embryos. The Council members were in sharp disagreement on this issue and essentially failed to adequately engage and respectfully acknowledge each others' deepest moral concerns, despite their stated commitment to do so. This essay provides a detailed critique of the two extreme views on the Council (i.e., embryos (...) have full moral status or they have none at all) and then gives theoretical grounding for our judgment about the intermediate moral status of embryos. It also supplies an account of how to address profound moral disagreements in the public arena, especially by way of constructing a middle ground that deliberately pays sincere respect to the views of those with whom it has deep disagreements. (shrink)

Management theory and practice are facing unprecedented challenges. The lack of sustainability, the increasing inequity, and the continuous decline in societal trust pose a threat to ‘business as usual’. Capitalism is at a crossroad and scholars, practitioners, and policy makers are called to rethink business strategy in light of major external changes. In the following, we review an alternative view of human beings that is based on a renewed Darwinian theory developed by Lawrence and Nohria. We label this alternative (...) view ‘humanistic’ and draw distinctions to current ‘economistic’ conceptions. We then develop the consequences that this humanistic view has for business organizations, examining business strategy, governance structures, leadership forms, and organizational culture. Afterward, we outline the influences of humanism on management in the past and the present, and suggest options for humanism to shape the future of management. In this manner, we will contribute to the discussion of alternative management paradigms that help solve the current crises. (shrink)

In our paper we attempt an examination of Hume's positive contributions to the problem of personal identity. In contrast to Penelhum, smith and others, we argue that Hume can and does make sense of the identity of persons through time, but that this identity is not perfect in nature. We argue that Hume presents a logical construction theory of the self. We explain how such a view accounts for our identity and individuality and why it conforms to the empiricist approach.

The global array might prove to be an important and even necessary concept for explaining some multi-modal phenomena from the specificational perspective. However, we suspect that specification exists in energy arrays detectable by single or multiple sensory systems. We argue for a more general modality-neutral perspective and review results from recent research on audiovisual speech perception.

The Healer's Art curriculum is one of the best-known educational strategies to support medical student professional identity formation. HART has been widely used as an elective curriculum. We evaluated students’ experience with HART when the curriculum was required. All one hundred eleven members of the class of 2019 University of New Mexico School of Medicine students were required to enroll in HART. We surveyed the students before and after the course to assess its self-reported impact on key elements of professional (...) identity formation such as empathy towards patients and peers, commitment to service, and burnout. A majority of students reported positive effects of the course on their empathy towards other students. This finding was significantly associated with self-reported willingness to have elected the course had it not been required. One-half of respondents reported positive effects on their empathy towards future patients. At least one-quarter to one-third of respondents reported positive influences on commitment to service, conceptions about being a physician, and self-perceived burnout. Students report benefits on their professional identity formation after participating in a required course on humanism. Empathy-building among peers is one valuable outcome of such curricula. (shrink)

Companies are increasingly using cause-related marketing campaigns to engage consumers during the purchase process and highlight their own corporate social responsibility initiatives. One growing trend among retailers is the use of charity campaigns, where cashiers or technologies solicit consumers to donate money at checkout. Though these checkout charity campaigns are ubiquitous, little is known about their impact on consumers or the psychological processes involved. This paper addresses this gap by examining the process by which checkout charity appeals may license consumers (...) to engage in “guilty pleasures” counter to injunctive norms. In a series of four studies, we affirm this hypothesis, presenting a novel methodological approach for providing evidence of a credits-based process. This method utilizes a Johnson-Neyman procedure to demonstrate how a charitable donation creates a “warm-glow” feeling that subsequent counter-injunctive consumption erodes. In other words, we directly observe individuals “cashing in” credits to pay for bad behavior. We discuss the ethical implications of such campaigns in light of the subsequent behavior they may license. (shrink)

Wilkinson (1991) suggests that the problems of polarity decisions and homoplasy in a cladistic analysis may be solved if cladists simply accept plesiomorphy as a reliable indicator of monophyly. Here we argue that: (1) Wilkinson's argument is based on misapprehension of synapomorphy and the problem of homoplasy; (2) His proposed methodology fails to consider the full ramifications of rooting, polarity, and parsimony; and (3) His method does not solve the problems he raises. We demonstrate the limitations of this methodology by (...) using Wilkinson's practical example. We find no justification for the assertion that plesiomorphy may reliably delimit monophyly and recommend against Wilkinson's suggested methodological revisions. (shrink)

Previous research has shown that na_ve participants display a high level of agreement when asked to choose or drawschematic representations, or image schemas, of concrete and abstract verbs [Proceedings of the 23rd Annual Meeting of the Cognitive Science Society, 2001, Erlbaum, Mawhah, NJ, p. 873]. For example, participants tended to ascribe a horizontal image schema to push, and a vertical image schema to respect. This consistency in offline data is preliminary evidence that language invokes spatial forms of representation. It also (...) provided norms that were used in the present research to investigate the activation of spatial image schemas during online language comprehension. We predicted that if comprehending a verb activates a spatial representation that is extended along a particular horizontal or vertical axis, it will affect other forms of spatial processing along that axis. Participants listened to short sentences while engaged in a visual discrimination task (Experiment 1) and a picture memory task (Experiment 2). In both cases, reaction times showed an interaction between the horizontal/vertical nature of the verb's image schema, and the horizontal/vertical position of the visual stimuli. We argue that such spatial effects of verb comprehension provide evidence for the perceptual–motor character of linguistic representations. (shrink)

Extensive media coverage of the nation’s response to its obligation to furnish health care for service members wounded in current overseas conflicts in Iraq and Afghanistan has elevated public consciousness of the importance of the U.S. military and veteran’s health care systems to a level not seen since the end of the Vietnam War. The number of casualties of U.S. military engagements has varied in each specific conflict and is a direct result of both the type of battle and the (...) military’s ability to handle battlefield injuries. (shrink)

Drawing on insights from evolutionary psychology and modern neuroscience, this paper highlights propositions about human nature that have far reaching consequences, when applied to leadership. We specifically examine the main factors of human survival and extend them to a model for leadership in the twenty-first century. The discussion concludes with an outlook on the organizational and structural conditions that would allow for better and more balanced leadership.

The thought that human embryos could command moral respect yet also be acceptably used in medical research has struck some as incoherent. Given some assumptions about why they deserve respect, however, the thought is not objectionable, indeed not even unusual.

Health care reform is an important issue in the 2004 presidential elections and is receiving serious attention from the Democratic and Republican candidates. Changes in the economy that fuelled increased productivity and depressed job growth have also shifted more of the costs of medical care and insurance onto employees. The rising costs of insurance premiums and health care are far outpacing the general inflation rate and workers’ wages. Meanwhile, state governments reacted to widening budget deficits from 2001 to 2003 by (...) reducing Medicaid eligibility and benefits. These changes in employer-based health insurance and government policy have contributed to the largest rise in the share of Americans without health insurance in a decade. In 2002, the uninsured numbered 43.6 million and, according to the Congressional Budget Office, 57 to 59 million non-elderly people are uninsured at some point over the course of a year. (shrink)

Although the volume of the surviving papers of Robert Boyle is substantial (over 20,000 leaves), a considerable amount of the written material left by Boyle at his death in 1691 has not survived in the Boyle archive. This paper gauges the scale and identity of these losses using the surviving inventories made by the Rev. Henry Miles in the 1740s when he was collecting and sorting Boyle's literary remains in conjunction with Thomas Birch's preparation of his 1744 Life and Works (...) of Boyle. These detailed lists (edited as appendices to this paper), together with other sources, indicate losses due to a variety of reasons, some deliberate, others accidental. The losses involved the disposal of both items judged (in the eighteenth century) to be peripheral to Boyle's archive and, ironically, those in the most finished state from Boyle's hand, which were perhaps abortively destined for the Birch edition. These losses have significantly altered the character of the Boyle Papers, and thus the view of Boyle that is derived from them. (shrink)

As one of the most important ethicists to emerge since the Second World War, Alan Gewirth continues to influence philosophical debates concerning morality. In this ground-breaking book, Gewirth's neo-Kantianism, and the communitarian problems discussed, form a dialogue on the foundation of moral theory. Themes of agent-centered constraints, the formal structure of theories, and the relationship between freedom and duty are examined along with such new perspectives as feminism, the Stoics, and Sartre. Gewirth offers a picture of the philosopher's theory and (...) its applications, providing a richer, more complete critical assessement than any which has occurred to date. (shrink)

The Rediscovery of the mind By John Searle MIT Press, 1992. Pp. xv + 270. ISBN 0–262–19321–3 £19.95 hbk.The Ethics of Authenticity By Charles Taylor Harvard University Press, 1991. Pp. 152. ISBN 0–674–26863–6. $17.95Multiculturalism and ‘The Politics of Recognition’ By Charles Taylor Princeton University Press, 1992. p. 112. ISBN 0–691–0878–65. $14.95New books on feminismAbjection, Melancholia and Love: The Work of Julia Kristeva By John Fletcher and Andrew Benjamin Routledge, 1990. Pp. 224. ISBN 0–415–04155–4. £35 hbk.Feminist Literary Studies: An Introduction By (...) K. K. Ruthven Canto, 1991 (first published 1984). Pp. 152 ISBN 0–521–398525. £4.95 pbk.Socialism, Feminism and Philosophy: A Radical Philosophy Reader Edited by Sean Sayers and Peter Sayers Routledge, 1990. Pp. 256. ISBN 0–415–05627–6. £35 hbk.Luce Irigaray: Philosophy in the Feminine By Margaret Whitford Routledge, 1991. Pp. 304. ISBN 0–415–05968–2. £35 hbk.New books on wittgensteinWittgenstein's Philosophical Investigations. Text and Context Edited by Robert C. Arrington and Hans‐Johann Glock Routledge, 1992. Pp. 256. ISBN 0415–07035‐X. £35.00 hbk.Wittgenstein on Words as Instruments. Lessons in Philosophical Psychology By J. M. F. Hunter Savage, Barnes and Noble Books, 1990. Pp. 192. ISBN 0–389–20920–1. $42.00Wittgenstein on Ethics and Religious Belief By Cyrill Barrett Blackwell, 1991. Pp. 304. ISBN 0–631–16815‐X. £45.00. (shrink)

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers can freely discuss current and emerging deep brain stimulation technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in (...) its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury. (shrink)

Previous research has demonstrated that reversing the contrast of the eye region, which includes the eyebrows, affects the N170 ERP. To selectively assess the impact of just the eyes, the present study evaluated the N170 in response to reversing contrast polarity of just the iris and sclera in upright and inverted face stimuli. Contrast reversal of the eyes increased the amplitude of the N170 for upright faces, but not for inverted faces, suggesting that the contrast of eyes is an important (...) contributor to the N170 ERP. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

This second volume of Michael Black's commentary on Lawrence's prose works concentrates on the extraordinary sequence of nonfiction texts written between 1913 and 1917: The "Foreword" to Sons and Lovers, Study of Thomas Hardy, Twilight in Italy, "The Crown," "The Reality of Peace." In all of them Lawrence was compulsively rewriting what he called "my philosophy." They are difficult works: highly metaphorical, in places prophetically expressionist, even surreal. This extended commentary makes sense of them, treating them as (...) a succession of experimental writings that support each other, develop non-discursive modes of writing, and are linked by shared metaphors that reveal shared preoccupations. Black's highly useful analysis is like the close reading of poetry. (shrink)

This book is comprised of essays previously published in Philosophy & Public Affairs and also an extended excerpt from Michael Walzer's Just and Unjust Wars.