Protein‐carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate‐binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L‐, E‐ and P‐selectins, have domains homologous to other Ca2+‐dependent (C‐type) lectins. L‐selectin is expressed constitutively on lymphocytes, E‐selectin is expressed by activated endothelial cells, and P‐selectin is expressed by activated platelets and endothelial cells. Here, we review (...) the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L‐selectin on leukocyte surfaces. In contrast, E‐ and P‐selectins recognize specific carbohydrate determinants related to sialyl Lex antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitemient among glycoconjugate researchers that other carbohydrate‐binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions. (shrink)

Antimicrobial resistance is a major and increasing problem globally. Economics has engaged with this issue increasingly over the last 20 years. Much of this concerns assessments of the cost of various forms of resistance, but it also includes economic analyses of interventions and policies designed to contain resistance. Analysis has, however, thus far largely neglected possible distributional issues associated with such interventions and analysis. The article explores three normative bases for the conduct of economic analysis: welfarism; extra-welfarism focused on health (...) gain; and extra-welfarism focused on capability assessment. It then considers issues intrinsic to antimicrobial resistance in terms of the distributional implications and how these might be handled within economic analyses from each of the normative perspectives, before considering the actual focus of empirical studies on these distributional issues. The article concludes that the different normative starting points for economic analysis will affect how distributional issues are incorporated into analysis, but suggests that all analyses could benefit from greater discussion of these issues. (shrink)

The active inference framework offers an attractive starting point for understanding cultural cognition. Here, we argue that affective dynamics are essential to include when constructing this type of theory. We highlight ways in which interactions between emotional responses and the perception of those responses, both within and between individuals, can play central roles in both motivating and constraining sociocultural practices.

In this important survey, an international group of leading philosophers chart the development of philosophy of education in the twentieth century and point to signficant questions for its future. Presents a definitive introduction to the core areas of philosophy of education. Contains 20 newly-commissioned articles, all of which are written by internationally distinguished scholars. Each chapter reviews a problem, examines the current state of the discipline with respect to the topic, and discusses possible futures of the field. Provides a solid (...) foundation for further study. (shrink)

In this important survey, an international group of leading philosophers chart the development of philosophy of education in the twentieth century and point to signficant questions for its future. Presents a definitive introduction to the core areas of philosophy of education. Contains 20 newly-commissioned articles, all of which are written by internationally distinguished scholars. Each chapter reviews a problem, examines the current state of the discipline with respect to the topic, and discusses possible futures of the field. Provides a solid (...) foundation for further study. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

Socrates is one of the most important yet enigmatic philosophers of all time; his fame has endured for centuries despite the fact that he never actually wrote anything. In 399 B.C.E., he was tried on the charge of impiety by the citizens of Athens, convicted by a jury, and sentenced to death. About these facts there is no disagreement. However, as the sources collected in this book and the scholarly essays that follow them show, several of even the most basic (...) facts about these events were controversial in antiquity, and the questions persist today: How and why was Socrates brought to trial? Why did the jurors, members of the world's first democracy, find him guilty? When he was given an opportunity to escape execution, why did he refuse to do so and instead accept the punishment that he and his friends agreed was unjustly assigned to him? How exactly did Socrates die? Differences of opinion on these and other issues continue to arouse our curiosity and to challenge new generations of students and scholars. The Trial and Execution of Socrates: Sources and Controversies is the first work to collect in one place all of the major ancient sources on Socrates' death--those of both his critics and his defenders--as well as recent scholarly views. Part I includes new translations of Plato's Euthyphro, Apology, Crito, and the death scene from Phaedo, as well as other ancient sources that shed light on Socrates' trial and execution. Part II features some of the most influential recent scholarship on this historically momentous event with work by M. F. Burnyeat, Robert Parker, Mark L. McPherran, Thomas C. Brickhouse and Nicholas D. Smith, Richard Kraut, Christopher Gill, and Enid Bloch. Ideal for undergraduate surveys of ancient Greek philosophy and upper-level courses on Socrates and Socratic philosophy, this unique collection provides an unprecedented look into the many perplexing questions surrounding the trial and execution of this remarkable man. (shrink)

Cross-situational learning is a mechanism for learning the meaning of words across multiple exposures, despite exposure-by-exposure uncertainty as to the word's true meaning. We present experimental evidence showing that humans learn words effectively using cross-situational learning, even at high levels of referential uncertainty. Both overall success rates and the time taken to learn words are affected by the degree of referential uncertainty, with greater referential uncertainty leading to less reliable, slower learning. Words are also learned less successfully and more slowly (...) if they are presented interleaved with occurrences of other words, although this effect is relatively weak. We present additional analyses of participants’ trial-by-trial behavior showing that participants make use of various cross-situational learning strategies, depending on the difficulty of the word-learning task. When referential uncertainty is low, participants generally apply a rigorous eliminative approach to cross-situational learning. When referential uncertainty is high, or exposures to different words are interleaved, participants apply a frequentist approximation to this eliminative approach. We further suggest that these two ways of exploiting cross-situational information reside on a continuum of learning strategies, underpinned by a single simple associative learning mechanism. (shrink)

Sober (1992) has recently evaluated Brandon's (1982, 1990; see also 1985, 1988) use of Salmon's (1971) concept of screening-off in the philosophy of biology. He critiques three particular issues, each of which will be considered in this discussion.

Plato's Euthyrphro, Apology, andCrito portray Socrates' words and deeds during his trial for disbelieving in the Gods of Athens and corrupting the Athenian youth, and constitute a defense of the man Socrates and of his way of life, the philosophic life. The twelve essays in the volume, written by leading classical philosophers, investigate various aspects of these works of Plato, including the significance of Plato's characters, Socrates's revolutionary religious ideas, and the relationship between historical events and Plato's texts.

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine (...) data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

This volume brings together mostly previously unpublished studies by prominent historians, classicists, and philosophers on the roles and effects of religion in Socratic philosophy and on the trial of Socrates. Among the contributors are Thomas C. Brickhouse, Asli Gocer, Richard Kraut, Mark L. McPherran, Robert C. T. Parker, C. D. C. Reeve, Nicholas D. Smith, Gregory Vlastos, Stephen A. White, and Paul B. Woodruff.

Socrates is one of the most important yet enigmatic philosophers of all time; his fame has endured for centuries despite the fact that he never actually wrote anything. In 399 B.C.E., he was tried on the charge of impiety by the citizens of Athens, convicted by a jury, and sentenced to death (ordered to drink poison derived from hemlock). About these facts there is no disagreement. However, as the sources collected in this book and the scholarly essays that follow them (...) show, several of even the most basic facts about these events were controversial in antiquity, and the questions persist today: How and why was Socrates brought to trial? Why did the jurors, members of the world's first democracy, find him guilty? When he was given an opportunity to escape execution, why did he refuse to do so and instead accept the punishment that he and his friends agreed was unjustly assigned to him? How exactly did Socrates die? Differences of opinion on these and other issues continue to arouse our curiosity and to challenge new generations of students and scholars. The Trial and Execution of Socrates: Sources and Controversies is the first work to collect in one place all of the major ancient sources on Socrates' death--those of both his critics and his defenders--as well as recent scholarly views. Part I includes new translations of Plato's Euthyphro, Apology, Crito, and the death scene from Phaedo, as well as other ancient sources that shed light on Socrates' trial and execution. Part II features some of the most influential recent scholarship on this historically momentous event with work by M. F. Burnyeat, Robert Parker, Mark L. McPherran, Thomas C. Brickhouse and Nicholas D. Smith, Richard Kraut, Christopher Gill, and Enid Bloch (whose essay is published here for the first time). Ideal for undergraduate surveys of ancient Greek philosophy and upper-level courses on Socrates and Socratic philosophy, this unique collection provides an unprecedented look into the many perplexing questions surrounding the trial and execution of this remarkable man. (shrink)

In order to expound and defend the intentionalist thesis that human actions are intentionally determined by persons, selves, or agents themselves I first argue that teleological explanation, even though it is consistent with physicalism and scientifically respectable in the sense of being an attempt to establish the conditions under which things and events occur and to formulate laws that express such dependencies, is not exactly coordinate with and replaceable by mechanistic explanation. Then, I argue that living human beings must be (...) seen as teleological systems relative to the purposes and goals of intentional activities even though the human body may come as close as possible to being a mechanistic system relative to physical responses and electro-chemical-mechanical movements on the basis of certain insights drawn from Wittgenstein's works. Finally, I expound and defend a very strong version of the intentionalist thesis drawn from C. A. Campbell's 'Is “Freewill”; a Pseudo-Problem?' [5], and criticize an influential argument against this view which is due to C. D. Broad, 'Determinism, Indeterminism, and Libertarianism' [3]. (shrink)

Michael A. PetersBeijing Normal UniversityMy deepest condolences to Pepe, Dom and Marcus and to Jim’s grandchildren. Tina and I spent a lot of time at the Marshall family home, often attending dinn...

Adam Smith in Beijing is a huge and sprawling book, but Giovanni Arrighi has done a great service with his world-historical vision of today’s capitalism and the growing rivalry between a fading American empire and the rising power of China. This is a task beyond most of us, and one bound to put the writer at risk of criticism from many quarters. The book shines in two regards. One is to make geographical dynamics central to world-history ‐ which means (...) seeing the global economy as more than the sum of development-histories of many places or, worse, the spread of capitalism from one country to another. A second virtue is embedding economic history in the politics of the international state-system, featuring the use of force, imperial expansion, and the role of hegemonic powers. Nevertheless, Arrighi’s economic-geographic analysis fails to convince on a number of critical points, such as the origins of industrial revolution, why Europe overtook China in early modern times, why the US economy faltered after 1970, why finance has run amuck in our time, how Japan grew so enormously after World War II, or why China is expanding so prodigiously today. (shrink)

The theme of the 6th biennial Radical Philosophy Association Conference, held at Howard University in Washington, D.C. in November 2004, was "Philosophy Against Empire." The U.S. imperial project, pursued by both Republican and Democratic administrations, has many dimensions, including military force and the mechanisms for its legitimation; the global economy and flows of money and people across borders; and biopolitics, or the disciplining of bodies through the micro-mechanisms of power apart from traditional forms of sovereignty. These issues are explored in (...) depth in these collected and revised essays from the Conference, along with the forms of subjectivity that can resist and respond to the alienation produced within and by the imperial project, toward the creation of an alternative global order. Authors include Karsten Struhl, Ann Ferguson, Edmund Byrne, David Cormier, Harry Targ, Jo-Ann Pilardi, Lucinda Joy Peach, Devin Zane Shaw, Tzuchien Tho, Eduardo Mendieta, Richard Schmitt, Richard Jones, Richard Peterson, Peter Amato, William McBride, Omar Dahbour, Kory Schaff, David Schweickart, and Carol Gould. (shrink)

Ducklings were placed either singly or in pairs on a platform at two different heights. Both height and pairing influenced performance: More ducklings descended from the platform at low heights, and more single ducklings descended than paired ducklings. The social factor, pairing, made behavior more cautious and decreased the number of distress calls. A similar trend for pairing to influence performance was shown on the visual cliff. Without its peers, the duckling is a distressed animal. Previous careless behavior by ducklings (...) on the visual cliff may be ascribed to testing the ducklings outside their normal social environment. (shrink)

Orthodoxy maintains that Jean-Baptiste Say was a liberal political economist and the French disciple of Adam Smith. This article seeks to question such an interpretation through an examination of Say's early writings, and especially the first edition of his famous Traite d'economie politique (Paris, 1803). It is shown that Say was a passionate republican in the 1790s, but a republican of a particular kind. Through the influence of the radical Genevan exile Etienne Claviere, Say became convinced that only a (...) republican constitution would protect the gains of the Revolution. Furthermore, the foundation of a successful republic lay in the pursuit of specific virtuous manners, and in particular independence, equality, frugality and industriousness. Although in 1803 Say turned against supporters of republican constitutions he continued to demand the reformation of manners. His ultimate vision was a science of political economy which would foster republican manners, by instructing both legislators and the general populace. (shrink)

Despite wide acceptance that the attributes of living creatures have appeared through a cumulative evolutionary process guided chiefly by natural selection, many human activities have seemed analytically inaccessible through such an approach. Prominent evolutionary biologists, for example, have described morality as contrary to the direction of biological evolution, and moral philosophers rarely regard evolution as relevant to their discussions. -/- The Biology of Moral Systems adopts the position that moral questions arise out of conflicts of interest, and that moral systems (...) are ways of using confluences of interest at lower levels of social organiation to deal with conflicts of interest at higher levels. Moral systems are described as systems of indirect reciprocity: humans gain and lose socially and reproductively not only by direct transactions, but also by the reputations they gain from the everyday flow of social interactions. -/- The author develops a general theory of human interests, using senescence and effort theory from biology, to help analye the patterning of human lifetimes. He argues that the ultimate interests of humans are reproductive, and that the concept of morality has arisen within groups because of its contribution to unity in the context, ultimately, of success in intergroup competition. He contends that morality is not easily relatable to universals, and he carries this argument into a discussion of what he calls the greatest of all moral problems, the nuclear arms race. (shrink)

Since Freud, clinicians have understood that disturbing memories contribute to psychopathology and that new emotional experiences contribute to therapeutic change. Yet, controversy remains about what is truly essential to bring about psychotherapeutic change. Mounting evidence from empirical studies suggests that emotional arousal is a key ingredient in therapeutic change in many modalities. In addition, memory seems to play an important role but there is a lack of consensus on the role of understanding what happened in the past in bringing about (...) therapeutic change. The core idea of this paper is that therapeutic change in a variety of modalities, including behavioral therapy, cognitive-behavioral therapy, emotion-focused therapy, and psychodynamic psychotherapy, results from the updating of prior emotional memories through a process of reconsolidation that incorporates new emotional experiences. We present an integrated memory model with three interactive components – autobiographical (event) memories, semantic structures, and emotional responses – supported by emerging evidence from cognitive neuroscience on implicit and explicit emotion, implicit and explicit memory, emotion-memory interactions, memory reconsolidation, and the relationship between autobiographical and semantic memory. We propose that the essential ingredients of therapeutic change include: (1) reactivating old memories; (2) engaging in new emotional experiences that are incorporated into these reactivated memories via the process of reconsolidation; and (3) reinforcing the integrated memory structure by practicing a new way of behaving and experiencing the world in a variety of contexts. The implications of this new, neurobiologically grounded synthesis for research, clinical practice, and teaching are discussed. (shrink)

By a thorough study of the Posterior Analytics and related Aristotelian texts, Richard McKirahan reconstructs Aristotle's theory of episteme--science. The Posterior Analytics contains the first extensive treatment of the nature and structure of science in the history of philosophy, and McKirahan's aim is to interpret it sympathetically, following the lead of the text, rather than imposing contemporary frameworks on it. In addition to treating the theory as a whole, the author uses textual and philological as well as philosophical material (...) to interpret many important but difficult individual passages. A number of issues left obscure by the Aristotelian material are settled by reference to Euclid's geometrical practice in the Elements. To justify this use of Euclid, McKirahan makes a comparative analysis of fundamental features of Euclidian geometry with the corresponding elements of Aristotle's theory. Emerging from that discussion is a more precise and more complex picture of the relation between Aristotle's theory and Greek mathematics--a picture of mutual, rather than one-way, dependence. Originally published in 1992. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905. (shrink)