G protein‐coupled receptors (GPCRs) are the largest family of transmembrane receptors and primarily signal through two main effector proteins: G proteins and β‐arrestins. Many agonists of GPCRs promote “biased” responses, in which different cellular signaling pathways are activated with varying efficacies. The mechanisms underlying biased signaling have not been fully elucidated, with many potential “hidden variables” that regulate this behavior. One contributor is “location bias,” which refers to the generation of unique signaling cascades from a given GPCR depending upon the (...) cellular location at which the receptor is signaling. Here, we review evidence that GPCRs are expressed at and traffic to various subcellular locations and discuss how location bias can impact the pharmacologic properties and characterization of GPCR agonists. We also evaluate how differences in subcellular environments can modulate GPCR signaling, highlight the physiological significance of subcellular GPCR signaling, and discuss the therapeutic potential of exploiting GPCR location bias. (shrink)

Fundamental questions in value sensitive design include whether and how high-tech products/artefacts could embody values and ethical ideals, and how plural and incommensurable values of ethical and social importance could be chosen rationally and objectively at a collective level. By using a humanitarian cargo drone study as a starting point, this paper tackles the challenges that VSD’s lack of commitment to a specific ethical theory generates in practical applications. Besides, it highlights how mainstream ethical approaches usually related to VSD are (...) incapable of solving main ethical dilemmas raised by technological design for well-being in democratic settings. Accordingly, it is argued that VSD’s ethical-democratic import would substantially be enhanced by the espousal of a procedural ethics stance and the deliberative approach to value and welfare entailed by Amartya Sen’s capability approach. Differently from rival ethical–political theories, its normative and meta-ethical foundations better handle human diversity, value-goal pluralism, conflicting vested interests as well as the epistemic-moral disagreements typical of contemporary complex democracies. Particularly, Sen’s capability approach procedural-deliberative tenets result in an “objective-impartial” choice procedure selecting a “hierarchy” of plural incommensurable values and rational goals thus, suitable to validate an applied science such as welfare-oriented technological design in concrete social environments. Conclusions suggest that refining VSD with a capability-based procedural approach to ethics fosters the concern for democracy and social justice while preserving vital scientific-technical standards. Major advantages are at an applied level to delivering ethically and socially justified, but yet highly functional technologies and high-tech products/artefacts. (shrink)

Contemporary suicide terrorists from the Middle East are publicly deemed crazed cowards bent on senseless destruction who thrive in poverty and ignorance. Recent research indicates they have no appreciable psychopathology and are as educated and economically well-off as surrounding populations. A first line of defense is to get the communities from which suicide attackers stem to stop the attacks by learning how to minimize the receptivity of mostly ordinary people to recruiting organizations.

In his early lecture courses, Martin Heidegger exhibited an abiding interest in human life. He believed that human life has philosophical import while it is actually being lived; language has philosophical import while it is being spoken. In this book, Scott Campbell traces the development of Heidegger's ideas about factical life through his interest in Greek thought and its concern with Being. He contends that Heidegger's existential concerns about human life and his ontological concerns about the meaning of Being (...) crystallize in the notion of Dasein as the Being of factical human life. Emphasizing the positive aspects of everydayness, Campbell explores the contexts of meaning embedded within life; the intensity of average, everyday life; the temporal immediacy of life in early Christianity; the hermeneutic pursuit of life's self-alienation; factical spatiality; the temporalizing of history within life; the richness of the world; and the facticity of speaking in Plato and Aristotle. He shows how Heidegger presents a way of grasping human life as riddled with deception but also charged with meaning and open to revelation and insight. (shrink)

The treatment in what follows of the politics of hegemony is not per se one of Gramsci, or Laclau or of Stuart Hall's earlier work. At stake is something that encompasses a more general regime of power that will be developed throughout the length of this: what might be called 'extensive politics'. What I will try to show is that such extensive power or such an extensive politics is being progressively displaced by a politics of intensity. I will trace the (...) shift from hegemony or extensive politics to such an intensive politics in terms of: 1) a transition to an ontological regime of power, from a regime that in important respects is 'epistemological', 2) a shift in power from the hegemonic mode of 'power over' to an intensive notion of power from within and power as generative force, 3) a shift from power and politics in terms of normativity to a regime of power much more based in what can be understood as a 'facticity'. This points to a general transition from norm to fact in politics. From hegemonic norm to what we will see are intensive facts. The fourth section will look at this shift through a change from an extensive regime of representation to an intensive regime of communications. (shrink)

Since the Middle Ages, Aristotle has been hailed as the father of economics. But recently classicists have maintained that he did no economics at all. This book clears up the anomaly. The author argues that Aristotle had a theory of money and commerce, but that it is ethical rather than economic. According to Aristotle ethics and economics are fundamentally opposed and can never be reconciled.

Science and the originality of life -- Christian facticity -- Grasping life as a topic -- Ruinance -- The retrieval of history -- Facticity and ontology -- Factical speaking -- Rhetoric -- Sophistry.

Richard Thaler and Cass Sunstein, in Nudge: Improving Decisions About Health, Wealth, and Happiness, assert that rejecting the use nudges is ‘pointless’ because ‘[i]n many cases, some kind of nudge is inevitable’. Schlomo Cohen makes a similar claim. He asserts that in certain situations surgeons cannot avoid nudging patients either toward or away from consenting to surgical interventions. Cohen concludes that in these situations, nudging patients toward consenting to surgical interventions is uncriticizable or morally permissible. I call this argument: The (...) Unavoidability Argument. In this essay, I will respond to Cohen's use of the unavoidability argument in support of using nudges during the process of informed consent. Specifically, I argue that many so-called ‘unavoidable nudges’ are, in fact, avoidable. Although my argument is directed toward Cohen's use of the unavoidability argument, it is applicable to the unavoidability argument more generally. (shrink)

BackgroundDelirium is highly prevalent in the general hospital patient population, characterized by acute onset, fluctuating levels of consciousness, and global impairment of cognitive functioning. Mental capacity, its assessment and subsequent consent are therefore prominent within this cohort, yet under-explored.AimThis study of patients with delirium sought to determine the processes by which consent to medical treatment was attempted, how capacity was assessed, and any subsequent actions thereafter.MethodA retrospective documentation review of patients identified as having a delirium for the twelve months February (...) 2013 to January 2014 was undertaken. Inclusion and exclusion criteria were used; demographic and descriptive data collected. A total of n=1153 patients were identified with n=310 meeting inclusion criteria.ResultA random sample of one hundred patients were subsequently reviewed. One third of patients had documentation relating to consent, while four patients had documentation relating to capacity. Median delirium duration was three days, with treatment refusal occurring in twenty-two patients and “duty of care” being used as an apparent beneficent related treatment framework in twelve patients.ConclusionsWhile impaired decision-making was indicated, the review was unable to indicate what patient characteristics flag the need for capacity assessment. Documentation relating to consent processes appeared deficient for this cohort. (shrink)

In this essay, I suggest that a slightly modified version of Freedman’s formulation of the clinical equipoise requirement is justified. I begin this essay with a brief discussion of the equipoise r...

I have argued elsewhere that the psychological criterion of personalidentity entails that a person is not an object, but a series ofpsychological events. As this is somewhat counter-intuitive,I consider whether the psychological theorist can argue that a person, while not a substance, exists in a way that is akin to theway that substances exist. I develop ten criteria that such a`quasi-substance' should meet, and I argue that a reasonablecase can be made to show that the psychological theorist's conception of a (...) person meets these criteria. (shrink)

François Jullien intervenes into the ontology debates to understand Chinese thought as an anti-ontology, but instead in terms of ‘life’, that is as a sort of vitalism. Chinese anti-ontology features the juxtaposition of the wu (there-is-not) with the you (there-is). This, I argue, maps onto theology’s counterposition of otherworldly and this-worldly. Here Daoism features an ascetic and unstratified wu in contraposition to Confucianism’s you of moderation and stratification. We contrast ontology’s causation with ‘efficacy’ in Jullien’s Chinese thought. We read Zhuangzi’s (...) ‘Equalization of Things’, where the inequalities of the you are equalized in the wu, as a sort of vitalist object energetics. We turn to Chinese ethics, and its driving virtue of yi. We understand the yi not as ‘righteousness’, which is a theological attribute of Christ, but instead as closer to political ‘right’, in China embedded in immanentist forms of life. Western Cartesian ontology is often contrasted with Chinese thought that works through a certain ‘analogism’. We read this, with Walter Benjamin’s Chinese ‘mimetic’ faculty, in terms of a vitalist energetics, a forcefield of the Ten Thousand Things. (shrink)

_An original interpretation of Merleau-Ponty on subjectivity, drawing from and challenging both the continental and analytic traditions._.

This paper situates the moral domain of practice within the context of a particular description of nursing practice – one that sees human interaction at the heart of that practice. Such a description fits not only with professional rhetoric but also with literature from patients and recent empirical work exploring the nature of nursing practice.Martha Levine in her 1977 description of ethics, within the context of nursing practice, indicated that what was important from an ethical perspective was how we interact (...) with each other, with patients and colleagues, on a daily basis. What enables such interaction to display moral sensitivity, insight into patient need, and a focus on the good for the patient? Of relevance when answering this question is the empirical evidence indicating that professional socialization, as a nurse or a doctor, may dull the individual’s moral sense. If this is the case, cognizance needs to be taken of such evidence when identifying theoretical approaches from mainstream ethics that may provide insight and value for nurse education. It is suggested that such insight and value can be gained from a consideration of the work of Aristotle, Murdoch, and Vetlesen. (shrink)

Classical pragmatism is committed to the thought that philosophy must be relevant to ordinary life. This commitment is frequently employed critically: to show that some idea is irrelevant to ordinary life is to prove it to be expendable. But the commitment is also constructive: pragmatists must strive to make their positive views relevant. Accordingly, one would expect the classical pragmatists to have fixed their attention on ethics, since this is the area of philosophy most attuned to everyday problems. Although ethics (...) was among Dewey’s persistent interests, Peirce wrote almost nothing on the subject, and James wrote very little. But what James did write exerts considerable influence on contemporary pragmatists, many of whom make frequent appeals to the dual components of James’s ethics, pluralism and meliorism. In this paper, we will pose three challenges to Jamesian ethics. As James’s ethics is unique, we begin with a sketch of his view. (shrink)

In the middle of the nineteenth century, advances in experimental psychology and the physiology of the sense organs inspired so-called "Back to Kant" Neo-Kantians to articulate robustly psychologistic visions of Kantian epistemology. But their accounts of the thing in itself were fraught with deep tension: they wanted to conceive of things in themselves as the causes of our sensations, while their own accounts of causal inference ruled that claim out. This paper diagnoses the source of that problem in views of (...) one Neo-Kantian, F. A. Lange, and argues that it is solved only by Ernst Mach. No less than Lange and other Neo-Kantians, Mach was inspired to develop a psychologistic account of the foundations of knowledge, but his account also includes a coherent denial of things in themselves' existence. Finally, this paper uses this account of Lange and Mach on things in themselves to illuminate Mach's relation to a certain strain of the Neo-Kantian philosophy of his own time: his views constitute a more fully coherent version of the psychologistic theory of knowledge Back to Kant figures tried to articulate. (shrink)

Most jurisdictions require that a mental capacity assessment be conducted using a functional model whose definition includes several abilities. In England and Wales and in increasing number of countries, the law requires a person be able to understand, to retain, to use or weigh relevant information and to communicate one’s decision. But interpreting and applying broad and vague criteria, such as the ability ‘to use or weigh’ to a diverse range of presentations is challenging. By examining actual court judgements of (...) capacity, we previously developed a descriptive typology of justifications used in the application of the Mental Capacity Act criteria. We here critically optimise this typology by showing how clear definitions—and thus boundaries—between the criteria can be achieved if the ‘understanding’ criterion is used narrowly and the multiple rationales that fall under the ability to ‘use or weigh’ are specifically enumerated in practice. Such a typology-aided practice, in theory, could make functional capacity assessments more transparent, accountable, reliable and valid. It may also help to create targeted supports for decision making by the vulnerable. We also discuss how the typology could evolve legally and scientifically, and how it lays the groundwork for clinical research on the abilities enumerated by the MCA. No data are available. This paper does not report any original data. (shrink)

Women and religion -- Reproductive futurism -- Political emancipation -- From the Cold War to the clash of civilizations -- Sexual emancipation.

Atrial natriuretic peptides appear to elicit their actions in some target tissues by binding to a novel cell‐surface transmembrane protein which possesses both peptide binding and guanylate cyclase activities. Ligand binding stimulates enzyme activity to produce increased intracellular concentrations of cyclic GMP which, in turn, mediates the cell's physiological response.

In my article, “Coming to Terms with the Antagonism Between Rhetorical Reflection and Political Agency,” I argue that academic desire is inherently frustrated by motives in tension with each other (2012). As rhetoric scholars, we are supposed to explore what we find politically interesting or important by isolating a chosen element of the political in order to perform a systematic study of that element and generate some insight about it. Yet graduate students quickly learn that moral fervor and political commitment (...) are not the same thing as studying something that they care about. And this moment of revelation is no less true for a partisan in the throws of a political campaign than it is for an academic shut away .. (shrink)

What follows is a discussion of three sets of experimental results that deal with various aspects of universal biological understanding among American and Maya children and adults. The first set of experiments shows that by the age of four-to-five years urban American and Yukatek Maya children employ a concept of innate species potential, or underlying essence, as an inferential framework for understanding the affiliation of an organism to a biological species, and for projecting known and unknown biological properties to organisms (...) in the face of uncertainty. The second set of experiments shows that the youngest Maya children do not have an anthropocentric understanding of the biological world. Children do not initially need to reason about non-human living kinds by analogy to human kinds. The third set of results show that the same taxonomic rank is cognitively preferred for biological induction in two diverse populations: people raised in the Mid-western USA and Itza' Maya of the Lowland Meso-american rainforest. This is the generic species  the level of oak and robin. These findings cannot be explained by domain-general models of similarity because such models cannot account for why both cultures prefer species-like groups in making inferences about the biological world, although Americans have relatively little actual knowledge or experience at this level. The implication from these experiments is that folk biology may well represent an evolutionary design: universal taxonomic structures, centred on essence-based generic species, are arguably routine products of our ‘habits of mind,' which may be in part naturally selected to grasp relevant and recurrent ‘habits of the world.' The science of biology is built upon these domain-specific cognitive universals: folk biology sets initial cognitive constraints on the development of any possible macro-biological theory, including the initial development of evolutionary theory. Nevertheless, the conditions of relevance under which science operates diverge from those pertinent to folk biology. For natural science, the motivating idea is to understand nature as it is ‘in itself,' independently of the human observer. From this standpoint, the species-concept, like taxonomy and teleology, may arguably be allowed to survive in science as a regulative principle that enables the mind to readily establish stable contact with the surrounding environment, rather than as an epistemic concept that guides the search for truth. (shrink)

Hermann Cohen (b. 1842, d. 1919), more than any other single figure, is responsible for founding the orthodox neo-Kantianism that dominated academic philosophy in Germany from the 1870s until the end of the First World War. Earlier German philosophers finding inspiration in Kant tended either towards speculative, metaphysical idealism, or sought to address philosophical questions with the resources of the empirical sciences, especially psychology. In contrast, Cohen’s seminal interpretation of Kant offered a vision of philosophy that decisively maintained its independence (...) from empirical psychology, without at the same time simply lapsing back into uncritical metaphysics. Cohen brought these attitudes to bear on a wide range of topics, writing systematically about epistemology, philosophy of science, ethics, law, political theory, and aesthetics. His anti-psychologism became a defining commitment not only of the Marburg School of neo-Kantianism, founded by Cohen himself, but of orthodox neo-Kantianism more generally. Indeed, that commitment ultimately defined the philosophical context from which, in the early twentieth century, both phenomenology and logical positivism emerged. No less significant than his influence on academic philosophy, Cohen was his generation’s preeminent German-Jewish public intellectual and religious philosopher. His philosophical ethics and political theory provided the foundation for a non-Marxist, Kantian democratic socialism that informed his more popular and topical writings. He argued publicly for universal suffrage and for the rights of workers to organize democratically-constituted collectives. He also saw deep points of connection between ethics and religion, and developed a view of Judaism as a fundamentally ethical system of belief and practice. He argued that monotheism was the historical source of the idea of universal ethical laws, and thus that Judaism offered the world its first model of a universalist morality. This view of Judaism’s ethical significance ultimately informed Cohen’s public defense of the Jews’ place in Germany not only against anti-Semitic attacks, but also against the arguments of early twentieth-century Zionists. However, Cohen’s influence on Jewish thought extends far beyond debates within Imperial Germany: his late religious writings inspired a broad renewal in twentieth-century Jewish ethics and philosophy of religion. (shrink)

Aristotle's treatment of trade in the Politics book one is usually regarded as especially hostile, and this is put down to snobbery and political prejudice on his part. The Greeks often regarded trade as a degrading thing for a free man to engage in, and it would be surprising if Aristotle's view of trade were entirely unconnected with this Greek sensibility. But there should be something more definite than a loose general affinity if a charge of prejudice is to be (...) taken seriously. A balance of hostile judgements over argued cases to back them up would be some sort of evidence for prejudice, and prima facie evidence against would be anything like a theory from which the hostile judgements followed as conclusions. Theories can be concocted to give the required conclusions, of course, and then we must try to decide how serious the theory is. It comes to this: is there so little in the reasons Aristotle gives for his condemnation of trade that they may be convincingly explained away and belittled as no more than expressions of attitudes? (shrink)