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...

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...

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)

Plato’s Theaetetus, Sophist, and Statesman exhibit several related dialectical methods relevant to Platonic education: maieutic in Theaetetus, bifurcatory division in Sophist and Statesman, and non-bifurcatory division in Statesman, related to the ‘god-given’ method in Philebus. I consider the nature of each method through the letter or element paradigm, used to reflect on each method. At issue are the element’s appearances in given contexts, its fitness for communing with other elements like it in kind, and its own nature defined through its (...) relations to others. These represent stages of inquiry for the Platonic student inquiring into the sources of knowledge. (shrink)

Throughout her work, Audre Lorde maintains that her self-preservation in the face of oppression depends on acting from the recognition and valorization of her feelings as a deep source of knowledge. This claim, taken as a portrayal of agency, poses challenges to standard positions in ethics, epistemology, and moral psychology. This article examines the oppositional agency articulated by Lorde’s thought, locating feeling, poetry, and the power she calls “the erotic” within her avowed project of self-preservation. It then explores the implications (...) of taking seriously Lorde’s account, particularly for theorists examining ethics and epistemology under nonideal social conditions. For situations of sexual intimacy, for example, Lorde’s account unsettles prevailing assumptions about the role of consent in responsibility between sexual partners. I argue that obligations to solicit consent and respect refusal are not sufficient to acknowledge the value of agency in intimate encounters when agency is oppositional in the way Lorde describes. (shrink)

In this chapter I explore the reciprocal relationship between the metaphysical views mathematicians hold and their mathematical activity. I focus on the set-theoretic pluralism debate, in which set theorists disagree about the implications of their formal mathematical work. As a first case study, I discuss how Woodin’s monist argument for an Ultimate-L feeds on and is fed by mathematical results and metaphysical beliefs. In a second case study, I present Hamkins’ pluralist proposal and the mathematical research projects it endows with (...) relevance. These case studies support three claims: (1) the metaphysical views of mathematicians can shape what counts as relevant research; (2) mathematical results can shape the metaphysical beliefs of mathematicians; (3) metaphysical thought and mathematical activity develop in tandem in mathematical practices. This makes metaphysical thought an integral part of mathematical practices. (shrink)

Introduction: Conversion and the practice of transformation -- The philosophical structure of Jonathan Edwards's religious affections -- Habit, habit change, and conversion in C.S. Peirce -- Reconstructing faith : religious overcoming in Dewey's pragmatism -- Transforming obligation in William James -- Dwelling in absence: the reflective origin of conversion -- Creative transformation : the work of conversion -- The evasion of conversion in recent American philosophy.

In Plato’s Statesman, the Eleatic Stranger leads Socrates the Younger and their audience through an analysis of the statesman in the service of the interlocutors’ becoming “more capable in dialectic regarding all things”. In this way, the dialectical exercise in the text is both intrinsically and instrumentally valuable, as it yields a philosophically rigorous account of statesmanship and exhibits a method of dialectical inquiry. After the series of bifurcatory divisions in the Sophist and early Statesman, the Stranger changes to a (...) non-bifurcatory method of dividing to account for the statesman, but does not explain the reason for this change. I argue that the change is prepared by the elements discussed in the digression from 277a2 to 287b2. Here the Stranger makes use of four concepts that are crucial for understanding this change: the notion of paradigm, the paradigms of care and the weaver, and the notion of due measure. I claim that the notion of paradigm clarifies the nature of dialectical inquiry, care and weaving act as paradigms appropriate to dialectical practice, and an account of due measure offers insight into the constitutive ratios that govern the structuring of kinds pursued through dialectical inquiry. I suggest that the non-bifurcatory method is intended to articulate knowledge in the strictest sense, or knowledge of the forms, presenting a method of inquiry into being and its structure that will foster the turning of the soul from things to forms that Socrates describes in the Republic. (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.

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)

The British Idealist movement flourished between the 1860s and 1920s and exerted a very significant influence in the USA, India and Canada, most notably on John Dewey and Josiah Royce. The movement also laid the groundwork for the thought of Oakeshott and Collingwood. Its leading figures – particularly Green and Caird – have left a number of complete or near complete manuscripts in various British university archives, many of which remain unpublished. This important collection widens access to this unpublished material (...) by transcribing, editing and then publishing the most significant pieces. The project focuses on the moral, political, and religious writings – the areas of most interest to scholars. This annotated, critical edition opens them up to the academic community. (shrink)

Here I interpret a central passage in Plato's Sophist by focusing on understudied elements that provide insight into the fit of the dialogue's parts and the Sophist-Statesman diptych as a whole. I argue that the Eleatic Stranger's account of what the dialectician "adequately views" at Sophist 253d1-e3 involves both division and the communion of ontological kinds, not just one or the other as has been typically argued. I also consider other key passages and the turn throughout the dialogue from imagistic (...) opining toward noetic understanding. (shrink)

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

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)

A dominant strand of philosophical thought holds that natural kinds are clusters of objects with shared properties. Cluster theories of natural kinds are often taken to be a late twentieth-century development, prompted by dissatisfaction with essentialism in philosophy of biology. I will argue here, however, that a cluster theory of kinds had actually been formulated by William Whewell (1794-1866) more than a century earlier. Cluster theories of kinds can be characterized in terms of three central commitments, all of which are (...) present in Whewell’s work on classification. Like contemporary cluster theorists, Whewell claims that kinds are united by similarity, that many kinds do not have essences, and that there are “gaps” between kinds. Moreover, Whewell advises taxonomists to look for consilience (roughly, convergence) between different classificatory schemes, a recommendation that reinforces the identification of natural classes with property clusters. Thus Whewell was not only an early cluster theorist, but one with important insights into what a cluster theory of kinds means for the practice of classification. (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)

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)

Distributive justice decision making tends to require a trade off between different valued outcomes. The present study tracked computer mouse cursor movements in a forced-choice paradigm to examine for tension between different parameters of distributive justice during the decision-making process. Participants chose between set meal distributions, to third parties, that maximised either equality (the evenness of the distribution) or efficiency (the total number of meals distributed). Across different formulations of these dilemmas, responding was consistent with the notion that individuals tend (...) to base decisions in part on the magnitude of these parameters. In addition, dilemmas associated with inconsistent responding across the sample tended to elicit the greatest spatial deviation of the cursor, potentially reflecting dilemma difficulty. One interpretation of these results is that individuals value equality and efficiency in such a way that moral dilemmas are resolved by comparing the perceived value of these qualitatively different parameters, consistent with a value pluralistic framework of decision making. A post-hoc analysis indicated that individuals also incorporated sufficiency concerns during distributive justice decision making. The results are discussed in relation to political philosophy. (shrink)

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)

This article proposes the comparison of two methods of analysis, semiotics, and hermeneutics, to address contemporary issues in ethical and political philosophy, through the study of the phenomenon of epistemic injustice. Conceptualized by Fricker (2007), epistemic injustice is synonymous with the denial of the value of knowledge that an individual possesses because of prejudices about the social group to which he or she belongs or is affiliated. When epistemic injustice is studied in the empirical world, it poses some crucial issues (...) in terms of interpreting the meaning that the individual gives to the experience of injustice that he or she experiences. Although the interpretation of injustice is central to the understanding of the phenomenon itself, little research in ethical and political philosophy addresses these aspects, because of the failure to sufficiently mobilize analytical methods such as semiotics and hermeneutics. However, these two methods, usually used in other fields to deal with these aspects, allow us to question the treatment and the interpretative scope of the epistemic injustice by the different interlocutors involved in the interaction in which it is reconducted. The comparison of these two methods in the analysis of epistemic injustice finally allows us to argue in favor of the hermeneutic method, as defined by Gadamer and rethought by Code (2003), to enhance Gadamer's legacy through the analysis of ethical and political issues in human sciences research. (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)

(2013). Life, the Unhistorical, the Suprahistorical: Nietzsche on History. International Journal of Philosophical Studies: Vol. 21, No. 1, pp. 64-91. doi: 10.1080/09672559.2012.744532.

What is it to be an agent? One influential line of thought, endorsed by G. E. M. Anscombe and David Velleman, among others, holds that agency depends on practical rationality—the ability to act for reasons, rather than being merely moved by causes. Over the past 25 years, Velleman has argued compellingly for a distinctive view of agency and the practical rationality with which he associates it. On Velleman’s conception, being an agent consists in having the capacity to be motivated by (...) a drive to act for reasons. Your bodily movements qualify as genuine actions insofar as they are motivated in part by your desire to behave in a way that makes sense to yourself. However, there are at least two distinct ways of spelling out what this drive towards self-intelligibility consists in, both present in Velleman’s work. It might consist in a drive towards intelligibility in causal-psychological terms: roughly, a drive to maximize the rational coherence of your psychological states. Alternatively, it might consist in a drive towards narrative intelligibility: a drive to make your ongoing activity conform to a recognizable narrative structure, where that structure is understood emotionally. Velleman originally saw these options as basically equivalent, but later came to prioritize the drive towards causal-psychological intelligibility over that towards narrative intelligibility. I argue that this gets things the wrong way round—we should instead understand our capacities to render ourselves intelligible in causal-psychological terms as built upon a bedrock of emotionally suffused narrative understanding. In doing so, we resolve several problems for Velleman’s view, and pave the way for an embodied, embedded and affective account of practical rationality and agency. According to the picture that emerges, practical rationality is essential to agency, narrative understanding is essential to practical rationality, and the rhythms and structures patterning the ebb and flow of our emotional lives are essential to narrative understanding. (shrink)

I here revive and support the hypothesis that Plato's Cratylus is set in 399 BCE, on the day of the Theaetetus and Euthyphro and before that of the Sophist and Statesman. To revive it, I suggest that the competing cases for other dramatic dates are weaker. To support it, I show that the connections between the Cratylus and Euthyphro warrant reconsideration, and I consider neglected dramatic details, the role of etymology in religious esotericism, and some missed connections between the philosophical (...) concerns of the two dialogues. I conclude by suggesting ways in which this hypothesis yields promising new horizons to explore. (shrink)

Nietzsche was a philosopher who prided himself, in deliberate contradistinction with previous philosophers, on his ‘historical sense’. But this leaves many questions unanswered about the precise role of the historical in Nietzsche’s philosophy. Perhaps most importantly, can the conception of genealogy in Nietzsche’s later philosophy, as a revised historical method, be taken to represent his mature philosophical methodology in general? I argue, firstly, that there is considerable continuity between Nietzsche’s conceptions of history in the early essay ‘On the uses and (...) disadvantages of history for life’ and those of his later philosophy. The former can therefore be used as a resource for understanding the latter. Through a reading of the early history essay I demonstrate that Nietzsche’s conception of the historical here is intimately bound up with the notion of the ‘unhistorical’ and that it is precisely renewed access to the unhistorical which is required in order for history to be conducive to the flourishing of humanity. I go on to contend that this holds for Nietzsche’s later writings as well, and that genealogy, being purely historical, must therefore be seen as one subsidiary part of a broader philosophy in which the unhistorical will play, literally, a vital role. (shrink)

Many weaknesses of game theory are cured by new models that embody simple cognitive principles, while maintaining the formalism and generality that makes game theory useful. Social preference models can generate team reasoning by combining reciprocation and correlated equilibrium. Models of limited iterated thinking explain data better than equilibrium models do; and they self-repair problems of implausibility and multiplicity of equilibria.

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.