Serine proteinase cleavage of proteins is essential to a wide variety of biological processes and is primarily regulated by protein inhibitors. Many inhibitors are conformationally rigid simulations of optimal serine proteinase substrates, which makes them highly efficient competitive inhibitors of target proteinases. In contrast, members of the serpin family of serine proteinase inhibitors display extensive flexibility and polymorphism, particularly in their reactive site segments and in β‐sheet secondary structure, which can take up and expel strands. Reactive site and β‐sheet polymorphism (...) appear to be coupled in the serpins and may account for the extreme stability of serpinproteinase complexes through the insertion of the reactive site strand into a β‐sheet. These unusual properties may have opened an adaptive pathway of proteinase regulation that was unavailable to the conformationally rigid proteinase inhibitors. (shrink)

This reader has been assembled in response to increasing dissatisfaction among a growing number of international relations scholars with the currently dominant theory of realism as well as in recognition of the large number of newly independent states which are having to write new constitutions and develop foreign relations. The book includes excerpts and essays from political theory and international relations which provide a starting point for further study of these subjects. It draws together writings representing two distinct traditions and (...) demonstrates their interconnections. In political theory, excerpts are drawn from classical texts which have an important bearing on problems of international relations. In international relations, the collection includes essays which have had a seminal influence on the development of this discipline. (shrink)

Theories of consciousness have a long and controversial history. One well-known proposal — integrated information theory — has recently been labeled as ‘pseudoscience’, which has caused a heated open debate. Here we discuss the case and argue that the theory is indeed unscientific because its core claims are untestable even in principle.

COVID-19 has uncovered the vulnerabilities, inequalities and fragility present within our social community which has exposed and exacerbated the pre-existing racial and socioeconomic inequalities that disproportionately affect health outcomes for Black, Asian and Minority Ethnic (BAME) people. Such disparities are fuelled by complex socioeconomic health determinants and longstanding structural inequalities. This paper aims to explore the inequalities and vulnerabilities of BAME communities laid bare by the Public Health England (PHE) reports published in June 2020, concluding with suggested strategies to address (...) inequalities in a post COVID-19 recovery. (shrink)

What is the young Marx's attitude towards questions of psychology? More precisely, what is his attitude towards the human mind and its relationship to the body? To deal adequately with this issue requires a consideration of the relationship between Marx and Feuerbach. It also requires some discussion of the thought of Aristotle. For the views of Feuerbach and the young Marx are not at all original. Rather, they represent a continuation of a long tradition which derives ultimately from ancient Greek (...) philosophy, and especially from the philosophy of Aristotle. As is well known, Aristotle's thought with respect to questions of psychology are mostly presented, by way of a critique of the doctrines of the other philosophers of his day, in his De Anima. W.H. Walsh has made the perceptive observation that Aristotle's views might be seen as an attempt to develop a third approach which avoids the pitfalls usually associated with the idealism of Plato, on the one hand, and the materialism of Democritus on the other. It might be argued that there is an analogy between the situation in which Aristotle found himself in relation to the idealists and materialists of his own day and that which confronted Marx in the very early 1840s. For, like Aristotle, Marx also might be seen as attempting to develop such a third approach. The difference is simply that, in the case of Marx, the idealism in question is that of Hegel rather than that of Plato, and the materialism is the ‘mechanical materialism’ of the eighteenth century rather than that of Democritus. This obvious parallel might well explain why Marx took such a great interest in Aristotle's De Anima both during and shortly after doing the preparatory work for his doctoral dissertation – the subject matter of which, of course, is precisely the materialist philosophy of the ancient Greek atomists Democritus and Epicurus. (shrink)

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, Georgetown (...) University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

In this paper I defend a pluralistic approach in understanding function, both in biological and other contexts. Talks about function are ubiquitous and crucial in biology, and it might be the key to bridge the “manifest image” and the “scientific image” identified by Sellars (1962). However, analysis of function has proven to be extremely difficult. The major puzzle is to make sense of “time-reversed causality”: how can property P be the cause of its realizer R? For example, “pumping blood” is (...) a property of hearts, but a property of hearts cannot be the cause of the presence of hearts, since properties cannot predate their realizers and be causes of them. In section 2 I discuss Wright’s etiological analysis, Cummins’ causal-role analysis, and their critics. In section 3 I defend a version of the “consensus without unity” strategy proposed by Godfrey-Smith from Christopher Boorse’s recent critique (2002). In Section 4 I conclude by reflecting on the relation between functional discourses and physicalism. (shrink)

This note analyses a recent case of the English Court of Appeal in which the applicant, R.G., a gay, H.I.V. positive Colombian claimed asylum on grounds of persecution due to his sexuality. Both the Asylum and Immigration Tribunal and the Court of Appeal rejected R.G.’s claim for asylum. The Court of Appeal’s first and most significant reason was that the alleged persecution was not sufficiently serious or life threatening, since R.G. had not suffered actual physical violence throughout the 13 years (...) that he had lived as a closeted gay man in Colombia. Secondly, the court considered the real reason for R.G.’s seeking asylum was his desire to access free health care in order to manage his H.I.V. His allegations of persecution on the grounds of sexuality were viewed as a sham. This note is critical of the approach taken by the Court, which, it is argued, displays an insensitivity to the complexity of sexual identity and its performance and has the effect of perpetuating and legitimating discrimination against lesbians and gay men. (shrink)

This essay is an inquiry into John McDowell’s thinking on ‘subjectivity.’ The project consists in two parts. On the one hand, I will discuss how McDowell understands and responds to the various issues he is tackling; on the other, I will approach relevant issues concerning subjectivity by considering different aspects of it: a subject as a perceiver, knower, thinker, speaker, agent, person and (self-) conscious being in the world. The inquiry begins by identifying and resolving a tension generated by the (...) very idea of ‘rational animal’: human beings are at the same time natural and rational. Later the inquiry proceeds by considering how McDowell’s notion of ‘second nature’ enables us to be human subjects with many faces. By going through the diagnoses and responses of McDowell, two central problems in modern and contemporary philosophy – the narrow conception of nature and the Cartesian inner space model – are identified and repelled. In Episode N I first urge that we should leave room for a certain notion of ‘world.’ I further argue that mentality has many aspects, and to understand those aspects is to understand the many faces of human subject. In Episode Ⅰ the Aristotelian notion of ‘second nature’ is discussed in order to resolve the tension in the very idea of ‘rational animal.’ Later I reply to some worries about this maneuver, including the objection from Crispin Wright. Hans-Georg Gadamer’s distinction between world and environment is introduced and related to McDowell’s thinking. Episode Ⅱ discusses perception and knowledge; McDowell’s main target – the Cartesian inner space – is introduced and criticized. Barry Stroud’s and Simon Blackburn’s positions are evaluated. Later I connect the main theme of Mind and World to the present context; in particular, I discuss McDowell’s invocation of Donald Davidson and Immanuel Kant. And then I discuss a common accusation of idealism, and Robert Brandom’s accusation of ‘residual individualism.’ Episode Ⅲ concentrates on Saul Kripke’s Wittgenstein, arguing that the master thesis behind the rule-following paradox is a version of the inner space model, and that Kripke’s Wittgenstein is not Wittgenstein. Martin Kusch’s objections are answered; Michael Dummett’s demand of reductionism is rebutted. After this, I turn to Davidson’s ‘no language’ claim, and discuss to what extent McDowell agrees with him. In Episode Ⅳ I evaluate objections from Hubert Dreyfus concerning action and agency. I discuss how Dreyfus and Maurice Merleau-Ponty commit ‘the Myth of the Disembodied Intellect’ identified by McDowell. I answer Michael Ayer’s charge of intellectualism in passing. Later I bring in McDowell’s objections to Derek Parfit on personhood and to Davidson on the mind-body relation. In Episode Ⅴ I focus on consciousness and self-consciousness. McDowell applies his argument against Parfit to Kant, but Maximilian de Gaynesford dissents. I reply to his objections on McDowell’s behalf. I further connect this to McDowell’s attacks on the dualism of scheme and content. This leads to my McDowellian rejection to the existence of qualia, and further brings me to the debate between intentionalism and disjunctivism in the context of the argument from illusion. I argue against Tim Crane’s ways of conceiving issues about intentionalism and the argument from illusion. Varieties of disjunctivism are also discussed. In my Epilogue, I express my worry about McDowell’s notion of ‘self-determining subjectivity.’ According to McDowell, human freedom consists in causations in the space of reason, but as Richard Gaskin points out, a satisfying story of it is yet to be provided. I close this essay with some rough ideas about how to fill in the details of the McDowellian picture. (shrink)

-- v. 3. Truth, knowledge, and modality.

Calling is a very important concept in Christianity. In the medieval era, calling was restricted to ecclesiastical work alone, a devotion to the life of contemplation. Ordinary work or physical labour was not considered qualified to be a calling. Martin Luther was the one who taught that the ordinary work of the ordinary people was also God’s calling and equally spiritual as the ecclesiastical work. However, Miroslav Volf, a Croatian theologian, criticised Luther that his view of calling was too static (...) and irrelevant to the modern context where people often choose to quit a job because of its negative effects and some people have to do multiple jobs in order to make ends meet. While recognising the validity of Volf’s critique, this article seeks to demonstrate that even in the modern context, calling is still a very important theological concept to reflect upon work. Luther’s vocational view of work could be retrieved in discussing the theology of work by putting it in dialogue with Calvin, Kuyper, and other theologians.Contribution: This article seeks to show that the concept of calling is indispensable in constructing a sound theology of work for the modern context. By understanding work as calling, Christian workers are enabled to see how they are participating in God’s redemptive work through their jobs. (shrink)

Introduction: Schools have become a primary setting for providing mental health care to youths in the U.S. School-based interventions have proliferated, but their effects on mental health and academic outcomes remain understudied. In this study we will implement and evaluate the effects of a flexible multidiagnostic treatment called Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems on students' mental health and academic outcomes.Methods and Analysis: This is an assessor-blind randomized controlled effectiveness trial conducted across five (...) school districts. School clinicians are randomized to either MATCH or usual care treatment conditions. The target sample includes 168 youths referred for mental health services and presenting with elevated symptoms of anxiety, depression, trauma, and/or conduct problems. Clinicians randomly assigned to MATCH or UC treat the youths who are assigned to them through normal school referral procedures. The project will evaluate the effectiveness of MATCH compared to UC on youths' mental health and school related outcomes and assess whether changes in school outcomes are mediated by changes in youth mental health.Ethics and Dissemination: This study was approved by the Harvard University Institutional Review Board. We plan to publish the findings in peer-reviewed journals and present them at academic conferences.Clinical Trial Registration:ClinicalTrials.gov ID: NCT02877875. Registered on August 24, 2016. (shrink)

_Zettel, _ an en face bilingual edition, collects fragments from Wittgenstein's work between 1929 and 1948 on issues of the mind, mathematics, and language.

Humanism, modernity, and scientific rationality are examined critically in these collected essays.

'The most thorough and scrupulous of contemporary students of induction' (the execrable Quinton 1993, p. 172).

Do the rich descriptions and narrative shapings of literature provide a valuable resource for readers, writers, philosophers, and everyday people to imagine and confront the ultimate questions of life? Do the human activities of storytelling and complex moral decision-making have a deep connection? What are the moral responsibilities of the artist, critic, and reader? What can religious perspectives—from Catholic to Protestant to Mormon—contribute to literary criticism? Thirty well known contributors reflect on these questions, including iterary theorists Marshall Gregory, James Phelan, (...) and Wayne Booth; philosophers Martha Nussbaum, Richard Hart, and Nina Rosenstand; and authors John Updike, Charles Johnson, Flannery O'Connor, and Bernard Malamud. Divided into four sections, with introductory matter and questions for discussion, this accessible anthology represents the most crucial work today exploring the interdisciplinary connections between literature, religion and philosophy. (shrink)

Descartes made a sharp distinction between matter and mind. But he also thought that the two interact with one another. Is such interaction possible, however, without either a materialist reduction of mind to matter or an idealist (phenomenalist) reduction of matter to mind? These questions overshadow the Western tradition in metaphysics from the time of Descartes to present times. The book makes an effort to stay clear of reductivist views of the two Cartesian substances. It defends a dualistic psycho-physical parallel (...) theory which reconciles freedom of action with determinism in nature. Basic problems in perception theory are also discussed, with special emphasis on hearing and sound. Because of the intrinsic interest of the subject and the author's non-technical presentation of it, the book should appeal to all readers with a serious interest in philosophy and psychology. (shrink)

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. (...) S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. (shrink)