The affinities of antibodies (Abs) for their target antigens (Ags) gradually increase in vivo following an infection or vaccination, but reach saturation at values well below those realisable in vitro. This ‘affinity ceiling’ could in many cases restrict our ability to fight infections and compromise vaccines. What determines the affinity ceiling has been an unresolved question for decades. Here, we argue that it arises from the strength of the chain of protein complexes that is pulled by B cells during the (...) process of Ag acquisition. The affinity ceiling is determined by the strength of the weakest link in the chain. We identify the weakest link and show that the resulting affinity ceiling can explain the Ab affinities realized in vivo, providing a conceptual understanding of Ab affinity maturation. We explore plausible evolutionary underpinnings of the affinity ceiling, examine supporting evidence and alternative hypotheses and discuss implications for vaccination strategies. (shrink)

; tibi M. Bibulus quaerenti se de caelo seruasse respondit idemque in contione dixit, ab Appio tuo fratre productus, te omnino, quod contra auspicia adoptatus esses, tribunum non fuisse. tua denique omnis actio posterioribus mensibus fuit, omnia quae C. Caesar egisset, quod contra auspicia essent acta, per senatum rescindi oportere; quod si fieret, dicebas te tuis umeris me custodem urbis in urbem relaturum.’.

Temporal Logic: From Ancient Ideas to Artificial Intelligence deals with the history of temporal logic as well as the crucial systematic questions within the field. The book studies the rich contributions from ancient and medieval philosophy up to the downfall of temporal logic in the Renaissance. The modern rediscovery of the subject, which is especially due to the work of A. N. Prior, is described, leading into a thorough discussion of the use of temporal logic in computer science and the (...) understanding of natural language. Temporal Logic: From Ancient Ideas to Artificial Intelligence thus interweaves linguistic, philosophical and computational aspects into an informative and inspiring whole. (shrink)

The present study seeks to lay out the most basic elements of the ontology of classical Aš‘arite theology. In several cases this requires a careful examination of the traditional and the formal lexicography of certain key expressions. The topics primarily treated are: how they understood “Being/ existence” and “being/existent” and essential natures; the systematic exploitation of the equivocities of certain expressions within a general context in which other than words there are no universals proves to be elegant as well as (...) insightful; the basic categories of primary entities: independant beings and nonindependant beings, created and uncreated, the equivocity of “being/existent” as predicated of contingent entities on the one hand and of God and His attributes on the other, and certain problems that arise because of the rigid application of the system's underlying analytic principles. Nous essayons ici de presenter les éléments fondamentaux de l'ontologie de l'aš‘arisme classique. Pour quelques expressions, il a fallu examiner la lexicographie et ordinaire et technique pour bien comprendre leur emploi et leur signification. Les sujets examinés sont: le sens de “Etre/existence” et de “être/existant” et le concept de réalité essentielle; l'emploi nuancé des équivocités de quelques expressions dans un contexte où les seuls universaux sont des mots, emploi qui se révèle philosophiquement élégant; les catégories fondamentales des êtres: êtres indépendants et êtres non-indépendants, soit créés soit incréés, l'équivocité de “être/existant” dit des êtres contingents d'une part, de Dieu et ses attributs d'autre part, et enfin quelques difficultiés qui résultent de l'application rigide des principes analytiques du système. (shrink)

The wish to extend the human lifespan has a long tradition in many cultures. Optimistic views of the possibility of achieving this goal through the latest developments in medicine feature increasingly in serious scientific and philosophical discussion. The authors of this paper argue that research with the explicit aim of extending the human lifespan is both undesirable and morally unacceptable. They present three serious objections, relating to justice, the community and the meaning of life.

This book provides a clear and nuanced appraisal of Hegel's treatment of Africa, India, and Islam, and of the implications of this treatment for postcolonial and global studies. Analyzing Hegel's master-slave dialectic and his views on Africa, India, and Islam, it situates these views not only within Hegel's historical scheme but also within a broader European philosophical context and the debates they have provoked within Hegel scholarship. Each chapter explores various in depth readings of Hegel by postcolonial critics, investigating both (...) the Eurocentric and potentially global nature of his dialectic. Ultimately, the book shows both where of this profoundly influential thinker archetypally embodies certain Eurocentric traits that have characterized modernity and how, ironically, he himself gives us the tools for working towards a more global vision. Offering a concise introduction not only to an important dimension of Hegel's thought - his orientation towards "empire" - but also to the various issues raised by postcolonial theory and global studies, this book will be of use to philosophers as well as advanced students of literary and cultural theory alike. (shrink)

Some of the commentators on Intricate Ethics complain of my method. One finds the main ideas ‘Kammouflaged’ because the relevant causal distinctions are so fine-grained and the cases that illustrate them so numerous. Some say that they do not have the intuitions about many cases that I have, that I concoct dubious and ad hoc distinctions and invest them with moral significance; I am Ptolemaic in that new crystalline spheres and epicycles are constantly being added in an attempt to fix (...) the appearances. (shrink)

This paper investigates four questions related to ethical issues associated with the involvement of engineers and scientists in 'military work', including the influence of ethical values and beliefs, the role of gendered perspectives and moves beyond the purely technical. It fits strongly into a human (and planet)-centred systems perspective and extends my previous AI and Society papers on othering and narrative ethics, and ethics and social responsibility. It has two main contributions. The first involves an analysis of the literature through (...) the application of different ethical theories and the application of gendered analysis to discussion of masculinities in engineering and the military. The second is a survey of scientists and engineers to investigate their opinions and experiences. The conclusions draw together the results of these two contributions to provide preliminary responses to the four questions and include a series of recommendations covering education and training, ethical approval of work not involving human participants or animals, the need for organisational support, approaches covering wider perspectives and the encouragement of individual ethical commitment. (shrink)

Objective: To assess the opinions and practice patterns of obstetrician-gynaecologists on acceptance and use of free drug samples and other incentive items from pharmaceutical representatives.Methods: A questionnaire was mailed in March 2003 to 397 members of the American College of Obstetricians and Gynecologists who participate in the Collaborative Ambulatory Research Network.Results: The response rate was 55%. Most respondents thought it proper to accept drug samples , an informational lunch , an anatomical model or a well-paid consultantship from pharmaceutical representatives. A (...) third of the respondents thought that their own decision to prescribe a drug would probably be influenced by accepting drug samples. Respondents were more likely to think the average doctor’s prescribing would be influenced by acceptance of the items than theirs would be . Respondents who distributed drug samples to patients indicated doing so because of patients’ financial need and for their convenience and less so as a result of knowledge of the efficacy of the sample product . A third of respondents agreed that interactions with industry should be more strictly regulated.Conclusion: Obstetrician-gynaecologists largely indicated that they would act in accordance with what they think is proper regarding accepting incentive items from pharmaceutical representatives. Although accepting free drug samples was considered to be appropriate more often than any other item, samples were most commonly judged to be influential on prescribing practices. The widely accepted practice of receiving and distributing free drug samples needs to be examined more carefully. (shrink)

In 2005 St Andrews Studies published a volume of essays by Anscombe entitled Human Life, Action and Ethics, followed in 2008 by a second with the title Faith in a Hard Ground. Both books were highly praised. This third volume brings essays on the thought of historical philosophers in which Anscombe engages directly with their ideas and arguments. Many are published here for the first time and the collection provides further testimony to Anscombe's insight and intellectual imagination.

"M. F. Simone Roberts's A Poetics of Being-Two is animated by a lively and engaging voice, drawing readers in with a sense of serious purpose working (delightfully) in tandem with a sense of humor. Roberts's aesthetics and her close readings of Yves Bonnefoy, St-John Perse, and Jorie Graham clearly demonstrate the literary effectiveness of Irigarayan sexual difference as an analytic trope, even as they emphasize the philosophical and political possibilities sexual difference opens up for feminism, environmentalism, and all levels of (...) contemporary cultural critique and activism."—Gail M. Schwab, Hofstra University -/- In An Ethics of Sexual Difference, Irigaray calls for a new poetics in the sense of both art and life. Rather than a critique from within philosophy, A Poetics of Being-Two tests Irigaray's ethics by extending it to other sites of cultural production. Where Irigaray's method finds stirrings and repressions of sexual difference in philosophy, this project explores that tension in poetics. Building from Irigaray's ethics, the book describes a poetics of being-two as concerns gendered subjectivity in literary poetics and then traces the on-going emergence of a poetics of being-two in the post-symbolist poetic tradition. Irigaray scholars will be interested in the sustained interpolation of Irigaray's ethical concepts as principles for a critical aesthetics and in their hermeneutic application in reading a literary tradition. Readers in comparative literature will find the first sustained feminist engagements with the major French poets Bonnefoy and Perse and an elucidation of their influence on the Pulitzer Prize winning poet Jorie Graham. (shrink)

Scholars offer several options for Matthew’s value of the leper’s story in his narrative that range from revealing Jesus’ attributes of compassion and sympathy, manifesting God’s empire, to portraying Jesus’ function as a temple. Although these suggestions aptly portray Matthew’s rhetorical use of the leper’s healing in his narrative to address societal concerns of his time, for lack of referring to the social setting of the narrative, they do not capture the holistic healthcare system embodied by Jesus in Matthew’s narrative (...) that portrays Jesus as a superior healer to the rest of the other healers in the Roman Empire. The findings of the research for this article establish the argument that employing ethnomedical anthropology as a lens to read the leper’s healing narrative in Matthew 8:1–4 in the context of Matthew’s social setting reveals Matthew’s ideology for a transcendent and immanent Christology. The aim of the article is to demonstrate the effectiveness of medical anthropological theory in explaining the dynamics of health and healing reflected in biblical texts.Contributions: This article contributes to the interdisciplinary approach to the study of religion by employing a ethnomedical anthropological perspective to read the leper’s healing in Matthew 8.1–4 in reference to the first century CE health systems in the Roman Empire. This approach procured that Matthew’s immanent and transcendent perspectives of Christology is crucial in demonstrating the text’s function in constructing and sustaining the identity of Matthew’s community in antiquity. (shrink)

Problem: The inclusion of the observer into scientific observation entails a vicious circle of having to observe the observer as dependent on observation. Second-order science has to clarify how its underlying circularity can be scientifically conceived. Method: Essayistic and conceptual analysis, sporadically illustrated with agent-based experiments. Results: Second-order science - implying science in general - is fundamentally and ineluctably circular. Implications - The circularity of second-order science asks for analytical methods able to cope with phenomena of complex causation and “synchronous (...) asynchrony,” such as tools for analyzing non-linearly interacting dynamics, decentralized, clustered networks and in general, systems of complex interacting components. Key Words: Observer dependency, second-order science, complexity, information, intentionality. (shrink)

(2000). Ecological rationality and its contents. Thinking & Reasoning: Vol. 6, No. 4, pp. 375-384.

This book examines the ideology of elite lawyers and judges from the Gilded Age through the New Deal. Between 1866 and 1937, a coherent outlook shaped the way the American bar understood the sources of law, the role of the courts, and the relationship between law and the larger society. William M. Wiecek explores this outlook--often called "legal orthodoxy" or "classical legal thought"--which assumed that law was apolitical, determinate, objective, and neutral. American classical legal thought was forged in the heat (...) of the social crises that punctuated the late nineteenth century. Fearing labor unions, immigrants, and working people generally, American elites, including those on the bench and bar, sought ways to repress disorder and prevent political majorities from using democratic processes to redistribute wealth and power. Classical legal thought provided a rationale that assured the legitimacy of the extant distribution of society's resources. It enabled the legal suppression of unions and the subordination of workers to management's authority. As the twentieth-century U.S. economy grew in complexity, the antiregulatory, individualistic bias of classical legal thought became more and more distanced from reality. Brittle and dogmatic, legal ideology lost legitimacy in the eyes of both laypeople and ever-larger segments of the bar. It was at last abandoned in the "constitutional revolution of 1937", but--as Wiecek argues in this detailed analysis--nothing has arisen since to replace it as an explanation of what law is and why courts have such broad power in a democratic society. (shrink)

Malthus did not leave us with a systematic treatment of colonization, but from remarks scattered throughout his publications and correspondence it is possible to assemble a fairly coherent account of his views on the advantages and disadvantages of colonies, and on the reasons why some have failed and others succeeded. Included in these scattered remarks are some comparisons between his own views on colonies and those of Adam Smith. The question of the relationship between Malthus and Adam Smith is a (...) rather complex and subtle one, and cannot be given the full consideration it deserves in one short paper. But, as a general summary, it can be said that Malthus had a high regard for Smith and considered himself a follower and disciple of Smith, by contrast with Ricardo, James Mill, and McCulloch etc., whom he considered as exponents of a ‘New System of Political Economy”. His own Principles of Political Economy was conceived as a collection of ‘tracts or essays”, not as a new systematic treatise replacing the Wealth of Nations, Joseph Gamier in his article ‘Malthus” in the Dictionnaire de l'Economie Politique, 1852, saw that the title of the Principles was in fact a misnomer: ‘Malgré son titre, le livre sur les Principes n'est point un traité complet, mais seulement une collection de dissertations.” In what was probably intended as a criticism of Ricardo's Principles of Political Economy and Taxation, 1817, Malthus stated that the ‘present period … seems to be unpropitious to the publication of a new systematic treatise on political economy”, and, referring to Smith's work, stated that ‘the treatise which we already possess is still of the very highest value”. Nevertheless, despite professing his affiliation, Malthus did not hesitate to criticize Smith when he disagreed with him. He recognized that the Wealth of Nations contained ‘controverted points” and that it would require some ‘additions … which the more advanced stage of the science has rendered necessary”. (shrink)

The purpose of this article should become plain during the reading of it, but perhaps some prior explanation is needed. Almost from the beginning of my study of the paṭiccasamuppāda I have had the notion that it could not have come into existence in the form the usual twelvefold formulation takes. For reasons which I try to make clear this twelvefold formulation is not a satisfactory statement of what it is supposed to explain, namely the reasons for each individual's continued (...) rebirths. I feel - and sadly I have to emphasize, before someone else does it for me, that in the final analysis I am relying more or less on intuition for my attitude towards the twelvefold formulation - that if one person alone had been responsible for the usually referred to formulation, and especially if that one person had been the Buddha, then those anomalies that now prevail would never have existed. (shrink)

There is a long-standing claim within feminist literature that women speak with a 'different voice' (Gilligan 1982), that it is both possible and desirable to have an ethics from the standpoint of women (Noddings 1990), that the standpoint of women is a better starting point for adequate knowledge of the world (Harding 1993). This claim is central to ecofeminist politics, that women have a particular perspective on the relationship between humanity and nature and have a moral/political calling to reweave the (...) world (Diamond and Orenstein 1990) or heal the wounds of an ecologically destructive social order (Plant 1989). In this essay I will not be making the claim that women per se have a superior vision or a higher moral authority, but that an ethics that does not take account of the gendered nature of society is doomed to failure as it will confront neither the material structure of human society or the way in which that structure impacts on the materiality of the relationship between humanity and nature. (shrink)

The first comprehensive introduction to cover the entire span of Kierkegaard’s authorship. Explores how the two strands of his writing—religious discourses and pseudonymous literary creations—influenced each other Accompanies the reader chronologically through all the philosopher’s major works, and integrates his writing into his biography Employs a unique “how to” approach to help the reader discover individual texts on their own and to help them closely examine Kierkegaard’s language Presents the literary strategies employed in Kierkegaard’s work to give the reader insight (...) into subtext. (shrink)

This book studies the interfaces of ethics, economics, and politics. Public policy issues involve all three of these subjects. Although it may be seen as suggesting the nucleus of a joint university course, the book is accessible to and should interest all those concerned with political decisions. Any such decision needs a criterion for judging whether one action or outcome is better than another. Even a dictator must to some extent be concerned about the economic welfare of the citizens; and (...) a democratic government more so. But how is a person's economic welfare to be judged? Furthermore, any political decision affects the economic welfare of different people differently. How then is the welfare of a community to be judged? This is an ethical question. Underlying any coherent public policy there must be a relevant moral code. (shrink)

Falsafat wa-ḥayāt Abī Hāshim al-Jubbāʼī wa-madrasatuh -- al-Tawallud ʻinda al-Muʻtazilah.