Here we review concepts related to an ensemble description of G-protein-coupled receptors. The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor, a prototypical class A GPCR. 19F Nuclear Magnetic Resonance studies show that apo A2AR is characterized by a broad ensemble of conformers, spanning inactive to active states, and resembling states defined earlier for rhodopsin. In keeping with (...) ideas associated with a conformational selection mechanism, addition of agonist serves to allosterically restrict the overall degrees of freedom at the G protein binding interface and bias both states and functional dynamics to facilitate G protein binding and subsequent activation. While the ligand does not necessarily “induce” activation, it does bias sampling of states, increase the cooperativity of the activation process and thus, the lifetimes of functional activation intermediates, while restricting conformational dynamics to that needed for activation. GPCRs represent a ubiquitous class of transmembrane receptors, responsible for cell signaling and cell homeostasis. Their activation gives rise to conformational changes that allow the receptor to engage downstream partners. Activation can be thought of in terms of a free energy landscape associated with distinct conformers, responsible for the process. Here, the action of ligands is seen to alter this landscape by enabling transitions between key intermediates. (shrink)

“The world of life which is comprised of the lithosphere, the hydrosphere and the atmosphere”: this definition of the biosphere is not complete since it does not express the determining influence of living organisms on its composition, on its structure and on the processes of its continuing evolution. The part of living matter in the biosphere is relatively small (about 0.25%), but this part has a considerable influence on its structure.The biosphere should be considered as the universal source of all (...) food products without exception. Mankind's ability to feed itself depends on the productivity of this biosphere in the first place. Moreover, its condition determines not only the quantity but also the quality of nourishment. The problem is a critical one today because of the increasing pollution of the biosphere by products poured into it by various human activities. (shrink)

The article examines the surprising role of Rousseau in the revival of liberal and humanist thought in contemporary French political thought. The choice of Rousseau as an inspiration and source of humanism is an illuminating indication of a shift in French thought. The authors concentrate on the natural- rights republicanism of Luc Ferry and Alain Renaut and the critical humanism of Tzvetan Todorov. While these thinkers all appeal to Rousseau's definition of humanity in terms of freedom, they draw on different (...) aspects of his thought and his relationship to the philosophic tradition. Their different receptions of Rousseau reveal tensions in the humanist revival and provoke reflection on the relationships among republicanism, liberalism and humanism in contemporary France. (shrink)

ABSTRACTIn this essay, I defend sport as a hobby in contrast to sport as a ‘mutual quest for excellence through challenge’. With the assistance of ideas found in the novel Don Quixote, I rai...

ABSTRACTIn this essay, I defend sport as a hobby in contrast to sport as a ‘mutual quest for excellence through challenge’. With the assistance of ideas found in the novel Don Quixote, I rai...

Religion has surprised the secular elites of North American and European societies. Not only has religion survived the treacherous passage from village to metropolis, from medieval superstition to modern science, and from state support (and coercion) to voluntary membership. Apparently, it has thrived and gained new sources of strength amidst these transformations. Far from being relegated to the proverbial ash‐heap of history, modern religions and the activist movements they generate find themselves positioned at the centre of modern debates – and (...) modern wars – over territory, political sovereignty, human rights, global and local economy, scientific research and popular culture. Among these activist movements, the most virulent and sustained are ‘fundamentalisms’ – increasingly sophisticated reactions against secular modernity that seek to fight back against the enemies of traditional religion by constructing religiously inspired and quintessentially modern alternatives to ‘godless’, idolatrous governments, institutions and political and cultural elites. (shrink)

The article is intended to reveal important similarities between fiction and sport. I build on Jonathan Gottschall’s discussion in The Storytelling Animal: How Stories Make Us Human by celebrating the significance of stories and their ‘witchy power’ and by examining factors that demonstrate similarities between fiction and sport. I suggest that an unmistakable semantic, structural, and cultural kinship exists between the two. This argument requires a discussion of play theory, play resources and constitutive rules, the semantic power of problems and (...) the uncertainty they produce, and the role of ‘frames’ in bringing problems to life. I conclude by noting the unique frame capabilities of ‘the big game’ and zero-sum dichotomous sporting motifs. (shrink)

This article looks at social entrepreneurs that operate for-profit and internationally, offering that international for-profit social entrepreneurs (IFPSE) are of a unique type. Initially, this article utilizes the entrepreneurship, social entrepreneurship, and international entrepreneurship literatures to develop a definition of the IFPSE. Next, a proposed model of the IFPSE is built utilizing the dimensions of mindset, opportunity recognition, social networks, and outcomes. Case studies of three IFPSE are then used to examine the proposed model. In the final section, findings from (...) the case studies are used to examine the proposed model and more fully elucidate the dimensions of the IFPSE. (shrink)

If educators are to educate they must be accorded some level of trust. Anthony Giddens claims that because trust is not easily created, it is now being replaced with ‘confidence’ because this latter disposition is much easier to give and is more convenient. It is argued in this paper that this shift from trust to confidence stifles education because emphasis is placed solely upon qualifications and competence, and is neglectful of disclosing one’s motives and desires—which are considered to be essential (...) elements for relationships and communities which depend upon trust. Therefore, educators ought to seek to become more trustworthy by going beyond evidence-based practices and codes of ethics, towards articulating a developed personal philosophy of education outlining the ultimate end-purposes to which they aspire. Through such a philosophy, educators identify their ultimate desires and commitments and this self-disclosure can make trust-giving more likely. Demonstrated evidence of achievements and qualifications encourage confidence and this has some value. In addition to these artefacts of evidence, it is argued here that educators must also articulate what they actually desire. This can be understood as John Dewey’s virtue of ‘genuine interest’ which he characterises as being wholehearted, persistent and impartial. For educators, this is often represented in our personal philosophy of education and because it is personal, it is also existential in the sense that it pertains to giving sense, meaning and purpose to all of our activities and way of life for which we are individually responsible and passionately committed to as professionals. As a consequence of being existential, our philosophy and our commitment to it has an intellectual and moral aspect and because it reaches to the very depths of our raison d’être, it pertains to our passion as described by Søren Kierkegaard. This paper shall draw upon Dewey’s notion of wholeheartedness and Kierkegaard’s notion of purity of heart, to make the case that if educators embrace these in their practices, we may become more trustworthy. (shrink)

The dominance of capitalism, through the hegemony of neoliberal ideology, is maintained as an illusion through the use of four main strategies. In order to obtain the consent of the population, mass schooling tends to produce graduates who accept this illusion because they are vulnerable to these strategies and cannot imagine a post-capitalist world. However, through education, people can better appreciate the problematic reality of unbridled capitalism, such as the degradation of the global ecosystem. It is argued here that programs (...) which are designed to address these problems, such as Education for Sustainable Development, are dependent upon citizens developing a critical consciousness. This consciousness is firstly able to confront the four strategies maintaining capitalism’s dominance. It is argued that an education which engages with spiritual ideals and values regarding how a good life is understood in an aspirational sense, enables people to engage with the dominance of capitalism and to envision other possibilities for society in which capitalism is harnessed to serve the greater public good. This requires education’s ontology – as the character of students – to critically read the world, imagine possibilities which can constitute a good life, and are courageous to enact the social actions required to make these ideals a reality. This is made possible by an education which returns to the spiritual roots of ideals. (shrink)

In this essay, I revisit my claims about game structures and amend them by adding achievement-regulated games to previously analyzed time- and event-structured activities. In describing achievement formats, I discuss their heavy reliance on the world of work, their strong dependency on Suits’ lusory attitude, and their relative independence from constitutive rules. I argue that achievement-structured games carry disadvantages not shared by time- and event-regulated activities. I speculate that achievement gaming came first in our evolutionary history, but show that it (...) still holds value for modern players and spectators. (shrink)

In this analysis, I employ Husserl’s three-part description of intentionality to show how a player/play act/play object model for consciousness helps us see play more clearly. I review Suits’ logic-based attempts to amend Huizinga’s overly inclusive characterization of play. However, I do so on what I see as stronger phenomenological grounds by describing four kinds of experience embedded in Suits’ work-play dichotomy. I analyze two species of play-fortified work – namely, work that requires intrinsic enhancement and work that does not. (...) I also describe two species of play – namely, play that is compromised and play that is unfettered. I conclude by summarizing advantages of phenomenological analyses and underlining the important distinctions this philosophic method uncovers within traditional work and play categories. (shrink)

In industries populated by small and medium enterprises, managers' good intentions frequently incur barriers to superior environmental performance (Tilley, Bus Strategy Environ 8:238-248, 1999). During the period when the U.S. wine industry was beginning to promote voluntary adoption of sound environmental practices, we examined managers' attitudes, norms, and perceptions of stakeholder pressures to assess their intentions to implement environmental management programs (EMP). We found that managers within the simple structures of these small and medium firms are responsive to attitudes, norms, (...) and pressures from internal stakeholders and that voluntarily established EMP increased the success of firms' implementation of energy conservation and recycling practices. Applications of our findings to future research on small and medium enterprises as well as direct practical applications of our results are discussed. (shrink)

The development of the science of economics is closely linked to the structure of capitalism. Even though ancient and medieval thinkers had already stated a certain number of ideas in this domain, the science of economics, in the modern sense of the word, did not truly begin until the 17th Century and the early 18th Century. At that time the methodology for research in the natural sciences was developed, and the first scientific academies and societies were founded (England, France, Prussia, (...) Russia). The initial step in the development of the science of economics occurred in conjunction with this process. Moreover, the ideas of the first economists were, as a general rule, centered on the practical problems and needs of the State. And in that period the prevalent state structure in Europe was the absolute monarchy. Consequently, the first economists were, for the most part, counsellors to the sovereign, authors of studies and reports containing a variety of proposals regarding economic policy. With regard to a great many distinguished economists of the 17th and 18th Centuries, we can speak of them being “men of proposals”. (shrink)

Over the past three centuries in the West, there has been a sort of oscillation between two antagonistic visions of the world. One sees the world as being fundamentally inert, in such a manner that all hopes, dreams and technological delights are permitted. The other thinks of the world as inhabited by a spirit who consecrates all its parts by recording them in a great whole. We can think of the pantheism that sets itself in opposition to Newton's materialism or, (...) more exactly, to the materialist interpretation given to Newton in the 18th century. In the 17th century the opposite had occurred. The magic universe of the Renaissance had given place to the triumphs of the Cartesian mechanism. As for protestantism, which is said to have been one of the most powerful factors of disenchantment after the 17th century, how was one not to see it prolonged, by reaction, into a philosophy for which nature is the tangible presence of God? When Calvin wrote that nothing happens in nature that is not a direct effect of the divine will, we already see appear in the background the mystic ecstasies that Rousseau experienced in nature. For if no single leaf flutters and no breeze blows without divine intervention, then receiving the slightest sensation would mean, according to Jean-Jacques Rousseau, entering into direct contact with God. (shrink)

It is with these virile words of the Martinique poet Aimé Сésaire, an expression of assurance regained, testimony to a self-confidence once stolen but then reconquered, that I would like to open my remarks.*Africa was present at the last great international philosophical meeting two years ago in Montreal. I would like here to illustrate the meaning behind this presence and to explain the reasons why we wanted to be present, in order to avoid facile misunderstandings which could have weighty consequences.

Volume I. Metaphysics and sport -- volume II. Ethics of sport -- volume III. Sport and the good life -- volume IV. Sport and education.

Volume 47, Issue 2, July 2020, Page 318-321.

Traditionally genetics is said to be the science of heredity. At least this was how William Bateson defined it in 1906. Today this is no longer the case. Since about ten years ago. when biologists learned to extract genes from cells, to transfer them from cell to cell, to dissect them, to analyze them biochemically, in short to manipulate them, the term genetics has tended rather to designate the science of the action of genes in cells. (This is what was (...) formerly called physiological genetics). In any case this is the form of genetics which today is in the forefront of biological research. (This is also called molecular genetics). This kind of genetics is also in the forefront in the media, because of its present or potential applications, in the realms of biotechnology, genetic therapy and so on. (shrink)

In our times changes occur so rapidly that our modes of reading even more than our modes of analysis risk being inadequate, or in any case risk lagging behind. If we wish to analyze relations between the arts and the media, the danger is in fact that we will limit ourselves to established notions or even to stereotypes which are commonly accepted by the general public. Even for persons with some awareness, information remains lacunary. Moreover, like the experts, or those (...) who pass for such, it seems that it is difficult for them to avoid a personal conception, implicit or avowed, which does not fail to influence their judgement. This is almost always the case when the matter of art is raised, even if we take the precaution of placing the term in the plural. Whether one wishes to or not, there is hardly an example where certain preferences do not make themselves known. If it is easy to reach agreement with regard to the facts, it is less easy to agree on their interpretation, especially when values are at stake. Hence the necessity to proceed by different steps and explanations to explain the relationships between arts and the media. (shrink)

The purpose of this article is to attempt to discern better the situation of art in contemporary society. To do this we will examine essentially the exterior forces which influence it. These multiple and diverse evolutionary forces are in a certain manner centripetal, and ultimately they modify our concepts of art as such. Without going so far as to state that contemporary society has completely overturned our ideas on this question, signs of change are nevertheless visible which challenge fundamental characteristics (...) up until now attributed to art. (shrink)

The terms “modem” and “modernity”, like many other terms in common use and of wide extension, are extremely complex. And a theory of modernity should have no other goal initially than to settle this polysemy in the hope of arriving at a sufficiently rigid definition that the “thing” itself can become the object of a clearer consideration. But what is the path toward this greater clarity?

It is some 900 years before Christ that we find the most ancient traces of two innovations which were to have incalculable consequences for the future of mankind. The evolution of civilization has, in fact, been marked by a clean break located at the era when man discovered the rudiments of agriculture and animal husbandry and began to produce his own food. Whereas for the three million years during which he had to provide for his needs exclusively through hunting, fishing (...) and gathering, his progress was extremely slow, the adoption of a new way of life based on agriculture and animal husbandry allowed man to transform himself in less than twelve thousand years from deer hunter into astronaut. (shrink)

One of the dominant characteristics of Western philosophical and literary history of the last two centuries is that the object of desire (in the novel) and the object of perception (in epistemology) have been made to reveal aspects which are more complex than the classical age had suspected. With Descartes, everything was clear: the object is but a portion of extension. But with Kant things already become more complicated: the object has a mysterious. en-soi (an sich-in itself) which escapes us. (...) And the object of desire, in literature, acquires such a mystic character that it loses its status of creature. “For what the romantic lover seeks is not really the beloved”, writes Eric Heller. “Intermingled with his erotic craving, inarticulate, diffuse, and yet dominating it, is the desire for spiritual salvation.” It is no longer the object (the creature) which one wishes to embrace, but the invisible reality mirrored in it. Desire does not tend so much toward objects as toward what lies beyond these objects where, it believes, it will find its salvation. (shrink)

If we attempt to unify the theoretical efforts that appreciate a specific social activity in play, we can sketch the perspective of an entire anthropology of play into cohesive parts deriving from the knowledge of collective experience. This preoccupation is, in fact, two-fold. On the one hand is the comprehensive description of the relationship between life styles and their stylizations in everyday practices and customs as well as in cultural works, and on the other are social sensitivities and representations that (...) are relatively shared by individuals grouped in human communities. This very general framework encourages situating the presence of play as one of the concrete manifestations of an emotional core, converting primitively negative impulses into attractive forces which, because of this, becomes the seat of all human interaction and agitation, the energetic heart of social power. (shrink)

At first glance, the formulation of the principle of inertia—not. yet complete with Galileo, more precise with Gassendi, finally systematic with Newton—seems to constitute but one of the aspects of a process of deep transformations at the end of which traditional cosmology was replaced by various world systems. These transformations—or, to use a more classic term, this “ scientific revolution” —have been the object of numerous works, a list, of which would alone fill the pages of a thick volume. But (...) the principle of inertia itself, a principle about which can be said without exaggeration that it expressed the essence of this revolution at the same time as it stimulated it, has perhaps not received all the attention it deserves. And especially the impact of this principle on Western culture has not been fully measured. True, Alexandre Koyré has always insisted on the fact that, by reducing movement to a state like that of the state of rest, the principle of inertia expressed a new vision of the world more than a scientific result. But his admirable analyses deal more with the slow advent of the priciple of inertia among the natural philosophers who preceded, accompanied and then followed Galileo than with the theological, philosophical and literary impact of this principle. Moreover, by examining this impact, we discover that it is necessary to make a distinction between Euclidian space and absolute space, a distinction which is frequently implicit with certain scientific historians, but, and this must be emphasized, is more often ignored. (shrink)

Though nominalism is a major presupposition in academia and western society, R. Scott Smith shows that nominalism undermines all knowledge whatsoever. In light of the many clear examples of knowledge that we do have, nominalism should be replaced by a realist view of properties.

For most of the church's history, people have seen Christian ethics as normative and universally applicable. Recently, however, this view has been lost, thanks to naturalism and relativism. R. Scott Smith argues that Christians need to overcome Kant's fact-value dichotomy and recover the possibility of genuine moral and theological knowledge.