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)

Theologie und Metaphysik stehen in einem Spannungsverhältnis. Versuchen der Rehabilitierung eines starken metaphysischen Systemsdenkens steht das 'nachmetaphysische Denken' entgegen, welches das Projekt einer rationalen Metaphysik verabschiedet. Wendel und Breul unternehmen einen Vermittlungsversuch: Sie formulieren eine 'Metaphysik nach Kant' als Leitparadigma der Theologie, die ernst nimmt, dass Metaphysik für eine rationale Begründung des Glaubens unverzichtbar ist, sie zugleich jedoch methodisch nur in der Verwurzelung in einer Praxis personaler Lebensformen haltbar ist. So gelingt es diesem Neuansatz, eine an die Moderne anschlussfähige (...) praktische Begründung religiöser Hoffnung zu entwickeln."-- Back cover. (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)

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)

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)

Wendell T. Bush presents a detailed analysis of Avenarius's philosophy, focusing on the standpoint of pure experience. This work from the 1900s offers a deep dive into philosophical concepts and their implications. Bush's meticulous research and interpretation provide a comprehensive understanding of Avenarius's contributions to philosophy. The book stands as a testament to the profound impact of philosophical thought on human understanding.

The development of autonomous, robotic weaponry is progressing rapidly. Many observers agree that banning the initiation of lethal activity by autonomous weapons is a worthy goal. Some disagree with this goal, on the grounds that robots may equal and exceed the ethical conduct of human soldiers on the battlefield. Those who seek arms-control agreements limiting the use of military robots face practical difficulties. One such difficulty concerns defining the notion of an autonomous action by a robot. Another challenge concerns how (...) to verify and monitor the capabilities of rapidly changing technologies. In this article we describe concepts from our previous work about autonomy and ethics for robots and apply them to military robots and robot arms control. We conclude with a proposal for a first step toward limiting the deployment of autonomous weapons capable of initiating lethal force. (shrink)

The challenge of designing computer systems and robots with the ability to make moral judgments is stepping out of science fiction and moving into the laboratory. Engineers and scholars, anticipating practical necessities, are writing articles, participating in conference workshops, and initiating a few experiments directed at substantiating rudimentary moral reasoning in hardware and software. The subject has been designated by several names, including machine ethics, machine morality, artificial morality, or computational morality. Most references to the challenge elucidate one facet or (...) another of what is a very rich topic. This paper will offer a brief overview of the many dimensions of this new field of inquiry. (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)

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)

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)

BackgroundThe biopharmaceutical industry operates at the intersection of life sciences, clinical research, clinical care, public health, and business, which presents distinct operational and ethical challenges. This setting merits focused bioethics consideration to complement legal compliance and business ethics efforts. However, bioethics as applied to a biopharmaceutical industry setting often is construed either too broadly or too narrowly with little examination of its proper scope.Main textAny institution with a scientific or healthcare mission should engage bioethics norms to navigate ethical issues that (...) arise from the conduct of biomedical research, delivery of clinical care, or implementation of public health programs. It is reasonable to assume that while bioethics norms must remain constant, their application will vary depending on the characteristics of a given setting. Context “specification” substantively refines ethics norms for a particular discipline or setting and is an expected, needed and progressive ethical activity. In order for this activity to be meaningful, the scope for bioethics application and the relevant contextual factors of the setting need to be delineated and appreciated. This paper defines biopharmaceutical bioethics as: the application of bioethics norms (concepts, principles, and rules) to the research, development, supply, commercialization, and clinical use of biopharmaceutical healthcare products. It provides commentary on this definition, and presents five contextual factors that need to be considered when applying bioethics norms to a biopharmaceutical industry setting: (1) dual missions; (2) timely and pragmatic guidance; (3) resource stewardship; (4) multiple stakeholders; and (5) operational complexity.ConclusionUnderstanding the scope of the biopharmaceutical enterprise and contextual factors of a biopharmaceutical industry setting is foundational for the application of bioethics norms. Establishing a common language and approach for biopharmaceutical bioethics will facilitate breadth and depth of discussion and subsequent implementation to benefit patients, the healthcare system and society. (shrink)

A despeito de ser bem menos conhecido atualmente, o problema do ceticismo quanto à razão foi um assunto bastante relevante entre os autores dos séculos XVII e XVIII, da mesma maneira que o ceticismo quanto ao mundo exterior. Nesse sentido, busco apresentar os impactos de Huet sobre a posição de Hume no que concerne ao ceticismo quanto à razão do Tratado da Natureza Humana, particularmente a partir da versão pirrônica elaborada por Huet do argumento cartesiano do “Deus enganador”. Assim, como (...) mostrarei neste trabalho, Hume está correto pelo menos ao associar o argumento cético quanto à razão ao ceticismo pirrônico. Palavras-chaves: Huet. Hume. Ceticismo. Pirronismo. Razão. (shrink)

Displays of eye movements may convey information about cognitive processes but require interpretation. We investigated whether participants were able to interpret displays of their own or others' eye movements. In Experiments 1 and 2, participants observed an image under three different viewing instructions. Then they were shown static or dynamic gaze displays and had to judge whether it was their own or someone else's eye movements and what instruction was reflected. Participants were capable of recognizing the instruction reflected in their (...) own and someone else's gaze display. Instruction recognition was better for dynamic displays, and only this condition yielded above chance performance in recognizing the display as one's own or another person's. Experiment 3 revealed that order information in the gaze displays facilitated instruction recognition when transitions between fixated regions distinguish one viewing instruction from another. Implications of these findings are discussed. (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)

RESUMO Neste artigo, argumento que o compromisso de Hume com objetos independentes da mente está baseado em dois tipos de realismo ou sistema de realidades: (a) um realismo ingênuo baseado em uma crença vulgar injustificada que identifica percepções e objetos, e (b) um realismo representacional ou sistema filosófico de dupla existência. Em primeiro lugar, enfatizo que a questão filosófica “Se existem ou não corpos” não pode ser considerada um caso completo de ceticismo não mitigado, porque Hume aceita um ceticismo mitigado (...) compatível com o realismo vulgar e representacional. Além disso, argumento que, enquanto a crença vulgar nos corpos está baseada em um assentimento injustificado, a teoria da dupla-existência está baseada tanto em um assentimento injustificado quanto em um assentimento racionalmente justificado (que corrige o primeiro). Considerando todos esses pontos, concluo que o ceticismo mitigado de Hume permite e exige uma crença ou suposição de existências contínuas e distintas, e que isso deve, na prática, assumir formas vulgares e filosóficas em diferentes momentos. (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)

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)