An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting (...) in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

An understanding of underlying mechanisms involved in the activation of HIF‐1 in response to both hypoxic stress and oncogenic signals has important implications for how these processes may become deregulated in human cancer. Changes in microenvironmental stimuli such as hypoxia and growth factors in combination with genetic lesions, such as loss or inactivation of p53, PTEN or pVHL or oncogenic activation, can all lead to increased HIF‐1 activity. This provides cancer cells with a distinct advantage for survival and proliferation, resulting (...) in their ability to form vascular tumours, which are aggressive and metastatic. Accordingly, upregulation of HIF‐1α, a key component of HIF‐1, correlates with a poor treatment outcome using conventional therapies. A variety of mechanisms exist that regulate expression of HIF‐1α. In recent years, it has become clear that an extensive network of signalling cascades converge on HIF‐1α to regulate the transcriptional response. A better understanding of this regulation may provide a basis for the development of new cancer therapies. BioEssays 26:262–269, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This new essay collection by distinguished philosopher Margaret Gilbert provides a richly textured argument for the importance of joint commitment in our personal and public lives. Topics covered by this diverse range of essays range from marital love to patriotism, from promissory obligation to the unity of the European Union.

Margaret Gilbert presents the first full-length treatment of a central class of rights: demand-rights. To have such a right is to have the standing or authority to demand a particular action of another person. Gilbert argues that joint commitment is a ground of demand-rights, and gives joint commitment accounts of both agreements and promises.

One of the most distinguished living social philosophers, Margaret Gilbert develops and extends her application of plural subject theory of human sociality, first introduced in her earlier works On Social Facts and Living Together. Sociality and Responsibility presents an extended discussion of her proposal that joint commitments inherently involve obligations and rights, proposing, in effect, a new theory of obligations and rights. In addition, it demonstrates the extensive range and fruitfulness of plural subject theory by presenting accounts of social (...) rules, scientific change, political obligation, collective remorse, collective guilt, shared intention and an important class of rights and obligations. (shrink)

This book is available either individually, or as part of the specially-priced Arguments of the Philosphers Collection.

The moral expertise of clinical ethicists is not a question of mastering codelike theories and lawlike principles. Rather, ethicists are architects of moral space within the health care setting, as well as mediators in the conversations taking place within that space.

To be truly reflective, moral thinking and moral philosophy must become aware of the contexts that bind our thinking about how to live. These essays show how to do this, and why it makes a difference.

Brain–computer interfaces are a form of technology that read a user’s neural signals to perform a task, often with the aim of inferring user intention. They demonstrate potential in a wide range of clinical, commercial, and personal applications. But BCIs are not always simple to operate, and even with training some BCI users do not operate their systems as intended. Many researchers have described this phenomenon as “BCI illiteracy,” and a body of research has emerged aiming to characterize, predict, and (...) solve this perceived problem. However, BCI illiteracy is an inadequate concept for explaining difficulty that users face in operating BCI systems. BCI illiteracy is a methodologically weak concept; furthermore, it relies on the flawed assumption that BCI users possess physiological or functional traits that prevent proficient performance during BCI use. Alternative concepts to BCI illiteracy may offer better outcomes for prospective users and may avoid the conceptual pitfalls that BCI illiteracy brings to the BCI research process. (shrink)

Work on representing women's voices in ethics has produced a vision of moral understanding profoundly subversive of the traditional philosophical conception of moral knowledge. I explicate this alternative moral "epistemology," identify how it challenges the prevailing view, and indicate some of its resources for a liberatory feminist critique of philosophical ethics.

This article will compare and contrast two very different accounts of convention: the game-theoretical account of Lewis in Convention, and the account initially proposed by Margaret Gilbert (the present author) in chapter six of On Social Facts, and further elaborated here. Gilbert’s account is not a variant of Lewis’s. It was arrived at in part as the result of a detailed critique of Lewis’s account in relation to a central everyday concept of a social convention. An account of convention (...) need not be judged by that standard. Perhaps it reveals the nature of an important phenomenon. Looked at in that light, these very different accounts are not incompatible. Indeed, neither should be ignored if one is seeking to understand the way in which human beings arrive at some degree of social order. (shrink)

It is widely accepted that only the victim of a wrong can forgive that wrong. Several philosophers have recently defended “third-party forgiveness,” the scenario in which A, who is not the victim of a wrong in any sense, forgives B for a wrong B did to C. Focusing on Glen Pettigrove's argument for third-party forgiveness, I will defend the victim's unique standing to forgive, by appealing to the fact that in forgiving, victims must absorb severe and inescapable costs of distinctive (...) kinds, a plight that third parties do not share. There are, nonetheless, significant, even essential, roles played by third parties in making forgiveness possible, reasonable, or valuable for victims of serious wrongs. I take a closer look at the links between victims, wrongdoers, resentment, and forgiveness in showing why the victim alone can forgive. (shrink)

: International instruments now defend a "right to the truth " for victims of political repression and violence and include truth telling about human rights violations as a kind of reparation as well as a form of redress. While truth telling about violations is obviously a condition of redress or repair for violations, it may not be clear how truth telling itself is a kind of reparations. By showing that concerted truth telling can satisfy four features of suitable reparations vehicles, (...) I defend the idea that politically implemented modes of truth telling to, for, and by those who are victims of gross violation and injustice may with good reason be counted as a kind of reparations. Understanding the doubly symbolic character of reparations, however, makes clearer why truth telling is unlikely to be sufficient reparation for serious wrongs and is likely to be sensitive to the larger context of reparative activity and its social, political, and historical background. (shrink)

A philosophy of management that incorporates the big picture of human experience, all levels, and degrees of awareness in relationship with the world, will better develop and sustain an environment conducive to creative contributions that meet organizational goals. Quantum physics reveals the nature of reality to be connection and creativity engaged in a process of actualizing possibilities. Human beings participate in this process of actualization, as both observer-creator and experiencer of the universe through multiple domains of knowing – a collaborator (...) in Alfred North Whitehead’s panexperientialism. Whitehead’s God of process, the primordial field of creative possibilities, and the consequent nature which holds all the experiences of every actualization, supports human consciousness, as it self-actualizes by engaging and integrating the experience of external and internal events and their effects on awareness. Through understanding the participatory nature of consciousness with God and the world as experienced, deep meaning emerges for human life. Tapping into this deeper meaning through a philosophy of management that acknowledges the full human experience, including the embedded spiritual connection to the creative energy that is God, strengthens an organization’s vision, mission and contributions to a community. This brief overview traces a path toward a preliminary framework for a philosophy of management based on God and the ideas of connection, creativity and process. (shrink)

Feminist discussions of ethics in the Western philosophical tradition range from critiques of the substance of dominant moral theories to critiques of the very practice of "doing ethics" itself. I argue that these critiques really target a certain historically specific model of ethics and moral theory-a "theoretical-juridical" one. I outline an "expressive-collaborative" conception of morality and ethics that could be a politically self-conscious and reflexively critical alternative.

The third and fourth books of Cicero's _Tusculan Disputations_ deal with the nature and management of human emotion: first grief, then the emotions in general. In lively and accessible style, Cicero presents the insights of Greek philosophers on the subject, reporting the views of Epicureans and Peripatetics and giving a detailed account of the Stoic position, which he himself favors for its close reasoning and moral earnestness. Both the specialist and the general reader will be fascinated by the Stoics' analysis (...) of the causes of grief, their classification of emotions by genus and species, their lists of oddly named character flaws, and by the philosophical debate that develops over the utility of anger in politics and war. Margaret Graver's elegant and idiomatic translation makes Cicero's work accessible not just to classicists but to anyone interested in ancient philosophy and psychotherapy or in the philosophy of emotion. The accompanying commentary explains the philosophical concepts discussed in the text and supplies many helpful parallels from Greek sources. (shrink)

This chapter examines one of the most serious problems with the principle of self‐determination, viz., that this concept does not tell us who the peoples are that are entitled to self‐determination or the jurisdictional unit that they are entitled. It examines indigenous, historical, superior culture, and occupancy arguments for rights to a particular territory and suggests normative principles for thinking about jurisdictional units.

In this exploratory paper, we investigate the extension of Haidt’s :814–834, 2001, The righteous mind: Why good people are divided by politics and religion, 2012) Moral foundations theory, operationalized as the MFQ30 questionnaire, from a sample of the general public across many countries to a sample of business students. MFT posits that people rely on five major concerns, or foundations, when making moral judgments. The five concerns are care/harm, fairness/cheating, loyalty/betrayal, respect/authority, and purity/degradation. In addition, Haidt suggests that intuition, rather (...) than reasoning, leads to moral judgment. We replicate Haidt’s measurement model and find that the measurement model based on our sample is consistent. This indicates support for MFT. Further, we find structural differences in the measurement model between the genders and between areas of study. Our findings suggest that all students in the sample focus substantially on the fairness foundation. Ethics education and research may seek to expand the number of moral foundations individuals consider when discerning whether something is right or wrong. (shrink)

This chapter offers a conceptual analysis of territory, distinguishes it from property accounts, and discusses different versions of property accounts, all derived from Locke’s ‘Second Treatise of Government’. It offers a conceptual analysis of territory and the various rights associated with territory. According to Locke, territorial right is established through the subjection, by free consent, of persons and their land to state authority. This theory is found to rest on a number of flawed assumptions, among them claims to natural rights (...) of property and an obvious link between private property and territorial jurisdiction. Cara Nine draws on Lockean principles to claim that a state is a collective that, like individuals, owns property, namely the territory of the state. After examining the historical antecedents of such ideas, the chapter points away from them and towards accounts of territory based on individual and collective claims of rights. (shrink)

This article argues that Hume's brief essay, "Of the Delicacy of Taste and Passion," offers resources for three claims: (1) Delicate taste correlates with self-sufficiency and thus with a particularly Humean form of Magnanimity -- greatness of mind; (2) Delicate taste improves the capacity for profound friendships, characterized by mutual admiration and true compassion; and (3) magnanimity and compassion are thus not necessarily in tension with one another and may even proceed from and support harmony of character. These claims, in (...) turn, provide reasons to take seriously Hume's view that moral character depends, in part, on aesthetic character. (shrink)

This article recontextualizes Irigaray with reference to post-Freudian psychoanalytic theories of narcissism, and argues that a persistent theme in her work has been the diagnosis of the narcissism of Western culture. It indicates that one of the possible sources for her diagnosis of Western culture is the work of Béla Grunberger. It also argues that it is possible to make connections between Irigaray's critique of Western civilization and other related critiques. The second part of the article sketches a brief account (...) of the Kleinian and post-Kleinian concept of projective identification, and argues that reinterpreting Irigaray in the light of this concept can help to shed more light on her account of the significance of the maternal container. (shrink)

The systemic difficulties of health care in the USA have brought to light another issue in nurse—patient advocacy — those who require care yet have inadequate or non-existent access. Patient advocacy has focused on individual nurses who in turn advocate for individual patients, yet, while supporting individual patients is a worthy goal of patient advocacy, systemic problems cannot be adequately addressed in this way. The difficulties nurses face when advocating for patients is well documented in the nursing literature and I (...) argue that, through collective advocacy, professional nursing associations ought to extend the reach of individual nurses in order to address systemic problems in health care institutions and bureaucracies. (shrink)