Interleukin 1β‐converting enzyme (ICE)‐like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA‐dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can (...) cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis. (shrink)

We are developing the Neurological Disease Ontology (ND) to provide a framework to enable representation of aspects of neurological diseases that are relevant to their treatment and study. ND is a representational tool that addresses the need for unambiguous annotation, storage, and retrieval of data associated with the treatment and study of neurological diseases. ND is being developed in compliance with the Open Biomedical Ontology Foundry principles and builds upon the paradigm established by the Ontology for General Medical Science (OGMS) (...) for the representation of entities in the domain of disease and medical practice. Initial applications of ND will include the annotation and analysis of large data sets and patient records for Alzheimer’s disease, multiple sclerosis, and stroke. (shrink)

The paper investigates the status of gravitational energy in Newtonian Gravity, developing upon recent work by Dewar and Weatherall. The latter suggest that gravitational energy is a gauge quantity. This is potentially misleading: its gauge status crucially depends on the spacetime setting one adopts. In line with Møller-Nielsen’s plea for a motivational approach to symmetries, we supplement Dewar and Weatherall’s work by discussing gravitational energy–stress in Newtonian spacetime, Galilean spacetime, Maxwell-Huygens spacetime, and Newton–Cartan Theory. Although we ultimately concur with Dewar (...) and Weatherall that the notion of gravitational energy is problematic in NCT, our analysis goes beyond their work. The absence of an explicit definition of gravitational energy–stress in NCT somewhat detracts from the force of Dewar and Weatherall’s argument. We fill this gap by examining the supposed gauge status of prima facie plausible candidates—NCT analogues of gravitational energy–stress pseudotensors, the Komar mass, and the Bel-Robinson tensor. Our paper further strengthens Dewar and Weatherall’s results. In addition, it sheds more light upon the subtle link between sufficiently rich inertial structure and the definability of gravitational energy in NG. (shrink)

This article considers the idea of medicine’s internal morality as it is understood by its various proponents. Although the use of the phrase ‘internal morality’ in relation to medicine predates Ed...

Various philosophers have wanted to move from a (P.F.) “Strawsonian” understanding of the “practices of moral responsibility” to a non-skeptical result. I focus on a strategy moving from a “response-dependent” theory of responsibility. I aim to show that a key analogy associated with this strategy fails to support a compatibilist result. It seems clear that nothing could show that nothing we have been laughing at has really been funny. If “the funny” is similar to “the blameworthy”, then perhaps it would (...) follow that nothing could show that no one we have ever blamed has really been blameworthy. The comparison is interesting, but inconclusive: even if we grant that these properties are normatively similar, the latter has substantive empirical presuppositions, whereas the former does not. One important upshot: even if the standards operative in our practices cannot be mistaken, it could nevertheless be that no one has ever met these standards Ruling out this possibility seemingly requires re-engaging in all of the so-called "metaphysical" debates Strawsonians are keen to avoid. (shrink)

Moral latitude is only ever a matter of coincidence on the most popular decision procedure in the literature on moral uncertainty. In all possible choice situations other than those in which two or more options happen to be tied for maximal expected choiceworthiness, Maximize Expected Choiceworthiness implies that only one possible option is uniquely appropriate. A better theory of appropriateness would be more sensitive to the decision maker’s credence in theories that endorse agent-centred prerogatives. In this paper, we will develop (...) and defend a modified version of this view that allows for agent-centred prerogatives and supererogation as part of its verdicts about appropriateness. (shrink)

This modern, advanced textbook reviews modal logic, a field which caught the attention of computer scientists in the late 1970's.

"'There is only one thing that is certain, namely that we can have nothing certain; and therefore it is not certain that we can have nothing certain,' Samuel Butler once said, expressing in that mindbloggler all the elements required to form a classical paradox. Throughout the ages wise men and jesters alike have been intrigued by such mental twists and riddles which defy common sense and yet appear to be true." -- Dust jacket.

The future health of children depends on clinical research which is an important part of medical progress. The principles of the child’s best interests standards and how it is applied in the context of research are explored. This review will show that there is a need for research involving children but there are gaps in the current legal and ethical framework which are not readily applicable to non-therapeutic research involving children. There are significant challenges in trying to achieve a balance (...) between what is socially good and the obligation to protect children who participate in research. (shrink)

In this highly acclaimed book, one of the most prominent theologians in the world offers a theological and psychoanalytic assessment of Freud's atheism and of its implications for current psychoanalytic practice.

Inductively defined structures are ubiquitous in mathematics; their specification is unambiguous and their properties are powerful. All fields of mathematical logic feature these structures prominently: the formula of a language, the set of theorems, the natural numbers, the primitive recursive functions, the constructive number classes and segments of the cumulative hierarchy of sets. -/- This dissertation gives a mathematical characterization of a species of inductively defined structures, called accessible domains, which include all of the above examples except the set of (...) theorems. The concept of an accessible domain comes from Wilfried Sieg's analysis of proof-theoretic practices, starting with his dissertation. In particular, he noticed the special epistemological character of elements of an accessible domain: they can always be uniquely identified with their build-up. Generally, the unique build-up of elements justifies the principles of induction and recursion. -/- I use category theory to give an abstract characterization of accessible domains. I claim that accessible domains are all instances of initial algebras for endofunctors. Grounded in the historical roots of Sieg's discussions, this dissertation shows how the properties of initial algebras for endofunctors and accessible domains coincide in a satisfying and natural way. -/- Filling out this characterization, I show how important examples of accessible domains fit into this broad characterization. I first characterize some accessible domains by relatively simple functors (e.g. finite, polynomial, those that preserve certain colimits) where we can see how iterating the functor can produce the accessible domain. Then I describe accessible domains that result from more involved specifications (e.g. ordinals and segments of the cumulative hierarchies associated with CZF, IZF, and ZF) by relying heavily on algebraic set theory. I end with a discussion of some of the methodological features of category theory in particular that helped characterize accessible domains. (shrink)

As the twentieth century draws to a close and the rush to globalization gathers momentum, political and economic considerations are crowding out vital ethical questions about the shape of our future. Now, Hans Kung, one of the world's preeminent Christian theologians, explores these issues in a visionary and cautionary look at the coming global society. How can the new world order of the twenty first century avoid the horrors of the twentieth? Will nations form a real community or continue to (...) aggressively pursue their own interests? Will the Machiavellian approaches of the past prevail over idealism and a more humanitarian politics? What role can religion play in a world increasingly dominated by transnational corporations? Kung tackles these and many other questions with the insight and moral authority that comes from a lifetime's devotion to the search for justice and human dignity. Arguing against both an amoral realpolitik and an immoral resurgence of laissez faire economics, Kung defines a comprehensive ethicfounded on the bedrock of mutual respect and humane treatment of all beingsthat would encompass the ecological, legal, technological, and social patterns that are reshaping civilization. If we are going to have a global economy, a global technology, a global media, Kung argues, we must also have a global ethic to which all nations, and peoples of the most varied backgrounds and beliefs, can commit themselves. "The world," he says, "is not going to be held together by the Internet." For anyone concerned about the world we are creating, A Global Ethic for Global Politics and Economics offers equal measures of informed analysis, compassionate foresight, and wise counsel. (shrink)

(2006). The Normative Justification of Traditional Chinese Authoritarianism. Critical Review of International Social and Political Philosophy: Vol. 9, No. 3, pp. 379-397.

We present an argument in support of the legal prohibition of infant male circumcision (IMC) in developed Western countries. We submit that all IMC, irrespective of whether the motivation behind it be secular or religious, violates children’s rights to self-determination (autonomy) and bodily integrity and is therefore morally illegitimate. And while IMC’s being morally wrong does not entail that it ought to be criminalised, we contend that it should be legally proscribed so as to protect children against harm and to (...) uphold their rights. We consider and reject an argument that an exemption from the legal ban should be granted to religious parents who perceive themselves to be under a moral obligation to subject their male infants to IMC. We argue that since IMC sets back children’s basic interests and violates their rights, there is no room, and no case, for the conferring of a religious exemption. (shrink)

Thomas Aquinas has argued that the passion of hope is the movement of the sensitive appetite and the first of the irascible passion. The first part of the article aims to explore the cause and the mechanism of the passion of hope, and tries to clarify the relationship between the passion of hope and the perception. In human beings, it is possible that the passion of hope is caused by false judgement of the perception, which will lead to the result (...) of false hope. In Aquinas’s argument, the problem of false hope could be solved through the moral virtue and the prudence. In the second part of this article, the aim is to analyse how the virtue of magnanimity, humility and the prudence work impact on the passion of hope and perfect it.Contribution: This research concentrates on the topic of the passion of hope of Thomas Aquinas, and provides a new perspective on the understanding of the relationship between the passion and the virtue. (shrink)

At least since Aristotle's famous discussion of the sea-battle tomorrow in On Interpretation 9, philosophers have been fascinated by a rich set of interconnecte.

The goal of this study was to construct a valid new instrument to measure the effect of moral intensity on managers' propensity to manage earnings. More specifically, this study is a pilot study of the impact of moral intensity on financial accountants' propensity to manage earnings. The instrument, once validated, will be used in a full-study of managers in the hotel industry. Different ethical scenarios were presented to respondents in the survey; each ethical scenario was designed in both high or (...) low moral intensity form, to reflect the importance of the moral dilemma at hand. The results were analysed by factor analysis. The findings of this study have positively validated the instrument, with three of the five moral intensity components identified as having appropriate eigenvalues. This indicates that they have a significant influence in the study. The first factor captures the social consensus dimension and one scenario of the proximity dimension. The second factor indicates an interaction between the temporal immediacy and the magnitude of consequences dimension. The third dimension is probability of effect and one scenario of the proximity dimension. In addition, t-tests indicated that the manipulation of high and low conditions within each scenario were also successful. One limitation of the study might be the use of undergraduate accounting students as manager proxies, although prior evidence suggests use of accounting students as proxies is a valid approach in this type of study. This is a highly novel project as most prior studies have focussed on moral intensity and the general ethical decision-making process. (shrink)

_"One of the most important political books of 2018."—Rod Dreher, ___American Conservative__ Of the three dominant ideologies of the twentieth century—fascism, communism, and liberalism—only the last remains. This has created a peculiar situation in which liberalism’s proponents tend to forget that it _is _an ideology and not the natural end-state of human political evolution. As Patrick Deneen argues in this provocative book, liberalism is built on a foundation of contradictions: it trumpets equal rights while fostering incomparable material inequality; its (...) legitimacy rests on consent, yet it discourages civic commitments in favor of privatism; and in its pursuit of individual autonomy, it has given rise to the most far-reaching, comprehensive state system in human history. Here, Deneen offers an astringent warning that the centripetal forces now at work on our political culture are not superficial flaws but inherent features of a system whose success is generating its own failure. (shrink)

Adolescents who believe that their parents treat them differently from their siblings have poorer psychosocial well-being than otherwise. This phenomenon, which is known as parental differential treatment or PDT occurs in up to 65% of families. Past studies have examined socio-demographic variables (e.g., child gender, age, and birth order) as predictors of PDT, but these immutable characteristics do little to inform interventions and help these adolescents. Hence, this study extends past research by investigating links among parent empathy, parent perception of (...) PDT, child perception of PDT, child perception of fairness and child well-being (self-esteem, depression, anxiety, and trust in the relationship with parents). Furthermore, this study tests whether adolescent personality (openness, conscientiousness, extraversion, agreeableness and neuroticism), child empathy, and child perception of fairness moderate these links. This study will utilize a two-wave longitudinal design with a one-year lapse. Data will be collected from 760 Chinese adolescents studying from Secondary One to Secondary Three in 18 schools in Hong Kong and from their parents. We test our theoretical model via a multilevel structural equation model. This study both addresses (a) theoretical debates about relations among empathy, PDT, fairness, and psychosocial well-being and (b) focuses on modifiable factors and behaviors, to inform future interventions, such as parent education. (shrink)

"A thematic exposition focused on the "whole man," especially in his practical, aesthetic, ethical, and religious dimensions, moving from consideration of the stream of consciousness and consciousness as selective according to interests, through the ethical and religious aspects of man's aspiration and experience, to the humanistic bases of James' pragmatism and radical empiricism ... Dooley's account is remarkably clear and streamlined, stressing the consistency rather than the tensions in James' thought. Thus, while James' own texts provide at once the most (...) authoritative and the most attractive approach to his thought for readers at all levels, Dooley's book seems most likely to be helpful as supplementary reading for teachers and students in introductory courses.". (shrink)

This is an exploration of a cluster of related logical results. Taken together these seem to have something philosophically important to teach us: something about knowledge and truth and something about the logical impossibility of totalities of knowledge and truth. The book includes explorations of new forms of the ancient and venerable paradox of the :Liar, applications and extensions of Kaplan and Montague's paradox of the Knower, generalizations of Godel's work on incompleteness, and new uses of Cantorian diagonalization. Throughout, the (...) concern is with metaphysical and epistemological implications of these results: what such results may have to teach us about knowledge, truth, and possibility. (shrink)