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)

Regulation of the cytoplasmic stability of mRNAs has recetly been identified as a major control mechanism which governs mRNA levels in a variety of eukaryotic systems. In this review we discuss what is known about several experimental systems that exhibit regulated mRNA stability, describe the mechanisms that cells may use to achieve control of mRNA degradation, and suggest areas of future investigation likely to provide new insights into this process.

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)

This review of Medium, Messenger, Transmission outlines and introduces the media philosophy of Sybille Krämer. Her argument that communication initiates a relationship with the other as an ethical act is read alongside the work of Emmanuel Levinas, before exploring the impact of our contemporary obligation to be available for communication in working environments that seem not to encourage or instantiate this moral encounter.

Iphigenia Aulidensis was produced after the poet's death, probably in 405 BC. The aim of this paper is to recover the text of this production, which I call FP for First Performance. Probably Euripides left behind an incomplete draft, which was finished by Euripides Minor, the poet's son or nephew. The text we have contains, as Page showed in 1934, material added for a fourth-century revival and other still later interpolations. Diggle's edition tries to separate original Euripides from all later (...) hands on the basis of style. But if we want to recover the amalgam that was FP we need to be attentive to the plot that is implied by the most clearly genuine portions: we can't confine ourselves to what appears to be Euripidean since more than one hand contributed to FP. A discovery about the plot gives us some objective basis for reconstructing FP. Our transmitted text contains two different conceptions of Calchas' prophecy, only one of which belonged to FP. Several passages scattered throughout the play imply that it was public, made to the entire army, but other passages say that it was private, restricted to Agamemnon's inner circle, with the army left in the dark. The secret prophecy motif, I argue, is the work of a fourth century producer, whom I call the Reviser. Its purpose was to introduce into the play scenes where Greek soldiers, ignorant of the real reason for Iphigenia's coming to Aulis, might make naive comments or ask questions that are highly ironic in view of the actual situation, this being an emotional effect he found congenial. We find two such passages in places that are under grave suspicion: the entrance of Clytaemestra, where there is a chorus of Argives who felicitate Iphigenia on her wonderful prospects, and the first messenger, who reports naive questions from the soldiery. Both these passages have linguistic and dramaturgical features that make it virtually certain that neither Euripides nor Euripides Minor wrote them. Working from these we can detect the Reviser's hand at other places in the play and reconstruct its original lineaments. One satisfying result is that the business of baby Orestes, played by a doll, can be shown to be the work of the Reviser. The play ended with Iphigenia's departure for the altar, and there was no substitution of a stag. Like Menoeceus, Macaria and their kin, Iphigenia pays for the victory of her country with her blood, and there is no happy ending. (shrink)

Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP‐GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG‐GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) (...) or RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second messengers in a protein‐kinase‐independent fashion. These proteins are exchange factors for Ras family GTPases that operate in pathways that run parallel to the classic kinase‐dependent pathways. The rapidly emerging recognition of the functions of these “non‐kinase” effectors in diverse processes such as insulin secretion, thymocyte development, asthma and malignant transformation creates new opportunities for discovery and identifies potential new therapeutic targets. BioEssays 26:730–738, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Odysseus has just entered the acting area following the choral song, during which he witnessed the Cyclops butchering, cooking and then eating two of his companions. In these lines Odysseus seemingly presents himself as being at a loss for words, and claims that what he witnessed inside the cave is not to be believed. These are, of course, nothing more than rhetorical ploys, with frequent parallels in Euripides and elsewhere. When Odysseus says οὐ πιστά he means not that what he (...) is about to recount lacks credibility—he does, after all, expect the satyrs to accept his account as reliable—but that it surpasses the bounds of ordinary human experience. And the account that follows belies his apparent profession of being at a loss for words, since he is about to deliver what is in effect a messenger-speech of over fifty lines. Expressions of aphasia are common in Euripides, sometimes accompanied, as here, by lengthy exposition. Characters use such expressions to indicate that the circumstances in which they find themselves are beyond the power of language to convey. There is, therefore, something discordant in Odysseus immediately following his expression of aphasia by saying that what he has witnessed is ‘like stories’, especially when he is about to tell the story of the circumstances in which he finds himself. It is the purpose of this note to suggest that the words μύθοις εἰκότ’ have been universally misunderstood, and that Odysseus is here saying something quite other than that the events in the cave have a greater resemblance to stories than to reality. (shrink)

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding studies, second messenger (...) assays, ion imaging, patch‐clamp electrophysiology and gene silencing can readily be applied. Drosophila is also ideal for the study of new control strategies for insect pests since the receptors and ion channels that many new animal health drugs and crop protection chemicals target can be expressed in this cell line. In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. BioEssays 24:1066–1073, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

In this volume, Stephen M. Gardiner and David A. Weisbach present arguments for and against the relevance of ethics to global climate policy. Gardiner argues that climate change is fundamentally an ethical issue, since it is an early instance of a distinctive challenge to ethical action, and ethical concerns are at the heart of many of the decisions that need to be made. Consequently, climate policy that ignores ethics is at risk of.

Galileo’s telescopic lunar observations, announced in Siderius Nuncius (1610), were a triumph of observational skill and ingenuity. Yet, unlike the Medicean stars, Galileo’s lunar “discoveries” were not especially novel. Indeed, Plutarch had noted the moon’s uneven surface in classical times, and many other renaissance observers had also turned their gaze moonward, even (in Harriot’s case) aided by telescopes of their own. Moreover, what Galileo and his contemporaries saw was colored by the assumptions they already had. Copernicans assumed the moon was (...) a terrestrial satellite, thus Galileo saw its mountains and Kepler “saw” the dwellings of its inhabitants. Aristotelians assumed the moon was a perfect sphere, so they saw differences in density and rarity in the lunar body. Theory corrected the results of observation, so Galileo’s lunar observations, like those that had come before, proved nothing. Yet this failure contained the germ of Galileo’s success, since the Siderius Nuncius gave observation a rhetorical force it did not have before. Observers on all sides set out to see for themselves what Galileo reported. Hence, all parties now had to answer to what they saw, whatever they believed. Thus, the Siderius Nuncius ultimately changed the grounds upon which natural philosophical argument and debate was carried out. In this new empirical arena, the Galilean science would eventually prevail. (shrink)

Legal theorists are familiar with John Finnis's book Natural Law and Natural Rights, but usually overlook his interventions in US constitutional debates and his membership of a group of conservative Catholic thinkers, the 'new natural lawyers', led by theologian Germain Grisez. In fact, Finnis has repeatedly advocated conservative positions concerning lesbian and gay rights, contraception and abortion, and his substantive moral theory derives from Grisez. Bamforth and Richards provide a detailed explanation of the work of the new natural lawyers within (...) and outside the Catholic Church - the first truly comprehensive explanation available to legal theorists - and criticize Grisez's and Finnis's arguments concerning sexuality and gender. New natural law is, they argue, a theology rather than a secular theory, and one which is unappealing in a modern constitutional democracy. This book will be of interest to legal and political theorists, ethicists, theologians and scholars of religious history. (shrink)

We articulate a holistic understanding of hope, going beyond the common conceptualization of hope in terms of positive affect and cognition by considering what hope means for the underprivileged. In the recognition that hope is always situated in a particular place, we explore the perspective of the privileged and the underprivileged, clarifying how spatial contexts shape their goals for the future and their agency toward attaining these goals. Where some people experience precarity due to their disability, race, gender, sexuality, and (...) social class, others enjoy enhanced agency due to their privilege. In our analysis, this loss of agency does not mean the underprivileged are hopeless; instead, it suggests that hope can incorporate negative affect and cognition. In our view, a spatial understanding acknowledges the power of hope in discouraging situations, and it points to practical measures through which hope can be cultivated by marginalized communities. (shrink)

After two generations of emphasis on governmental inefficiency and the need for deregulation, we now see growing interest in the possibility of constructive governance, alongside public calls for new, smarter regulation. Yet there is a real danger that regulatory reforms will be rooted in outdated ideas. As the financial crisis has shown, neither traditional market failure models nor public choice theory, by themselves, sufficiently inform or explain our current regulatory challenges. Regulatory studies, long neglected in an atmosphere focused on deregulatory (...) work, is in critical need of new models and theories that can guide effective policy-making. This interdisciplinary volume points the way toward the modernization of regulatory theory. Its essays by leading scholars move past predominant approaches, integrating the latest research about the interplay between human behavior, societal needs and regulatory institutions. The book concludes by setting out a potential research agenda for the social sciences. (shrink)

Employee mobility is a phenomenon that challenges workplace ethics. This paper argues that despite on‐going attempts by management and consultants to build and install employee loyalty, and despite the complexity of relationships between employees and their organization, employee mobility remains a common phenomenon in today’s market. Courts, at least Israeli courts, perceive the employee–employer relationship as almost purely contractual and thus strive to protect workers first, often ignoring deeper commitments such as loyalty. This results in a certain dissonance in the (...) relationships between employees and employers. (shrink)

Consciousness as used here, refers to the private, subjective experience of being aware of our perceptions, thoughts, feelings, actions, memories including the intimate experience of a unified self with the capacity to generate and control actions and psychological contents. This compelling, intuitive consciousness-centric account has, and continues to shape folk and scientific accounts of psychology and human behavior. Over the last 30 years, research from the cognitive neurosciences has challenged this intuitive social construct account when providing a neurocognitive architecture for (...) a human psychology. Growing evidence suggests that the executive functions typically attributed to the experience of consciousness are carried out competently, backstage and outside subjective awareness by a myriad of fast, efficient non-conscious brain systems. While it remains unclear how and where the experience of consciousness is generated in the brain, we suggested that the traditional intuitive explanation that consciousness is causally efficacious is wrong-headed when providing a cognitive neuroscientific account of human psychology. Notwithstanding the compelling 1st-person experience that convinces us that subjective awareness is the mental curator of our actions and thoughts, we argue that the best framework for building a scientific account is to be consistent with the biophysical causal dependency of prior neural processes. From a 3rd person perspective,, we propose that subjective awareness lacking causal influence, is than our experience of being aware, our awareness of our psychological content, knowing that we are aware, and the belief that that such experiences are evidence of an agentive capacity shared by others. While the human mind can be described as comprising both conscious and nonconscious aspects, both ultimately depend on neural process in the brain. In arguing for the counter-intuitive epiphenomenal perspective, we suggest that a scientific approach considers all mental aspects of mind including consciousness in terms of their underlying, preceding biological changes, in the realization that most brain processes are not accompanied by any discernible change in subjective awareness. (shrink)

Employee mobility is a phenomenon that challenges workplace ethics. This paper argues that despite on‐going attempts by management and consultants to build and install employee loyalty, and despite the complexity of relationships between employees and their organization, employee mobility remains a common phenomenon in today’s market. Courts, at least Israeli courts, perceive the employee–employer relationship as almost purely contractual and thus strive to protect workers first, often ignoring deeper commitments such as loyalty. This results in a certain dissonance in the (...) relationships between employees and employers. (shrink)

David Lewis' objection to a generic theory of modality which he calls ‘magical ersatzism’ is that its linchpin, a relation he calls ‘selection’, must be either an internal or an external relation, and that this is unintelligible either way. But the problem he points out with classifying selection as internal is really just an instance of the general problem of how we manage to grasp underdetermined predicates, is not peculiar to magical ersatzism, and is amenable to some familiar solutions. (...) He provides no compelling grounds for thinking that classifying selection as external is unintelligible, and his argument has a false presupposition. I conclude that magical ersatzism is still a viable option in the metaphysics of modality. (shrink)

The assumptions that literary criticism and philosophy are closely linked—and that both disciplines can learn much from each other—lead David White to examine key passages in James Joyce’s novels both as a philosopher and as literary critic. In so doing, he develops a thesis that Joyce’s attempt to capture the mysterious process whereby perception and consciousness are translated into language entails a fundamental challenge to everyday notions of reality. Joyce’s stylistic brilliance and virtuosity, his destruction of normal syntax and (...) meaning, “shock one into a new reality.” In the book’s final section, White examines the subtle relation between literary language and human consciousness and traces parallels between Joyce’s stylistic experimentation and Wittgenstein’s and Husserl’s ideas about language. (shrink)

David Lewis' objection to a generic theory of modality which he calls ‘magical ersatzism’ is that its linchpin, a relation he calls ‘selection’, must be either an internal or an external relation, and that this is unintelligible either way. But the problem he points out with classifying selection as internal is really just an instance of the general problem of how we manage to grasp underdetermined predicates, is not peculiar to magical ersatzism, and is amenable to some familiar solutions. (...) He provides no compelling grounds for thinking that classifying selection as external is unintelligible, and his argument has a false presupposition. I conclude that magical ersatzism is still a viable option in the metaphysics of modality. (shrink)

Little of the work in critical and hermeneutical psychology has been linked to instructional technology (IT). This article provides a discussion in order to fill the gap in this direction. The article presents a brief genealogy of American IT in relation to the influence of psychology. It also provides a critical and hermeneutical framework for psychology. It then discusses some problems of psychologism focusing on positivism, metaphysics, cultural ecology, and power. The narrow psychologism in IT produces a kind of systematic (...) blindness regarding cultural, political, and other issues. IT professionals are encouraged to engage reflectively with the power‐relations and ethical issues in which they are involved. The article points out a need for looking at psychology more comprehensively (e.g. critical and hermeneutical psychology). (shrink)

Why is America again unjustly at war? Why is its politics distorted by wedge issues like abortion and gay marriage? Why is anti-Semitism still so powerfully resurgent? Such contradictions within democracies arise from a patriarchal psychology still alive in our personal and political lives in tension with the equal voice that is the basis of democracy. This book joins a psychological approach with a political-theoretical one that traces both this psychology and resistance to it to the Roman Republic and Empire (...) and to three Latin masterpieces: Virgil's Aeneid, Apuleius's The Golden Ass, and Augustine's Confessions. In addition, this book explains many other aspects of our present situation including why movements of ethical resistance are often accompanied by a freeing of sexuality and why we are witnessing an aggressive fundamentalism at home and abroad. (shrink)

Why is America again unjustly at war? Why is its politics distorted by wedge issues like abortion and gay marriage? Why is anti-Semitism still so powerfully resurgent? Such contradictions within democracies arise from a patriarchal psychology still alive in our personal and political lives in tension with the equal voice that is the basis of democracy. This book joins a psychological approach with a political-theoretical one that traces both this psychology and resistance to it to the Roman Republic and Empire (...) and to three Latin masterpieces: Virgil's Aeneid, Apuleius's The Golden Ass, and Augustine's Confessions. In addition, this book explains many other aspects of our present situation including why movements of ethical resistance are often accompanied by a freeing of sexuality and why we are witnessing an aggressive fundamentalism at home and abroad. (shrink)

Why is America again unjustly at war? Why is its politics distorted by wedge issues like abortion and gay marriage? Why is anti-Semitism still so powerfully resurgent? Such contradictions within democracies arise from a patriarchal psychology still alive in our personal and political lives in tension with the equal voice that is the basis of democracy. This book joins a psychological approach with a political-theoretical one that traces both this psychology and resistance to it to the Roman Republic and Empire (...) and to three Latin masterpieces: Virgil's Aeneid, Apuleius's The Golden Ass, and Augustine's Confessions. In addition, this book explains many other aspects of our present situation including why movements of ethical resistance are often accompanied by a freeing of sexuality and why we are witnessing an aggressive fundamentalism at home and abroad. (shrink)

John Rawls is widely regarded as one of the most influential philosophers of the twentieth century, and his work has permanently shaped the nature and terms of moral and political philosophy, deploying a robust and specialized vocabulary that reaches beyond philosophy to political science, economics, sociology, and law. This volume is a complete and accessible guide to Rawls' vocabulary, with over 200 alphabetical encyclopaedic entries written by the world's leading Rawls scholars. From 'basic structure' to 'burdened society', from 'Sidgwick' to (...) 'strains of commitment', and from 'Nash point' to 'natural duties', the volume covers the entirety of Rawls' central ideas and terminology, with illuminating detail and careful cross-referencing. It will be an essential resource for students and scholars of Rawls, as well as for other readers in political philosophy, ethics, political science, sociology, international relations and law. (shrink)

To take up only the most beautiful, as yet to be made manifest in the realm of time and space, there are angels. These messengers who never remain enclosed in a place, who are also never immobile .... Endlessly reopening the enclosure of the universe, of universes, identities, the unfolding of actions, of history.The angel is that which unceasingly passes through the envelope(s) or container(s), goes from one side to the other, reworking every deadline, changing every decision, thwarting all repetition (...) ... they come' to herald the arrival of a new birth, a new morning. (Irigaray, ESD, 15)In the absence of civil laws positively defining their real rights and duties, the only criteria women have to refer to are subjective ones....But as long as there are no laws or rules which all women-and all men-may refer to and invoke when making their decisions, there can be no democracy, however attractive the immediate allegiance of a collectivity to a proposition may be. (Irigaray, ILTY, 1-2). (shrink)

wonder is the feeling of a philosopher, and philosophy begins in wonder. He was not a bad genealogist who said that Iris [the messenger of heaven] is the child of Thaumas [wonder].1 (Plato,Theaetetus, 155d)When our first encounter with some object surprises us and we find it novel, or very different from what we formerly knew or from what we supposed it ought to be, this causes us to wonder and to be astonished at it. . . . I regard (...) wonder as the first of all the passions. (Descartes, PS, 350)Wonder . . . is the passion of that which is already born and not yet reenveloped in love. . . . It is the passion of the first encounter. And of perpetual rebirth? . . . the place of incidence and junction of body and spirit, which has been covered over again and again, hardened through repetitions that hamper growth and flourishing (croissance et épanouissement [unfolding, blossoming])? . . . A third dimension. An intermediary. Neither the one nor the other. Which is not to say neutral or neuter. The forgotten ground of our condition between mortal and immortal, men andgods, creatures and creators. In us and among us. (Irigaray, ESD, 81–2). (shrink)

Why is America again unjustly at war? Why is its politics distorted by wedge issues like abortion and gay marriage? Why is anti-Semitism still so powerfully resurgent? Such contradictions within democracies arise from a patriarchal psychology still alive in our personal and political lives in tension with the equal voice that is the basis of democracy. This book joins a psychological approach with a political-theoretical one that traces both this psychology and resistance to it to the Roman Republic and Empire (...) and to three Latin masterpieces: Virgil's Aeneid, Apuleius's The Golden Ass, and Augustine's Confessions. In addition, this book explains many other aspects of our present situation including why movements of ethical resistance are often accompanied by a freeing of sexuality and why we are witnessing an aggressive fundamentalism at home and abroad. (shrink)

: Care work straddles the divide between activities performed out of love and those performed for pay. The tensions created for workers by this divide raise questions concerning connections between recognition and redistribution. Through an analysis of mobilization among childcare workers, we argue that care workers can address redistribution and recognition simultaneously through vocabularies of both skill and virtue. We conclude with a discussion of strategies to overcome the false dichotomy between recognition and redistribution.

In Conversations with Cinematographers, David Ellis has assembled interviews with some of the most influential and highly regarded cameramen of the last half century and more.

Chaïm Perelman, alone, and in collaboration with Lucie Olbrechts-Tyteca, developed the New Rhetoric Project, which is in use throughout the world. This book offers the first deep contextualization of the project’s origins and original translations of their work from French into English.

Concerns about business ethics have led many business schools to integrate ethics into the curriculum, with mixed results (May, Luth, & Schwoerer 2014, Wang & Calvano 2015, Waples, Antes, Murphy, Connelly & Mumford 2009). This paper seeks to improve our understanding of business students’ ethics by looking into their identity, a cognitive lens by which students see themselves and interpret their environment (Triandis 1989) and that can be relatively malleable to priming and socializing processes (Vignoles, Schwartz, & Luyckx 2011, Ybarra (...) & Trafimow 1998). Results show that undergraduate students with higher individual and lower collective identities report lower intentions to behave ethically. Moreover, our results show that a business education has the power to influence students’ ethical intentions by altering their individual and collective identities. Our results suggest that business schools should consider the effects of their curriculum and pedagogies on the development of individual and collective identities to educate more ethical business students. (shrink)

This book is an attempt to show how innovation in the "post-Google generation" is often catalyzed by those who cross a conventional line so firmly drawn between ...

We examine the compromises that are actually made in modern scientific discourse concerning atoms. We conclude that even the ideals of clarity and consistency can be legitimately compromised in order to obtain other advantages.