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)

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)

Sustaining soil fertility is essential to the prosperity of many households in the mid-hills of Nepal, but there are concerns that the breakdown of the traditional linkages between forest, livestock, and cropping systems is adversely affecting fertility. This study used triangulated data from surveys of households, discussion groups, and key informants in 16 wards in eastern and western Nepal to determine the existing practices for soil fertility management, the extent of such practices, and the perception of the direction of changes (...) in soil fertility. The two principal practices for maintaining soil fertility were the application of farmyard manure (FYM) and of chemical fertilizer (mainly urea and diammonium phosphate). Green manuring, in-situ manuring, slicing terrace risers, and burning plant residues are rarely practiced. FYM usage was variable with more generally applied to khet land (average 6053 kg fresh weight manure ha−1) than to bari land (average 4185 kg fresh weight manure ha−1) with manure from goats and poultry preferred above that from cows and buffaloes. Almost all households (98%) apply urea to khet land and 87% to bari land, with 45% applying diammonium phosphate to both types of land. Application rates and timings of applications varied considerably both within and between wards suggesting poor knowledge transfer between the research and farming communities. The benefits of chemical fertilizers in terms of ease of application and transportation in comparison with FYM, were perceived to outweigh the widely reported detrimental hardening of soil associated with their continued usage. Among key informants, FYM applied in conjunction with chemical fertilizer was the most popular amendment, with FYM alone preferred more than chemical fertilizer alone – probably because of the latter’s long-term detrimental effects. Key informant and householder surveys differed in their perception of fertility changes in the last decade probably because of differences in age and site-specific knowledge. All key informants felt that fertility had declined but among households, only about 40% perceived a decline with the remainder about evenly divided between no change and an increase. Householders with small landholdings (< 0.5 ha) were more likely to perceive increasing soil fertility while those with larger landholdings (> 2 ha) were more likely to perceive declining fertility. Perceived changes in soil fertility were not related to food self-sufficiency. The reasons for the slow spread of new technologies within wards and the poor understanding of optimal use of chemical fertilizers in conjunction with improved quality FYM may repay further investigation in terms of sustaining soil fertility in this region. (shrink)

Colin Ward is not necessarily a gift for the biographer. As Sophie Scott-Brown’s engaging study reminds us, one of his defining characteristics was a thoroughgoing humility, and one consequence of...

Sophie Scott-Brown’s intellectual biography of Colin Ward does a superb job of putting Ward’s anarchism in its historical and political context. In so doing Scott-Brown arguably draws attention to how Ward’s pragmatic anarchism was dependent on post-war social democracy in the UK. This comment explores whether this makes Ward’s anarchism vulnerable in the following sense: that, as an anarchism, it cannot take sides in the struggle between social democracy and neo-liberalism even though its own prospects (...) for success depend on the strength of social democracy. Ward’s anarchism may be contrasted in this respect with libertarian/radical democratic socialisms (such as of Sheila Rowbotham and Stuart Hall) which envisage a simultaneous struggle both ‘for’ and ‘against’ the (social democratic) state. (shrink)

One of his obituarists describes Colin Ward (1924-2010) as ‘as one of the greatest anarchist thinkers of the past half century’, ‘a pioneering social historian’ and a chuckling anarchist.1 In the p...

Religion and the Rebel, Colin Wilson's second volume from his internationally acclaimed Outsider Cycle, is a casebook about and for rebels. With inspirational wisdom and engaging clarity, Wilson shows us that the purpose of religion, of our personal relationship with the sacred and the all-pervading mystery of existence, is to expand our consciousness and intensify our sense of life. Wilson heroically claims that the power to create meaning resides in our mental and spiritual discipline. Examining the lives and works (...) of Nietzsche, Kierkegaard, Rilke, Shaw, Pascal, Swedenborg, Rimbaud and Scott Fitzgerald, among others, Wilson explores the main existential questions and shows how these remarkable writers, scientists, philosophers and poets faced their need for transcendence. Like many of us, they were driven by a need to become more than men. Religion and the Rebel is an outstanding and enjoyable book that combines philosophical analysis, historical interest, and religious insight. (shrink)

Arguing for a new direction in postmodern theological thinking, away from the liberalism and nihilism of those who name themselves postmodern theologians, the ...

An important volume connecting classical studies with feminism, Feminism and Ancient Philosophy provides an even-handed assessment of the ancient philosophers' discussions of women and explains which ancient views can be fruitful for feminist theorizing today. The papers in this anthology range from classical Greek philosophy through the Hellenistic period, with the predominance of essays focusing on topics such as the relation of reason and the emotions, the nature of emotions and desire, and related issues in moral psychology. The volume contains (...) some new, ground-breaking essays on Plato, Aristotle, and the Stoics, as well as previously published pieces by established scholars like Martha Nussbaum and Julia Annas. It promises to be of interest to an interdisciplinary audience including those working in classics, ancient philosophy, and feminist theory. (shrink)

Discussions of sexual ethics often focus on the wrong of treating another as a mere object instead of as a person worthy of respect. On this view, the task of sexual ethics becomes putting the other’s subjectivity above their status as erotic object so as to avoid the harms of objectification. Ward and Anderson argue that such a view disregards the crucial, moral role that erotic objecthood plays in sexual encounters. Important moral features of intimacy are disclosed through the (...) experience of being an erotic object for another, as well as in perceiving another as an erotic object. Drawing on phenomenology, especially the insights of Simone de Beauvoir, Ward and Anderson argue that erotic encounters are shaped by the human condition of ambiguity, where being an object for others is intertwined with bodily agency. Because sexual agency is complex in this way, theories of sexual ethics and responsibility must widen their focus beyond transparent communication and authoritative expressions of will. (shrink)

Global Media Ethics is the first comprehensive cross-cultural exploration of the conceptual and practical issues facing media ethics in a global world. A team of leading journalism experts investigate the impact of major global trends on responsible journalism. The first full-length, truly global textbook on media ethics; Explores how current global changes in media promote and inhibit responsible journalism; Includes relevant and timely ethical discussions based on major trends in journalism and global media; Questions existing frameworks in media ethics in (...) light of the impact of global media; Contributors are leading experts in global journalism and communication. (shrink)

A short definitive account of Keith Ward's theology, based on the philosophy of Personal Idealism. It records Ward's views about God, revelation, the kingdom of God, life after death, the incarnation, atonement, and Trinity. In summary, it is a concise and clear account of most central Christian doctrines, formed in the light of modern science and Idealist philosophy.

Nietzsche distinguished between two forces in art: Apollonian, which represents order and reason, and Dionysian, which represents chaos and energy. Economists, Ward argues, have operated for too long under the assumption that their work reflects the scientific, Apollonian principals that inform physics when they simply do not apply to economics: 'constants' in economics stand in for variables, and the core scientific principles of prediction and replication are all but ignored by economists. Ward encourages economists to reintegrate the standard (...) rigor of the scientific method into their work while embracing the fact of the shape-shifting changeability of human beings. Economists can still aspire to scientific standards, as is demonstrated by the success of biology, in which there is considerable Dionysian variability. Economists must avoid the temptation to wish away dynamic complexity and diversity and must recognize, among other things, that the desire to take risks is fundamentally human. The second half of the book takes some first steps toward creating this new Dionysian Economics. (shrink)

Some of the series' finest lectures have been lost for many years, unavailable to the public in any form -- until now.

Some theories of goodness are descriptively rich: they have much to say about what makes things good. Neo-Aristotelian accounts, for instance, detail the various features that make a human being, a dog, a bee good relative to facts about those forms of life. Famously, such theories of relative goodness tend to be comparatively poor: they have little or nothing to say about what makes one kind of being better than another kind. Other theories of goodness—those that take there to be (...) absolute goodness—are comparatively rich: they offer grounds for judging some types of things better than others because they have more absolute goodness. Moorean accounts, for example, can tell us that humans and human experiences are superior to bees and blades of grass. But such theories tend to be descriptively poor: they struggle to tell us in virtue of what this is so. In this essay we motivate and flesh out a view that splits the difference between accounts of goodness as relative and accounts of goodness as absolute. Such a view holds promise only if the mechanics of this kind of metaphysics of goodness can be worked out. Here we present a view on which the paradigm for absolute goodness is God and the paradigm for each kind of relative goodness is a divine idea. (shrink)

'There is much food for thought in McGinn's discussions and each chapter is rich with a series of considerations for thinking that the currently received views on the various topics have some serious difficulties that need confronting... For those interested in metaphysics and the philosophy of logic, this book will stimulate much further thought' -Mind 'The sweep of the book is broad and the pace is brisk... There is much material here to provide the basis for many a deep philosophical (...) discussion' -Mind 'Lucid and provocative little book... clear, direct and well argued' -Times Higher Education SupplementIdentity, existence, predication, necessity, and truth are fundamental philosophical concerns. Colin McGinn treats them both philosophically and logically, aiming for maximum clarity and minimum pointless formalism. He contends that there are real logical properties that challenge naturalistic metaphysical outlooks. These concepts are not definable, though we can say a good deal about how they work. The aim of Logical Properties is to bring philosophy back to philosophical logic. (shrink)

The commentary argues that we cannot be sure that human consciousness has survival value and that in order to understand the origins and, perhaps, the function of consciousness, we should examine the behavioural and neural precursors to consciousness in nonhumans. An example is given of research on the role of context in decisions regarding fleeing from probable predators in the Mongolian gerbil.

In What the Body Commands, Colin Klein proposes and defends a novel theory of pain. Klein argues that pains are imperative; they are sensations with a content, and that content is a command to protect the injured part of the body. He terms this view "imperativism about pain," and argues that imperativism can account for two puzzling features of pain: its strong motivating power and its uninformative nature. Klein argues that the biological purpose of pain is homeostatic; like hunger (...) and thirst, pain helps solve a challenge to bodily integrity. It does so by motivating you to act in ways that help the body recover. If you obey pain's command, you get better. He develops his account to handle a variety of pain phenomena and applies it to solve a number of historically puzzling cases. Klein's intent is to defend the imperativist view in a pure form -- without requiring pain to represent facts about the world.Klein presents a model of imperative content showing that intrinsically motivating sensations are best understood as imperatives, and argues that pain belongs to this class. He considers the distinction between pain and suffering; explains how pain motivates; addresses variations among pains; and offers an imperativist account of maladaptive pains, pains that don't appear to hurt, masochism, and why pain feels bad. (shrink)

Colin Morris traces the origin of the concept of the individual, not to the Renaissance where it is popularly assumed to have been invented, but farther back, ...

The heart of this book is the reciprocal relationship between philosophical theories of mind and empirical studies of animal cognition.

Wittgenstein famously ended his Tractatus Logico-Philosophicus (Wittgenstein 1922) by writing: "Whereof one cannot speak, one must pass over in silence." (Wovon man nicht sprechen kann, darüber muss man schweigen.) In that earliest work, Wittgenstein gives no clue about whether this aphorism applied to animal minds, or whether he would have included philosophical discussions about animal minds as among those displaying "the most fundamental confusions (of which the whole of philosophy is full)" (1922, TLP 3.324), but given his later writings on (...) language and thought, it seems a plausible hypothesis. Years later he wrote in the Philosophical Investigations (1968, p. 223) another aphoristic statement: "If a lion could speak, we would not understand him." (Wenn der Löwe sprechen könnte, wir könnten ihn nicht verstehen.) Decades of philosophical discussion about what Wittgenstein meant by these remarks illustrate another point: when philosophers speak, we do not fully understand them. (shrink)

Many, including Marx, Rawls, and the contemporary 'Black Lives Matter' movement, embrace the ambition to secure terms of co-existence in which the worth of people's lives becomes a lived reality rather than an empty boast. This book asks whether, as some believe, the philosophical idea of human dignity can help achieve that ambition. Offering a new fourfold typology of dignity concepts, Colin Bird argues that human dignity can perform this role only if certain traditional ways of conceiving it are (...) abandoned. Accordingly, Bird rejects the idea that human dignity refers to the inherent worth or status of individuals, and instead reinterprets it as a social relation, constituted by affects of respect and the modes of mutual attention which they generate. What emerges is a new vision of human dignity as a vital political value, and an arresting vindication of its role as an agent of critical reflection on politics. (shrink)

This volume provides a guide to the discussion among biologists and philosophersabout the role of concepts such as function and design in an evolutionary understanding oflife.

This note motivates a logic for a theory that can express its own notion of logical consequence—a ‘syntactically closed’ theory of naive validity. The main issue for such a logic is Curry’s paradox, which is averted by the failure of contraction. The logic features two related, but different, implication connectives. A Hilbert system is proposed that is complete and non-trivial.

Research suggests that contact with nature can be beneficial, for example leading to improvements in mood, cognition, and health. A distinct but related idea is the personality construct of subjective nature connectedness, a stable individual difference in cognitive, affective, and experiential connection with the natural environment. Subjective nature connectedness is a strong predictor of pro-environmental attitudes and behaviors that may also be positively associated with subjective well-being. This meta-analysis was conducted to examine the relationship between nature connectedness and happiness. Based (...) on 30 samples ( n = 8523), a fixed-effect meta-analysis found a small but significant effect size ( r = 0.19). Those who are more connected to nature tended to experience more positive affect, vitality, and life satisfaction compared to those less connected to nature. Publication status, year, average age, and percentage of females in the sample were not significant moderators. Vitality had the strongest relationship with nature connectedness ( r = 0.24), followed by positive affect ( r = 0.22) and life satisfaction ( r = 0.17). In terms of specific nature connectedness measures, associations were the strongest between happiness and inclusion of nature in self ( r = 0.27), compared to nature relatedness ( r = 0.18) and connectedness to nature ( r = 0.18). This research highlights the importance of considering personality when examining the psychological benefits of nature. The results suggest that closer human-nature relationships do not have to come at the expense of happiness. Rather, this meta-analysis shows that being connected to nature and feeling happy are, in fact, connected. (shrink)

As arti® cial intelligence moves ever closer to the goal of producing fully autonomous agents, the question of how to design and implement an arti® cial moral agent (AMA) becomes increasingly pressing. Robots possessing autonomous capacities to do things that are useful to humans will also have the capacity to do things that are harmful to humans and other sentient beings. Theoretical challenges to developing arti® cial moral agents result both from controversies among ethicists about moral theory itself, and from (...) computational limits to the implementation of such theories. In this paper the ethical disputes are surveyed, the possibility of a `moral Turing Test ’ is considered and the computational di culties accompanying the diŒerent types of approach are assessed. Human-like performance, which is prone to include immoral actions, may not be acceptable in machines, but moral perfection may be computationally unattainable. The risks posed by autonomous machines ignorantly or deliberately harming people and other sentient beings are great. The development of machines with enough intelligence to assess the eŒects of their actions on sentient beings and act accordingly may ultimately be the most important task faced by the designers of arti® cially intelligent automata. (shrink)

In this paper, an evolutionary multiverse argument against naturalism (EMAAN) is presented: E1. In an evolutionary multiverse, phenomena have variable evolutionary ages. E2. After some time T, the development of the empirical sciences will be evolutionarily conserved. E3. The phenomena with an evolutionary age above T are methodologically supernatural. Entities are classified according to whether they are (1) physical and spatiotemporal, (2) causally efficacious, and (3) either observed by or explanatorily necessary for the empirical sciences. While the conjunction of (1) (...) and (2) is taken to be sufficient for existence in reality, the negation of (3) defines methodological supernaturalness. EMAAN uses a generalization of evolutionary theory, namely cosmological natural selection, to argue that phenomena evolve that fulfill conditions (1) and (2), but not (3). This shows that methodologically supernatural phenomena have a clear epistemology according to a theory that is grounded in the commitments of naturalism. Supernatural phenomena are not observed by the empirical sciences because the empirical sciences themselves are supernaturally guided and predestined to develop according to an evolutionarily conserved plan. In spite of this scientific plan, there is room for afterlives and supernaturality in the everyday experience. (shrink)

Logical consequence is the relation that obtains between premises and conclusion(s) in a valid argument. Orthodoxy has it that valid arguments are necessarily truth-preserving, but this platitude only raises a number of further questions, such as: how does the truth of premises guarantee the truth of a conclusion, and what constraints does validity impose on rational belief? This volume presents thirteen essays by some of the most important scholars in the field of philosophical logic. The essays offer ground-breaking new insights (...) into the nature of logical consequence; the relation between logic and inference; how the semantics and pragmatics of natural language bear on logic; the relativity of logic; and the structural properties of the consequence relation. (shrink)

Political philosophers have recently begun to take seriously methodological questions concerning what a theoretical examination of political ideals is suppose to accomplish and how effective theorising in ideal theory is in securing those aims. Andrew Mason and G.A. Cohen, for example, believe that the fundamental principles of justice are logically independent of issues of feasibility and questions about human nature. Their position contrasts sharply with political theorists like John Dunn and Joseph Carens who believe that normative theorising must be integrated (...) with an appreciation of the empirical realities of one’s society. Rather than bracket questions of feasibility and human nature, empirically-oriented political theorists believe that real, non- ideal considerations must be taken seriously when deriving normative theories of justice.1 And some justice-theorists, most notably John Rawls, attempt to. (shrink)

Recent work in philosophical logic has taken interesting and unexpected turns. It has seen not only a proliferation of logical systems, but new applications of a wide range of different formal theories to philosophical questions. As a result, philosophers have been forced to revisit the nature and foundation of core logical concepts, chief amongst which is the concept of logical consequence. This essay sets the contributions of the volume in context and identifies how they advance important debates within the philosophy (...) of logic. (shrink)

Nietzsche and Freud saw Christianity as metaphysical escapism, with Nietzsche calling the religion a "Platonism for the masses" and faulting Paul the apostle for negating more immanent, material modes of thought and political solidarity. Integrating this debate with the philosophies of difference espoused by Gilles Deleuze, Michel Foucault, Jacques Derrida, Jacques Lacan, and Pier Paolo Pasolini, Ward Blanton argues that genealogical interventions into the political economies of Western cultural memory do not go far enough in relation to the imagined (...) founder of Christianity. Blanton challenges the idea of Paulinism as a pop Platonic worldview or form of social control. He unearths in Pauline legacies otherwise repressed resources for new materialist spiritualities and new forms of radical political solidarity, liberating "religion" from inherited interpretive assumptions so philosophical thought can manifest in risky, radical freedom. (shrink)

The Socratic method is one of the timeless inventions of the ancient world. It is a path to wisdom and a way to think more intelligently about questions large or small. It is a technique for teaching others and for talking to yourself. It is an antidote to stupidity, to irrationality, and to social media. It is easy to understand but challenging to master. It is useful for everyone. This book explains the Socratic method in detail: what it is, where (...) it came from, and how to carry it out. The chapters teach the elements of the method step by step with examples from Plato's dialogues. They illustrate how to create Socratic questions of your own. They show how the teachings of Socrates produced the philosophies of Stoicism and Skepticism. The book also explains how the Socratic method can be put to work in the classroom, and it offers Socratic rules of engagement for talking about politics and other hard things. The Socratic Method is a complete guide to the practical use of a great idea. (shrink)