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)

The author develops and elaborates on her account of collective belief, something standardly referred to, in her view, when we speak of what we believe. This paper focuses on a special response hearers may experience in the context of expressions of belief, a response that may issue in offended rebukes to the speaker. It is argued that this response would be appropriate if both speakers and hearers were parties to what the authors calls a joint commitment to believe a certain (...) proposition as a body. This joint commitment puts speakers under an obligation to refrain from speaking in certain ways, and gives hearers a correlative right to such refraining, and hence a basis for offended rebukes. (shrink)

Collective action is interpreted as a matter of people doing something together, and it is assumed that this involves their having a collective intention to do that thing together. The account of collective intention for which the author has argued elsewhere is presented. In terms that are explained, the parties are jointly committed to intend as a body that such-and-such. Collective action problems in the sense of rational choice theory—problems such as the various forms of coordination problem and the prisoner’s (...) dilemma—are then considered. An explanation is given of how, when such a problem is interpreted in terms of the parties’ inclinations, a suitable collective intention resolves the problem for agents who are rational in a broad sense other than the technical sense of game theory. Key Words: rationality • collective action • collective intention • joint commitment. (shrink)

Cognitive science is the project of understanding the mind by modelling its workings. Its development is one of the most remarkable and fascinating intellectual achievements of the modern era. Mind as Machine is a masterful history of cognitive science, told by one of its most eminent practitioners.

May social unity - the unity of a society or social group - be a matter of sharing values? Political philosophers disagree on this topic. Kymlicka answers: No. Devlin and Rawls answer: Yes. It is argued that given one common 'summative' account of sharing values a negative answer is correct. A positive answer is correct, however, given the plural subject account of sharing values. Given this account, those who share values are unified in a substantial way by their participation in (...) a joint commitment. Some consequences of such sharing of values for the liberty of the people involved are noted. (shrink)

Clough's theological account of animals critiques the familiar negative identification of animals as not-human. Instead, Clough highlights both the distinctive particularity of each animal as created by God and the shared fleshly creatureliness of human and nonhuman animals. He encourages Christians to recognize Jesus Christ as God enfleshed more than divinely human, and consequently to care for nonhuman animals as those who share with human animals in the redemption of all flesh. This move risks downplaying the possibilities for creaturely specific (...) forms of redemption; limiting the cosmic efficacy of salvation in Christ; and losing the particularity of Christ's divine and human natures. Another, possibly less risky, direction to take Clough's insights about creatureliness and well-formed theological ethics might attend to the perverse ways that humans assess the worthiness of human and nonhuman animals by substituting particularities of use and abuse for the particularities of creation and salvation. (shrink)

I argued that the frameworks and mechanisms that produce unification do not enable us to explain why the unified phenomena behave as they do. That is, we need to look beyond the unifying process for an explanation of these phenomena. Anya Plutynski ([2005]) has called into question my claim about the relationship between unification and explanation as well as my characterization of it in the context of the early synthesis of Mendelism with Darwinian natural selection. In this paper I argue (...) that her methodological criticisms rest on a misinterpretation of my views on explanation and defend my historical interpretation of the work of Fisher and Wright. A statement of the problem Methodological differences: how to characterize explanation Historical matters: disagreements about details Explanation revisited: the possible versus the ‘merely actual’. (shrink)

This collection reconsiders canonical figures and the formation of disciplinary boundaries during the Scientific Revolution.

European Journal of Political Theory, Volume 21, Issue 1, Page 25-46, January 2022. This article explains how 19th-century radical republicans answered the following question: how is it possible to be free in a social order that fosters economic dependence on others? I focus on the writings of a group of French thinkers called the solidarists who advocated “liberty organized for everyone.” Mutualism and social right were two components of the solidarist strategy for limiting domination in commercial/industrial society. While the doctrine (...) of mutualism was rooted in pre-industrial artisan culture, social right was a novel idea that built on Durkheim’s analysis of the division of labour. In this article, I describe the main features of the solidarist account: solidarity, social property, quasi-contractual debt, and restorative justice. Classical republicanism was deeply concerned with citizen participation and the balance between popular and elite power, but 19th-century radical republicans thought that these goals must be approached differently in market societies in which enormous power is exercised outside the state. The solidarists cautiously embraced the state as a mechanism for regulating the market in order to ensure equal liberty. Social right and mutualism were also conceived as ways of limiting the centralization of state power. (shrink)

While a national health care system may be greeted with enthusiasm on many grounds, it poses substantial moral problems – not the least of which would be the clash between the ‘standardization’ of care for the sake of efficiency and the needs of individual patients. Such problems are best seen in the treatment of dying patients. Keywords: best buy, cost-saving, dying, efficiency, practice guidelines, Rilke, standards of practice, two tier CiteULike Connotea Del.icio.us What's this?

This essay explores the nature of an important collective emotion, namely, collective remorse. Three accounts of collective remorse are presented and evaluated. The first involves an aggregate of group members remorseful over acts of their own associated with their group's act; the second an aggregate of persons remorseful over their group's act. The third account posits, in terms that are explained, a joint commitment of a group's members to constitute as far as is possible a single remorseful body. Construed according (...) to this account the remorse of a nation that has wronged another nation is liable to make a particularly important contribution to international peace. (shrink)

Volume 19, Issue 3, June 2020, Page 217-221.

In positioning his laudandus Hagesias as the co-founder of Syracuse, Pindar considers the larger ideological implications of including a seer in a colonial foundation. The poet begins Olympian 6 by praising Hagesias as an athletic victor, seer, and sunoikistêr and therefore as a figure of enormous ritual power. This portrayal, however, introduces an element of competition into Hagesias' relationship with his patron Hieron, the founder of Aitna. In response, the ode's subsequent mythic portions circumscribe Hagesias' status so as to mitigate (...) any challenge the seer might present to Hieron's own political authority. An intertextual reading of Olympian 6's myth with the myth of Pelops in Olympian 1 highlights Pindar's careful negotiation of Hagesias' position in this colonial context. Despite the resulting need to affirm Hagesias' subordination to Hieron, Pindar joins together the seemingly incompatible roles of seer and co-founder because, as an intertextual reading of Nemean 1 helps to illustrate, Hagesias embodies and symbolically enacts in the ode Hieron's synoikism of Aitna. (shrink)

Fog in August is a German film based on Robert Domes' historical novel of the same name. The film provides a fictionalized account of the institutionalization and eventual killing of children and adults labelled as a burden on the State and unworthy of life. On one level, this is a story of good versus evil, where innocent patients are manipulated by callous doctors and nurses. At a deeper level, however, it is possible to read the characters as more complex and (...) such a reading gives an insight into the paradox of how a genocidal policy was able to be systematically implemented by health care professionals who had previously taken an oath to provide care to all people. Carl Jung argued that powerful stories, told across generations, contain mythical archetypes that help drive the plot and convey beliefs about humanity. The aims of this paper are to explore Jungian ideas within Fog in August that help the historical story it is based on resonate with viewers today, and demonstrate how the application of these insights can help health care professionals more fully understand morally distressing events and, as a result, support and improve the safety of patients. (shrink)

The Adagia of Erasmus was first published in 1500. It went through numerous impressions and ten major revisions in the course of Erasmus's life. Its influence was incalculable. It disseminated humanist learning and humanist attitudes among the new reading public to such an extent that it can be claimed as one of the books that contributed most to form the European mind. The adages were proverbs or popular sayings taken from classical literature. Many are part of the common stock of (...) our speech today. A necessary evil, cupboard love, a rare bird, an iron in the fire, are all to be found in the Adagia. Erasmus refers each to its source; then follows with a commentary on the meaning and with whatever ideas and personal observations arose from it. The book's influence waned after his death. (shrink)

Courts in the United States are finding that recipients can be bound by fine-print terms if they had notice of them. Without directly confronting the overarching normative question whether notice can cause contractual obligation, this Article takes notice seriously by focusing on how psychological characteristics of “HUMANs” suggest rethinking of when effective notice is likely to occur.

In his paper on the “Methodology of Positive Economics”, Milton Friedman warned his readers that, “more than other scientists, social scientists need to be self-conscious about their methodology.” (1953, p. 34). But until quite recently, he seems either to have spoken to deaf ears or, more plausibly, to have been so successful in promoting his own views on methodology as to lead economists to be complacent about the many problems which plague their discipline. Many current textbooks, for example the one (...) by Eugene Silberberg, present economics as a science attaining the falsificationist standards once set down by Karl Popper, despite much evidence to the contrary. Indeed, as Douglas W. Hands (1985) has recently shown, even Sir Karl did not intend economics to be subjected to such severe standards. (shrink)

Critiques of the ‘global’ have, in recent years, concerned the alleged implication of cultural dominance and secondly—and more philosophically—discerned therein foundationalism/essentialism. These charges will be examined. I next turn to the bearing of organizational/faculty matters on our theme, drawing on teaching experience in more than one country. The relocation of philosophy cannot but raise questions about how the subject itself is conceived. In the final section I suggest that the original humanist import of philosophical studies needs recovery, with ‘globality’ examined (...) critically not only over space but across time. This would involve not only due appreciation of argument (for no discipline lacks this) but of language, standpoint and attitude. (shrink)

This brief comment was a contribution to a 1995 Symposium on Feminism and Philosophy in the 1990s held at the Pacific Division Meeting of the APA in conjunction with the Society for Philosophy and Public Affairs. I suggest the usefulness of paying attention to the differences among philosophers who are women; philosophers who are feminists; philosophers who do feminist philosophy; and philosophers who want to express their feminism in their roles as philosophers. Keeping these differences in mind might help us (...) to avoid mistaken and disrespectful assumptions about both philosophers and feminist philosophy. (shrink)

This book presents a critique of dominant governance theories grounded in an understanding of existence as a static, discrete, mechanistic process, while also identifying the failures of theories that assume dynamic alternatives of either a radically collectivist or individualist nature. Relationships between ontology and governance practices are established, drawing upon a wide range of social, political, and administrative theory. Employing the ideal-type method and dialectical analysis to establish meanings, the authors develop a typology of four dominant approaches to governance. The (...) authors then provide a systematic analysis of each governance approach, thoroughly unpacking and critiquing each one and exploring the relationships and movements among them that engender reform and revolution as well as retrenchment and obfuscation of power dynamics. After demonstrating that each governance approach has fatal flaws within a diverse global context, the authors propose an alternative they call Integrative Governance. As a synthesis of the ideal-types, Integrative Governance is neither individualist nor collectivist, while still maintaining the dynamic character required to accommodate responsiveness to cultural contexts. (shrink)