In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro systems have revealed important (...) regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands such (...) as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

This review explores the hypothesis that regulation of nucleocytoplasmic shuttling is a means of driving differentiation, using spermatogenesis as a model. The transition from undifferentiated spermatogonial stem cell to terminally differentiated spermatozoon is, at its most basic, a change in the repertoire of expressed genes. To effect this, the complement of nuclear proteins, such as transcription factors and chromatin remodelling components must change. Current knowledge of the nuclear proteins and nucleocytoplasmic transport machinery relevant to spermatogenesis is consolidated in this review, (...) and their functional linkages are highlighted not only as a means of regulating nuclear protein composition, but also as a key mechanism regulating gene transcription and hence cell fate. Through this, we hypothesize that male germ cell differentiation is mediated through regulation of nuclear transport machinery components, and thereby of the access of critical factors to the nucleus. The importance of nucleocytoplasmic trafficking to male germ cell differentiation is discussed, using the sex-determining factors Sry and SOX9, cell cycle regulators, CREM and cofactors and the Smads as specific examples, together with the roles in gametogenesis for particular nuclear transport factors in Caenorhabditis elegans and Drosophila. BioEssays 27:1011–1025, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Interaction of ligands such as epidermal growth factor and interferon‐γ with the extracellular domains of their plasma membrane receptors results in internalization followed by translocation into the nucleus of the ligand and/or receptor. There has been reluctance, however, to ascribe signaling importance to this, the focus instead being on second messenger pathways, including mobilization of kinases and inducible transcription factors (TFs). The latter, however, fails to explain the fact that so many ligands stimulate the same second messenger cascades/TFs, and yet (...) show distinct gene activation profiles. This is particularly apt in the case of the seven STAT TFs that are held to be the mediators of the distinct cellular functions of over 60 ligands. The current review focuses on five representative nuclear localizing ligands for which there is documentation of translocation into the cytosol and nucleus through well‐characterized pathways, in addition to a role in gene activation by ligand/receptor in the nucleus. BioEssays 26:993‐1004, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

We investigate maximal free sequences in the Boolean algebra \ {/}\text {fin}\), as defined by Monk :593–610, 2011). We provide some information on the general structure of these objects and we are particularly interested in the minimal cardinality of a free sequence, a cardinal characteristic of the continuum denoted \. Answering a question of Monk, we demonstrate the consistency of \. In fact, this consistency is demonstrated in the model of Shelah for \ :433–443, 1992). Our paper provides a streamlined (...) and mostly self contained presentation of this construction. (shrink)

Philosophy flourished in Australia after the war. There was spectacular growth in both the number of departments and the number of philosophers. On top of this philosophy spread beyond the philosophy departments. Serious studies, and interest in philosophy is now common in faculties as diverse as law, science and education. Neither is this development merely quantitative, the Australian researcher has come of age and contributes widely to international debates. At least one movement originated in Australia. This makes the study of (...) philosophy in Australia timely, evidenced by the number of articles concerned with this area that begin to appear in international journals. In Australia itself there is growing interest in the history of the country's philosophical development. There are discussions in conferences and meetings: the matter is now the subject of courses. (shrink)

This book takes a major step in the philosophy of education by moving back past the Enlightenment and reinstating Aristotelian Virtue at the heart of moral education.

This handbook presents a comprehensive introduction to the core areas of philosophy of education combined with an up-to-date selection of the central themes. It includes 95 newly commissioned articles that focus on and advance key arguments; each essay incorporates essential background material serving to clarify the history and logic of the relevant topic, examining the status quo of the discipline with respect to the topic, and discussing the possible futures of the field. The book provides a state-of-the-art overview of philosophy (...) of education, covering a range of topics: Voices from the present and the past deals with 36 major figures that philosophers of education rely on; Schools of thought addresses 14 stances including Eastern, Indigenous, and African philosophies of education as well as religiously inspired philosophies of education such as Jewish and Islamic; Revisiting enduring educational debates scrutinizes 25 issues heavily debated in the past and the present, for example care and justice, democracy, and the curriculum; New areas and developments addresses 17 emerging issues that have garnered considerable attention like neuroscience, videogames, and radicalization. The collection is relevant for lecturers teaching undergraduate and graduate courses in philosophy of education as well as for colleagues in teacher training. Moreover, it helps junior researchers in philosophy of education to situate the problems they are addressing within the wider field of philosophy of education and offers a valuable update for experienced scholars dealing with issues in the sub-discipline. Combined with different conceptions of the purpose of philosophy, it discusses various aspects, using diverse perspectives to do so. Contributing Editors: Section 1: Voices from the Present and the Past: Nuraan Davids Section 2: Schools of Thought: Christiane Thompson and Joris Vlieghe Section 3: Revisiting Enduring Debates: Ann Chinnery, Naomi Hodgson, and Viktor Johansson Section 4: New Areas and Developments: Kai Horsthemke, Dirk Willem Postma, and Claudia Ruitenberg. (shrink)

Over 40 years of research have shown that traumatic brain injury affects brain volume. However, technical and practical limitations made it difficult to detect brain volume abnormalities in patients suffering from chronic effects of mild or moderate traumatic brain injury. This situation improved in 2006 with the FDA clearance of NeuroQuant®, a commercially available, computer-automated software program for measuring MRI brain volume in human subjects. More recent strides were made with the introduction of NeuroGage®, commercially available software that is based (...) on NeuroQuant® and extends its utility in several ways. Studies using these and similar methods have found that most patients with chronic mild or moderate traumatic brain injury have brain volume abnormalities, and several of these studies found—surprisingly—more abnormal enlargement than atrophy. More generally, 102 peer-reviewed studies have supported the reliability and validity of NeuroQuant® and NeuroGage®. Furthermore, this updated version of a previous review addresses whether NeuroQuant® and NeuroGage® meet the Daubert standard for admissibility in court. It concludes that NeuroQuant® and NeuroGage® meet the Daubert standard based on their reliability, validity, and objectivity. Due to the improvements in technology over the years, these brain volumetric techniques are practical and readily available for clinical or forensic use, and thus they are important tools for detecting signs of brain injury. (shrink)

Previous research has found that populist attitudes and conspiracy mentality – here summarised as anti-establishment attitudes – increase when people feel threatened. Two types of intergroup threat have been distinguished, namely realistic threats (pertaining to socio-economic resources, climate, or health), and symbolic threats (pertaining to cultural values). However, there is no agreement on which types of threat and corresponding appraisals would be most important in predicting anti-establishment attitudes. We hypothesise that it is the threat itself, irrespective of its cause, that (...) predicts anti-establishment attitudes. In the current paper, we conducted new (multilevel) regression analyses on previously collected data from four high-powered studies with multiple time points (Study 1) or collected in multiple nations (Studies 2–4). All studies included a populist attitudes scale, a conspiracy mentality scale, and different types of threat and emotion measures, reflecting both realistic and symbolic threats. Across studies, both realistic and symbolic threats positively predicted anti-establishment attitudes. The results support an emotional appraisal approach to anti-establishment attitudes, which highlights the importance of anxiety and feeling threatened regardless of what type of event elicits the threat. (shrink)

Plato’s Lysis shows Socrates in conversation with two boys he has met at a wrestling school, Lysis and Menexenus. Their debate revolves around the notion of philia, seeking to pin down the nature of this relation, who or what takes part in it, and what causes it. The word philiahas usually been translated as “friendship” but has a wider application in this dialogue, as it encompasses a variety of friendly and loving attitudes toward both people and things. The kinds of (...) interpersonal philia evoked include erotic attachments, kinship relations, utility-based relations, and playful companionship. Roughly two-thirds into the dialogue, the focus turns to a more general theory of desiderative attachments and the question of their ultimate telos and cause. The conversation ends, at least on the face of it, in an impasse, an aporia, when the interlocutors find themselves thrown back to the point from where they started, and no attempt to answer the question of what philia is or what motivates it has stuck. The Lysis nevertheless offers many incentives for further discussion and has elicited radically different responses from its interpreters as to what its real message is. For instance, does it promote a form of utilitarian egoism according to which human attachment can never, or should never, be altruistically motivated? Or does it hint at a very different concept of interpersonal love based on the idea that friendship, as it were, completes us since it connects us with those that share the same values? Does this dialogue stay within the familiar ambit of Socratic ethics, centered around the question of what it takes to achieve happiness (eudaimonia) in a human life, without a concern for metaphysical questions? Or, quite the contrary, does its discussion of the highest object of love (to proton philon) point forward to the metaphysical program of Plato’s so-called middle-period dialogues and especially to the notions of the form of the good or the form of the beautiful, notions which are at the center of the Republic and the Symposium? These questions and others will continue to be debated about this puzzling dialogue. The essays assembled in the present volume address many of these topics. (shrink)

Time is often said to play in quantum mechanics an essentially different role from position: whereas position is represented by a Hermitian operator, time is represented by a c-number. This discrepancy has been found puzzling and has given rise to a vast literature and many efforts at a solution. In this paper it is argued that the discrepancy is only apparent and that there is nothing in the formalism of quantum mechanics that forces us to treat position and time differently. (...) The apparent problem is caused by the dominant role point particles play in physics and can be traced back to classical mechanics. (shrink)

Time is often said to play in quantum mechanics an essentially different role from position: whereas position is represented by a Hermitian operator, time is represented by a c-number. This discrepancy has been found puzzling and has given rise to a vast literature and many efforts at a solution. In this paper it is argued that the discrepancy is only apparent and that there is nothing in the formalism of quantum mechanics that forces us to treat position and time differently. (...) The apparent problem is caused by the dominant role point particles play in physics and can be traced back to classical mechanics. (shrink)

We investigate maximal free sequences in the Boolean algebra \ {/}\text {fin}\), as defined by Monk :593–610, 2011). We provide some information on the general structure of these objects and we are particularly interested in the minimal cardinality of a free sequence, a cardinal characteristic of the continuum denoted \. Answering a question of Monk, we demonstrate the consistency of \. In fact, this consistency is demonstrated in the model of Shelah for \ :433–443, 1992). Our paper provides a streamlined (...) and mostly self contained presentation of this construction. (shrink)

We investigate maximal free sequences in the Boolean algebra \ {/}\text {fin}\), as defined by Monk :593–610, 2011). We provide some information on the general structure of these objects and we are particularly interested in the minimal cardinality of a free sequence, a cardinal characteristic of the continuum denoted \. Answering a question of Monk, we demonstrate the consistency of \. In fact, this consistency is demonstrated in the model of Shelah for \ :433–443, 1992). Our paper provides a streamlined (...) and mostly self contained presentation of this construction. (shrink)

BackgroundA patient who fulfils the due diligence requirements for euthanasia, and is medically suitable, is able to donate his organs after euthanasia in Belgium, the Netherlands and Canada. Since 2012, more than 70 patients have undergone this combined procedure in the Netherlands. Even though all patients who undergo euthanasia are suffering hopelessly and unbearably, some of these patients are nevertheless willing to help others in need of an organ. Organ donation after euthanasia is a so-called donation after circulatory death (DCD), (...) Maastricht category III procedure, which takes place following cardiac arrest, comparable to donation after withdrawal of life sustaining therapy in critically ill patients. To minimize the period of organ ischemia, the patient is transported to the operating room immediately after the legally mandated no-touch period of 5 min following circulatory arrest. This means that the organ donation procedure following euthanasia must take place in the hospital, which appears to be insurmountable to many patients who are willing to donate, since they already spent a lot of time in the hospital. Case presentationThis article describes the procedure of organ donation after euthanasia starting at home (ODAEH) following anesthesia in a former health care professional suffering from multiple system atrophy. This case is unique for at least two reasons. He spent his last conscious hours surrounded by his family at home, after which he underwent general anaesthesia and was intubated, before being transported to the hospital for euthanasia and organ donation. In addition, the patient explicitly requested the euthanasia to be performed in the preparation room, next to the operating room, in order to limit the period of organ ischemia due to transport time from the intensive care unit to the operating room. The medical, legal and ethical considerations related to this illustrative case are subsequently discussed.ConclusionsOrgan donation after euthanasia is a pure act of altruism. This combined procedure can also be performed after the patient has been anesthetized at home and during transportation to the hospital. (shrink)

This article presents a generalization of the Condorcet Jury Theorem. All results to date assume a fixed value for the competence of jurors, or alternatively, a fixed probability distribution over the possible competences of jurors. In this article, we develop the idea that we can learn the competence of the jurors by the jury vote. We assume a uniform prior probability assignment over the competence parameter, and we adapt this assignment in the light of the jury vote. We then compute (...) the posterior probability, conditional on the jury vote, of the hypothesis voted over. We thereby retain the central results of Condorcet, but we also show that the posterior probability depends on the size of the jury as well as on the absolute margin of the majority. (shrink)

Paraorthomodular posets are bounded partially ordered sets with an antitone involution induced by quantum structures arising from the logico-algebraic approach to quantum mechanics. The aim of the present work is starting a systematic inquiry into paraorthomodular posets theory both from algebraic and order-theoretic perspectives. On the one hand, we show that paraorthomodular posets are amenable of an algebraic treatment by means of a smooth representation in terms of bounded directoids with antitone involution. On the other, we investigate their order-theoretical features (...) in terms of forbidden configurations. Moreover, sufficient and necessary conditions characterizing bounded posets with an antitone involution whose Dedekind–MacNeille completion is paraorthomodular are provided. (shrink)

Introduction Introduction / Jan de Vries 1 Art in History / Gary Schwartz 7 History in Art / J. W. Smit 17 Pt. I Art and Reality Market Scenes As Viewed by an Art Historian / Linda Stone-Ferrier 29 Market Scenes As Viewed by a Plant Biologist / Willem A. Brandenburg 59 Marine Paintings and the History of Shipbuilding / Richard W. Unger 75 Skies and Reality in Dutch Landscape / John Walsh 95 Some Notes on Interpretation / E. de (...) Jongh 119 Are These Girls Really So Neat? On Kitchen Scenes and Method / Jochen Becker 139 Didactic and Disguised Meanings? Several Seventeenth-Century Texts on Painting and the Iconological Approach to Northern Dutch Paintings of This Period / Eric J. Sluijter 175 The Changing Face of Realism / Lyckle de Vries 209 Pt. II Art, Economy, and Society Art History / Jan de Vries 249 The Volume and Value of Paintings in Holland at the Time of the Dutch Republic / Ad van der Woude 285 Works of Art in Seventeenth-Century Amsterdam: An Analysis of Subjects and Attributions / John Michael Montias 331 Conclusion Science, Commerce, and Art: Neglected Topics at the Junction of History and Art History / David Freedberg 377 Biographical Notes on the Authors 429 Index. (shrink)

In this paper we show that several classes of partially ordered structures having paraorthomodular reducts, or whose sections may be regarded as paraorthomodular posets, admit a quite natural notion of implication, that admits a suitable notion of adjointness. Within this framework, we propose a smooth generalization of celebrated Greechie’s theorems on amalgams of finite Boolean algebras to the realm of Kleene lattices.

Was heißt es, einen literarischen Text zu interpretieren? Wie können Interpretationen begründet werden? Können wir mit Interpretationen Anspruch auf Erkenntnis erheben? Können Interpretationen wahr sein? In welcher Weise fließt das Wissen von Interpreten in ihre Interpretationen ein? Aus der Perspektive verschiedener Disziplinen suchen die Beiträge dieses Bandes Antworten auf diese und andere fundamentale Fragen, die sich mit der Interpretation von Literatur verbinden. Der einleitende Beitrag gibt einen Überblick über wichtige Themen und Probleme, die gegenwärtig im Hinblick auf die Theorie und (...) Praxis der Literaturinterpretation diskutiert werden. Die in den folgenden vier Sektionen versammelten Studien widmen sich unter anderem Fragen nach dem Interpretationsbegriff, der Geltung und der methodisch geleiteten Begründung von Interpretationen, den kognitiven Operationen beim Verstehen und Interpretieren von Literatur sowie den Problemen, die sich in der Praxis der Literaturinterpretation angesichts der spezifischen Beschaffenheit literarischer Texte ergeben. Vertreten sind die Fachgebiete der deutschsprachigen Literaturwissenschaft, Philosophie, Linguistik, Mediävistik, Anglistik und Computerphilologie. [What does it mean to interpret a work of literature? How can interpretations be justified? Can interpretations serve as a source of knowledge? Is it possible for interpretations to be true? How does the knowledge of interpreters contribute to their interpretations? The essays comprised in this volume look for answers to these and other fundamental questions regarding the interpretation of literature. The introduction provides an overview of the main issues and problems in contemporary debates on the theory and practice of interpretation. The articles are grouped into four sections and cover topics like the concept of interpretation, the validity of interpretations, the methods for justifying interpretations, the cognitive processes that are involved in understanding and interpreting literature, and address problems that arise in the practice of interpretation and in light of the specific characteristics of literary texts. The contributors to this volume come from a variety of disciplines such as literary studies, philosophy, linguistics, and the digital humanities.]. (shrink)

The Cleitophon has recently been discovered to be Plato's dialogue introducingThe Republic. In this volume of essays, Editor, Translator, and Author Mark Kremer introduces seminal work that understands The Cleitophon as an ancient discussion of what scholars today refer to as posthumanism and postmodernism. Thoroughly original, this volume is an invaluable resource to all disciplines that attempt to come to terms with our emerging global society.

We argue that abduction does not work in isolation from other inference mechanisms and illustrate this through an inference scheme designed to evaluate multiple hypotheses. We use game theory to relate the abductive system to actions that produce new information. To enable evaluation of the implications of this approach we have implemented the procedures used to calculate the impact of new information in a computer model. Experiments with this model display a number of features of collective belief-revision leading to consensus-formation, (...) such as the influence of bias and prejudice. The scheme of inferential calculations invokes a Peircian concept of ‘belief’ as the propensity to choose a particular course of action. (shrink)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from (...) social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic. (shrink)

Collected and edited by Noah Levin -/- Table of Contents: -/- UNIT ONE: INTRODUCTION TO CONTEMPORARY ETHICS: TECHNOLOGY, AFFIRMATIVE ACTION, AND IMMIGRATION 1 The “Trolley Problem” and Self-Driving Cars: Your Car’s Moral Settings (Noah Levin) 2 What is Ethics and What Makes Something a Problem for Morality? (David Svolba) 3 Letter from the Birmingham City Jail (Martin Luther King, Jr) 4 A Defense of Affirmative Action (Noah Levin) 5 The Moral Issues of Immigration (B.M. Wooldridge) 6 The Ethics of (...) our Digital Selves (Noah Levin) -/- UNIT TWO: TORTURE, DEATH, AND THE “GREATER GOOD” 7 The Ethics of Torture (Martine Berenpas) 8 What Moral Obligations do we have (or not have) to Impoverished Peoples? (B.M. Wooldridge) 9 Euthanasia, or Mercy Killing (Nathan Nobis) 10 An Argument Against Capital Punishment (Noah Levin) 11 Common Arguments about Abortion (Nathan Nobis & Kristina Grob) 12 Better (Philosophical) Arguments about Abortion (Nathan Nobis & Kristina Grob) -/- UNIT THREE: PERSONS, AUTONOMY, THE ENVIRONMENT, AND RIGHTS 13 Animal Rights (Eduardo Salazar) 14 John Rawls and the “Veil of Ignorance” (Ben Davies) 15 Environmental Ethics: Climate Change (Jonathan Spelman) 16 Rape, Date Rape, and the “Affirmative Consent” Law in California (Noah Levin) 17 The Ethics of Pornography: Deliberating on a Modern Harm (Eduardo Salazar) 18 The Social Contract (Thomas Hobbes) -/- UNIT FOUR: HAPPINESS 19 Is Pleasure all that Matters? Thoughts on the “Experience Machine” (Prabhpal Singh) 20 Utilitarianism (J.S. Mill) 21 Utilitarianism: Pros and Cons (B.M. Wooldridge) 22 Existentialism, Genetic Engineering, and the Meaning of Life: The Fifths (Noah Levin) 23 The Solitude of the Self (Elizabeth Cady Stanton) 24 Game Theory, the Nash Equilibrium, and the Prisoner’s Dilemma (Douglas E. Hill) -/- UNIT FIVE: RELIGION, LAW, AND ABSOLUTE MORALITY 25 The Myth of Gyges and The Crito (Plato) 26 God, Morality, and Religion (Kristin Seemuth Whaley) 27 The Categorical Imperative (Immanuel Kant) 28 The Virtues (Aristotle) 29 Beyond Good and Evil (Friedrich Nietzsche) 30 Other Moral Theories: Subjectivism, Relativism, Emotivism, Intuitionism, etc. (Jan F. Jacko). (shrink)