Directed cell migration is a fundamental component of numerous biological systems and is critical to the pathology of many diseases. Although the importance of secreted chemoattractant factors in providing navigational cues to migrating cells bearing specific chemoattractant receptors is now well‐established, how the function of these factors is regulated is not so well understood and may be of key importance to the design of new therapeutics for numerous human diseases. While regulation of migration clearly takes place on a number of (...) different levels, it is becoming clear that so‐called ‘atypical’ receptors play a role in scavenging, or altering the localisation of, chemoattractant molecules such as chemokines and complement components. These receptors do this through binding and/or internalising their chemoattractant ligands without activating signal transduction cascades leading to cell migration. The atypical chemokine receptor family currently comprises the receptors D6, DARC and CCX‐CKR. In this review, we discuss the evidence from in vitro and in vivo studies that these receptors play a role in regulating cell migration, and speculate that other orphan receptors may also belong to this family. Furthermore, with the advent of gene therapy on the horizon, the therapeutic potential of these receptors in human disease is also considered. BioEssays 29: 237–247, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro‐inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype most affected (...) through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro‐inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway. (shrink)

Computers are already approving financial transactions, controlling electrical supplies, and driving trains. Soon, service robots will be taking care of the elderly in their homes, and military robots will have their own targeting and firing protocols. Colin Allen and Wendell Wallach argue that as robots take on more and more responsibility, they must be programmed with moral decision-making abilities, for our own safety. Taking a fast paced tour through the latest thinking about philosophical ethics and artificial intelligence, the authors argue (...) that even if full moral agency for machines is a long way off, it is already necessary to start building a kind of functional morality, in which artificial moral agents have some basic ethical sensitivity. But the standard ethical theories don't seem adequate, and more socially engaged and engaging robots will be needed. As the authors show, the quest to build machines that are capable of telling right from wrong has begun. -/- Moral Machines is the first book to examine the challenge of building artificial moral agents, probing deeply into the nature of human decision making and ethics. (shrink)

The Rejected Body argues that feminist theorizing has been skewed toward non-disabled experience, and that the knowledge of people with disabilities must be integrated into feminist ethics, discussions of bodily life, and criticism of the cognitive and social authority of medicine. Among the topics it addresses are who should be identified as disabled; whether disability is biomedical, social or both; what causes disability and what could 'cure' it; and whether scientific efforts to eliminate disabling physical conditions are morally justified. Wendell (...) provides a remarkable look at how cultural attitudes towards the body contribute to the stigma of disability and to widespread unwillingness to accept and provide for the body's inevitable weakness. (shrink)

Quando nos detemos à querela recente sobre o enhancement, especialmente àquela que tem colocado em lados opostos bioconservadores e transhumanistas, não pode passar despercebido que pressuposições e mesmo concepções muito ingênuas sobre o homem se encontram no fundo do debate. No estudo que apresentaremos, buscaremos mostrar duas teses: antes de tudo, tentaremos evidenciar que tal querela formada em torno do enhancement é uma reformulação da querela que outrora envolveu a arte alquímica nos tempos medievais e renascentistas – arte cujo impulso (...) deu grande influxo ao ideal prático-transformador da ciência. Em segundo lugar, mostraremos que a atual controvérsia em torno do transhumanismo padece, em termos ontológicos, de problemas semelhantes àqueles que atormentavam o debate sobre aquela antiga arte. Por fim, deixaremos, entretanto, indicado que o esclarecimento das questões ontológicas envolvidas em tal controvérsia não eliminam necessariamente outras questões de ordem ética e política, as quais precisam certamente de um estudo complementar. (shrink)

The Holocaust demands a theological response. This essay considers that which has been presented by feminist theologians, of both Christian and Jewish faiths. In some cases, the response has been to further promote anti-Judaism in the fight against patriarchy, sustaining and perpetuating the portrayal of the Jew as Other, and even as Nazi. Conversely, other reactions have given rise to a fruitful Jewish-Christian dialogue which contests such a response, and replaces it with a constructive and healing interpretation of teaching and (...) events. A juxtaposition is presented between the anti-Judaic works of Christian feminist theologians such as Christa Mulack and Gerda Weiler, and the reaction and dialogue that have arisen between Jewish theologians, such as Susannah Heschel and Melissa Raphael, and their Christian counterparts, among whom are Rosemary Radford Ruether and Katherina von Kellenbach. (shrink)

Na seção 1.4.1 Do ceticismo quanto à razão do Tratado da Natureza Humana, David Hume apresenta o argumento cético, conhecido pelos intérpretes como o “argumento da diminuição”, que pode ser divido em duas partes: 1) dado o caráter falível de nossas operações cognitivas, todo o “conhecimento degenera em probabilidade”; e 2) dada a incerteza e a dúvida que comumente acompanham os nossos raciocínios probabilísticos, todo raciocínio é, no fim das contas, reduzido a nada e, consequentemente, somos levados à “extinção total (...) da crença e da evidência”. Apontaremos, em primeiro lugar, que o argumento cético contra a razão baseia-se no argumento cartesiano do “deus enganador” e, em segundo, que Hume rejeita que podemos endossar seriamente a “extinção total da crença e da evidência”. O que nos leva a propor a seguinte questão: em que consiste, para Hume, o status dos argumentos céticos? Responder tal pergunta implica em esclarecer outros dois problemas, pois, se não podemos atingir o “ceticismo total”, podemos, então, confiar em nossa faculdade de raciocínio? Se sim, sob quais condições podemos? Vê-se, afinal, que a solução de Hume consiste claramente em conferir limites à nossa faculdade de raciocínio, a fim de evitar sua autodestruição. (shrink)

This study aims to describe social network and social participation and to assess associations with depressive symptoms in older persons with increased risk for dementia in Germany. We conducted a cross-sectional observational study in primary care patients (aged 60-77) as part of a multicenter cluster-randomized controlled trial (AgeWell.de). We present descriptive and multivariate analyses for social networks (Lubben Social Network Scale and subscales) and social participation (item list of social activities) and analyze associations of these variables with depressive symptoms (Geriatric (...) Depression Scale). Of 1030 included patients, 17.2% were at risk for social isolation (Lubben Social Network Scale < 12). Looking at the subscales, a reduced non-family network was found almost twice as often as a reduced family network. Patients with depressive symptoms had significantly smaller social networks than patients without depression (p < 0.001). They rather engaged in social activities of low involvement level or no weekly social activity at all (p < 0.001). The study shows associations of depressive symptoms with a decreased social network and less social participation in elderly participants. Sufficient non-family contacts and weekly social activities seem to play an important role in mental health and should be encouraged in elderly primary care patients. (shrink)

Recently, there has been a resurgence of interest in general, comprehensive models of human cognition. Such models aim to explain higher-order cognitive faculties, such as deliberation and planning. Given a computational representation, the validity of these models can be tested in computer simulations such as software agents or embodied robots. The push to implement computational models of this kind has created the field of artificial general intelligence (AGI). Moral decision making is arguably one of the most challenging tasks for computational (...) approaches to higher-order cognition. The need for increasingly autonomous artificial agents to factor moral considerations into their choices and actions has given rise to another new field of inquiry variously known as Machine Morality, Machine Ethics, Roboethics, or Friendly AI. In this study, we discuss how LIDA, an AGI model of human cognition, can be adapted to model both affective and rational features of moral decision making. Using the LIDA model, we will demonstrate how moral decisions can be made in many domains using the same mechanisms that enable general decision making. Comprehensive models of human cognition typically aim for compatibility with recent research in the cognitive and neural sciences. Global workspace theory, proposed by the neuropsychologist Bernard Baars (1988), is a highly regarded model of human cognition that is currently being computationally instantiated in several software implementations. LIDA (Franklin, Baars, Ramamurthy, & Ventura, 2005) is one such computational implementation. LIDA is both a set of computational tools and an underlying model of human cognition, which provides mechanisms that are capable of explaining how an agent’s selection of its next action arises from bottom-up collection of sensory data and top-down processes for making sense of its current situation. We will describe how the LIDA model helps integrate emotions into the human decision-making process, and we will elucidate a process whereby an agent can work through an ethical problem to reach a solution that takes account of ethically relevant factors. (shrink)

Building artificial moral agents (AMAs) underscores the fragmentary character of presently available models of human ethical behavior. It is a distinctly different enterprise from either the attempt by moral philosophers to illuminate the “ought” of ethics or the research by cognitive scientists directed at revealing the mechanisms that influence moral psychology, and yet it draws on both. Philosophers and cognitive scientists have tended to stress the importance of particular cognitive mechanisms, e.g., reasoning, moral sentiments, heuristics, intuitions, or a moral grammar, (...) in the making of moral decisions. However, assembling a system from the bottom-up which is capable of accommodating moral considerations draws attention to the importance of a much wider array of mechanisms in honing moral intelligence. Moral machines need not emulate human cognitive faculties in order to function satisfactorily in responding to morally significant situations. But working through methods for building AMAs will have a profound effect in deepening an appreciation for the many mechanisms that contribute to a moral acumen, and the manner in which these mechanisms work together. Building AMAs highlights the need for a comprehensive model of how humans arrive at satisfactory moral judgments. (shrink)

We need a feminist theory of disability, both because 16 percent of women are disabled, and because the oppression of disabled people is closely linked to the cultural oppression of the body. Disability is not a biological given; like gender, it is socially constructed from biologically reality. Our culture idealizes the body and demands that we control it. Thus, although most people will be disabled at some time in their lives, the disabled are made "the other," who symbolize failure of (...) control and the threat of pain, limitation, dependency, and death. If disabled people and their knowledge were fully integrated into society, everyone's relation to her/his real body would be liberated. (shrink)

n his account of the state of exception, Agamben repeatedly relies upon what Hegel would have called emWesenslogik/em or #39;transcendental thinking#39;. Because of this reliance, the state of exception appears in Agamben#39;s account as the hidden ground of modern liberal democracies. When conceived as such a ground, it appears to be a condition of possibility that inexorably persists in the modern state. Moreover, within the state of exception all juridical order is suspended, leaving no normative or juridical criteria on the (...) basis of which to decide what the structure of any emergent political order should look like. This means that from the state of exception we can just as easily land in a totalitarian as we can in a liberal democratic or democratic socialist state. Without such criteria - lacking due to the total suspension characterizing the state of exception - Agamben#39;s own alignment with Benjaminian revolutionary messianism over Schmittian authoritarianism is arbitrary, and he leaves us with no basis for making any such decision ourselves. Drawing upon Hegel#39;s dialectic of freedom and his critique of transcendental thought, this paper argues that within the state of exception there is an implicit logic that points the way out of it. Furthermore, it does so in such a way that the state of exception is neither annexed by the structure of a predetermined juridical order along the lines proposed by Schmitt on the one hand nor posited it as a transcendental structure underlying or always preceding modern liberal democracies on the other. This alternative is overlooked by Agamben precisely because of his own insistence upon conceiving of the state of exception in a transcendent way. (shrink)

Chronic illness is a major cause of disability, especially in women. Therefore, any adequate feminist understanding of disability must encompass chronic illnesses. I argue that there are important differences between healthy disabled and unhealthy disabled people that are likely to affect such issues as treatment of impairment in disability and feminist politics, accommodation of disability in activism and employment, identification of persons as disabled, disability pride, and prevention and “cure” of disabilities.

ResumoO presente artigo visa mostrar o significado da filosofia biológica da técnica em Gilbert Simondon. Essa rubrica coloca em ação uma leitura da filosofia da técnica do filósofo francês como uma ontologia regional no interior de sua ontologia geral ontogenética, que, nesse regime específico, baseia-se em um modelo do orgânico. Para tanto, mostraremos que a individuação dos objetos técnicos, sua concretização marcada pela superdeterminação funcional, obriga-nos a pensá-los em sua organicidade e desde uma organologia geral. Ademais, os conceitos de adaptação (...) e de ambiente associado também contribuem enquanto aspectos biológicos que acompanham a concepção de Simondon do modo de existência dos seres técnicos. Como resultado, veremos que quanto mais concreto e adaptado - na série de sua evolução específica -, mais o objeto técnico se aproxima da individualidade propriamente biológica. Essa aproximação não terá, entretanto, o sentido de uma assimilação completa entre o técnico e o orgânico. Na autoprodução vital, permanece sempre um resto para além do maquínico, cuja demonstração é erigida por Simondon, por fim, com a ideia de uma origem vital absoluta dos objetos técnicos enquanto "mutação orientada". Apontaremos que tal origem não tem base meramente humana, mas se estende também para outras esferas do domínio vital.The present article aims to show the meaning of the biological philosophy of technique in Gilbert Simondon. This concept puts into action a reading of the French philosopher's philosophy of technique as a regional ontology within his ontogenetic general ontology, which in that particular scheme is based on an organic model. We will elaborate this to show that the individuation of technical objects, their concretization marked by their functional overdetermination, forces us to think of them in its organicity and from a general organology. Moreover, the concepts of adaptation and associated environment also contribute as biological aspects that accompany Simondon's conception of the mode of existence of technical beings. As a result, we will see that the more concrete and adapted the technical object is - in the series of its specific evolution - the more it comes closer to the proper biological individuality. This approximation will not have, however, the meaning of a complete assimilation between the technical and the organic. In the vital self-production, Simondon demonstrates that there always remains something beyond the machinical, namely, the idea of an absolute vital source of technical objects as a "guided mutation". We will show that such a source is not merely human, but also extends to other spheres of the vital domain. (shrink)

Interweaves Hegelian dialectic and the middle voice to develop a holistic account of life and nature, and the ethical orientation of human beings with respect to them.

In this paper I will argue that Hegel’s account of the category of life in the Science of Logic provides ontological grounds for the recognition of living species along with their various ecosystems as the proper objects of ethical regard for environmental ethics. I will begin by enumerating some of the salient problems that have arisen in the more well known theoretical attempts to articulate human duties to nonhuman beings. Then after a brief discussion of Hegel’s methodology and the justification (...) for turning to his ontological account, I will explicate Hegel’s ontology of life with a view toward these problems and issues, presenting my argument as to why that account is relevant to environmental ethics and deriving from it a normative framework that implies a duty to preserve species, habitats, and biological diversity. Finally, I will suggest how the Hegelian account presented here might circumvent the shortcomings of the previously discussed theories while accommodating some of their concerns and provide solutions for some of the problems to which they call attention. (shrink)

In this essay I will attempt to show that Derrida not only mistakenly reads the Hegelian text in terms of reflection, but that his own way of thinking could be characterized from a Hegelian perspective as itself reflective. For this I will not focus upon those writings of Derrida which are explicitly “about” Hegel, nor will I compare those places in both the Derridian and Hegelian corpora which seem to present a contiguity in an at least superficial resemblance between concepts, (...) such as Hegelian difference vis-à-vis Derridian différance. Rather, I will focus upon one of Derrida’s texts which indicates his own contributions to the field of thinking and writing and the directions for inquiry initiated in his work, as well as his engagement with Hegel. Such a text is his masterful essay, White Mythology: Metaphor in the Text of Philosophy, a writing overtly concerned with the difficulties posed by metaphoricity in the text of philosophy and the attempt in the latter to domesticate and “interiorize” its tropic reserve or condition of possibility within the concept of metaphor itself, which turns out to be a philosopheme. The problems of philosophy are posed in terms of such mastery and interiorization. Since my concern in this essay is to problematize this kind of reading by showing that it presupposes reflective distinctions, I will not here attempt a positive philosophical account of metaphoricity per se. Indeed, Derrida will indicate what he takes to be the conditions of the impossibility of such an account, but it is precisely his reasons for this impossibility that I find problematic in terms of reflection. (shrink)

In The Ticklish Subject, Žižek argues that the Hegelian concrete universal is not the organic comprehensive totality that it is often assumed to be. Rather, he argues that Hegel's concrete universality is defined in its very concretion by an irreducible rupture, gap, or trauma that not only neither closes it off from otherness nor assimilates otherness within the same, but forever opens it to otherness, constituting it as such exposure. However, by understanding the function of negativity in Hegel's argument in (...) a foundational way, Žižek posits as final what is merely a transitional stage. As a result, he not only misconstrues concrete universality and substitutes for it a particularized universal which, as such, remains abstract, but in doing so he passes by the implications in his own account that could lead to a positive conception of concrete universality above and beyond the strictly negative and empty formality he takes it to be. By avoiding Žižek's foundationalist way of framing the category of universality we can thereby articulate a logic of implications in it that leads us out of the still abstract shape, to which Žižek limits it, to its truly concrete form. Furthermore, the latter contains political implications that are lost in Žižek's version. (shrink)

The essays in Part I of _Beyond Poststructuralism seek_ to demonstrate fallacies of structuralist and poststructuralist thought that remain potent even though the theoretical structures that led to their enunciation have lost much of their original influence. These fallacies include the idea that one must avoid the consideration of authorial intention; that meanings are undecidable; that there is no justification for seeking unity in a text; that all hierarchies of value are reversible; that history is no more than an open (...) contest among competing narrative constructions; and that the very nature of language makes the falsifiability of statements about human experience impossible. The essays in Part II suggest ways to bring literary study into closer relation with human experience of the world. Their authors emphasize the role of literature in providing new perspectives and broadening the range of available alternatives to what is threatening, unjust, fallacious, or absurd in social and cultural structures. Contributors are Bernard Bergonzi, John Holloway, Wendell V. Harris, A. D. Nuttall, Raymond Tallis, John Searle, Richard Levin, Robert Scholes, James Battersby, David Bromwich, Quentin Kraft, Michael Fischer, Charles Altieri, Christopher Clausen, Gayle Greene, André Lefevere, Daniel R. Schwarz, Virgil Nemoianu, and Martha Nussbaum. (shrink)

For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory‐developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory‐formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures. How many of the new categories of products require new forms of regulatory (...) oversight, or at least extensive forms of testing, remains unclear.Any effort to improve the governance of synthetic biology should start with a rich understanding of the different possible science‐policy interfaces that could help to inform governance. CBA falls into a subset of the overall range of possibilities, and which interface is appropriate may turn out to depend on context, on the demands of the decision at hand. In what follows, we lay out a typology of interfaces. After that, we turn to the question of how to draw upon the range of possible interfaces and effectively address the factual and moral complexities of emerging technologies. We propose a governance model built around structures that we call “governance coordinating committees.” GCCs are intended to be mechanisms for accommodating the complexities of innovations that have far‐ranging societal impacts. The production of biofuels, for example, could contaminate water supplies and have a destructive environmental impact if not managed correctly. The introduction of a gene drive could have economic and environmental impacts that are not restricted to one nation. Forging appropriate means for determining and evaluating those societal impacts, to the best of a corporation's, industry's, or government's ability, is central to responsible research and innovation. Public policy must be shaped in a manner that accommodates as many concerns as possible and minimizes risks. (shrink)