Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor (...) dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations. BioEssays 29:558–565, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Philosophy, science, and common sense all refer to propositions--things we believe and say, and things which are true or false. But there is no consensus on what sorts of things these entities are. Jeffrey C. King, Scott Soames, and Jeff Speaks argue that commitment to propositions is indispensable, and each defend their own views on the debate.

We consider how cue-reading, sensory-manipulation, and signaling games may initially evolve from ritualized decisions and how more complex games may evolve from simpler games by polymerization, template transfer, and modular composition. Modular composition is a process that combines simpler games into more complex games. Template transfer, a process by which a game is appropriated to a context other than the one in which it initially evolved, is one mechanism for modular composition. And polymerization is a particularly salient example of modular (...) composition where simpler games evolve to form more complex chains. We also consider how the evolution of new capacities by modular composition may be more efficient than evolving those capacities from basic decisions. (shrink)

In order for Bayesian inquiry to count as objective, one might argue that it must lead to a consensus among those who use it and share evidence, but presumably this is not enough. It has been proposed that one should also require that the consensus be reached from very different initial opinions by conditioning only on basic experimental evidence, evidence free from subjective, social, or psychological influence. I will argue here, however, that this notion of objectivity in Bayesian inquiry is (...) too narrow. (shrink)

Social theory between progress and apocalypse -- Autonomy and domination: Weber's cage -- Barbarism and modernity: Eisenstadt's regret -- Integration and justice: Parsons' utopia -- Despising others: Simmel's stranger -- Meaning evil -- De-civilizing the civil sphere -- Psychotherapy as central institution -- The frictions of modernity and their possible repair.

This chapter follows Lorenzo Magnani's observation that ongoing commercialization of science and academia impoverishes human potential for discovery. The chapter reviews Magnani on affordance, wonders what is accessible when "good" affordances appear absent, and answers self-affordance. Ecologies optimized for discovery should be optimized for self-affordance. The chapter considers the role of oracle as leading vision for discovery, and proposes a naturalized account of self that is essentially propositional, in pursuit of an inner oracle, seeking salvation through routine and religious ritual. (...) This is self-abduction. Variable biological development may motivate religious self-abduction characterized by self-sacrifice for the collective good over the long term. in conclusion, the chapter affirms Magnani's call to optimize cognitive ecologies for discovery, by prioritizing religious self-abduction. (shrink)

We consider the efficacy of various forms of reinforcement learning with punishment in evolving linguistic conventions in the context of Lewis-Skyrms signalling games. We show that the learning strategy of reinforcement with iterative punishment is highly effective at evolving optimal conventions in even complex signalling games. It is also robust and can be easily extended to a self-tuning variety of reinforcement learning. We briefly discuss some of the virtues of reinforcement with iterative punishment and how it may be related to (...) learning in nature. (shrink)

A simple tool is provided to assist researchers in assessing contributions to a scientific publication, for ease in evaluating which contributors qualify for authorship, and in what order the authors should be listed. The tool identifies four phases of activity leading to a publication—Conception and Design, Data Acquisition, Analysis and Interpretation, and Manuscript Preparation. By comparing a project participant’s contribution in a given phase to several specified thresholds, a score of up to five points can be assigned; the contributor’s scores (...) in all four phases are summed to yield a total “contribution score”, which is compared to a threshold to determine which contributors merit authorship. This tool may be useful in a variety of contexts in which a systematic approach to authorial credit is desired. (shrink)

Richard Dawkins’s The Blind Watchmaker argues that evolution is a blind, mechanistic process devoid of purpose or intelligence. This paper provides a complete and total refutation of Dawkins’s claims using Aristotelian metaphysics and Ethical Empirical Rationalism (EER), a doctrine that integrates empirical truth, rational coherence, and ethical universality. Through a focus on Dawkins’s three primary errors, this paper demonstrates how Aristotle’s concepts of form, purpose, and agency offer a superior framework for understanding evolution. Using Cognita as an illustration, this paper (...) highlights how EER establishes a coherent, truth-centered approach to nature, in contrast to Dawkins’s reductionist perspective. (shrink)

As social theorists seek to understand the contemporary challenges of radical populism, we would do well to reconsider the febrile insights of the psychoanalytic social theorist Erich Fromm. It was Fromm who, at the beginning of the 1930s, conceptualized the emotional and sociological roots of a new ‘authoritarian character’ who was meek in the face of great power above and ruthless to the powerless below. It was Fromm, in the 1950s, who argued that societies, not only individuals, could be sick. (...) This essay traces the intertwining of psychoanalytic and sociological methods that allowed Fromm to create such new ideas. At the same time, it highlights how Fromm’s sociology was hampered by an economistic Marxist approach to the institutions and culture of democratic capitalist societies. Such theoretical restriction prevented Fromm from conceptualizing how institutions like democracy, science, and psychotherapy can provide resources for widespread emotional recuperation and civil repair. (shrink)

Digital Health Technologies (DHTs) are currently the subject of much debate both in terms of their technological frontiers as well as their ethical, legal and societal implications (ELSI). Regulation of such technologies as medical devices currently lacks behind their level of adoption. Digital Twins are the next evolution step of such DHTs and provide an opportunity to anticipate and act on ELSI before adoption again leaps before the necessary review. This paper introduces the concept and use cases of digital twins (...) in medicine, then frames the debate through the lens of related technologies, machine learning and personalized medicine, and maps ethical challenges stemming from those. Finally, we lay out how digital twins may change and challenge the future practice of medicine. (shrink)

Levinas and the Philosophy of Religion Jeffrey L. Kosky Reveals the interplay of phenomenology and religion in Levinas’s thought. "Kosky examines Levinas’s thought from the perspective of the philosophy of religion and he does so in a way that is attentive to the philosophical nuances of Levinas’s argument.... an insightful, well written, and carefully documented study... that uniquely illuminates Levinas’s work." —John D. Caputo For readers who suspect there is no place for religion and morality in postmodern philosophy, (...) class='Hi'>Jeffrey L. Kosky suggests otherwise in this skillful interpretation of the ethical and religious dimensions of Emmanuel Levinas’s thought. Placing Levinas in relation to Hegel and Nietzsche, Husserl and Heidegger, Derrida and Marion, Kosky develops religious themes found in Levinas’s work and offers a way to think and speak about ethics and morality within the horizons of contemporary philosophy of religion. Kosky embraces the entire scope of Levinas’s writings, from Totality and Infinity to Otherwise than Being, contrasting Levinas’s early religious and moral thought with that of his later works while exploring the nature of phenomenological reduction, the relation of religion and philosophy, the question of whether Levinas can be considered a Jewish thinker, and the religious and theological import of Levinas’s phenomenology. Kosky stresses that Levinas is first and foremost a phenomenologist and that the relationship between religion and philosophy in his ethics should cast doubt on the assumption that a natural or inevitable link exists between deconstruction and atheism. Jeffrey L. Kosky is translator of On Descartes’ Metaphysical Prism: The Constitution and the Limits of Onto-theo-logy in Cartesian Thought by Jean-Luc Marion. He has taught at Williams College. Indiana Series in the Philosophy of Religion—Merold Westphal, general editor May 2001 272 pages, 6 1/8 x 9 1/4, bibl., index, append. cloth 0-253-33925-1 $39.95 s / £30.50. (shrink)

If truth hurts, this is no doubt because it is often enough forced on us. And the question as to whether the reception of “nice,” “easy” truths is similarly an outcome of coercion negates itself in its very formulation — we do not ask “why are things the way they are?” from a feeling of comfort; the plaintiff cry of “how, then, shall we live?” does not come to us out of a sense of security. Indeed, insofar as truth overtakes (...) us and interrupts the conventions of our lives, it occurs to us quite apart from our ordinary desires and wants. We are thus faced with a paradox: what claim can truth make on a bein g that “doesn’t need it and doesn’t care about it—since it doesn’t at all concern his needs”? When one considers that the awareness of truth is indexed to lived experience, the paradox is only heightened. (shrink)

This review explores a recent trend in commentary on Hegel’s philosophy of history which owes much of its interpretive substance to the aesthetic modernism of the Frankfurt School. This modernist trend emphasizes the interplay of form and content, material conditions of rationality, and the temporal disjunction between experiencing and cognizing history. In so doing, it produces a deeply political, psychoanalytic, and musical reading of Hegel.

The immune system can generate an almost infinite number of different antibody specificities, the sum of which is the antibody repertoire. This article considers aspects of the mechanism and control of immunoglobulin variable (V) region gene assembly with a focus on how these factors may affect generation of the antibody repertoire in normal and disease states. New model systems to study the mechanism and control of V gene assembly are described, in particular the introduction of V gene recombination substrates into (...) Abelson murine leukemia virus‐transformed pre‐B cells. Finally, a model is presented which suggests that control of V gene assembly is mediated by regulating accessibility of substrate gene segments to recombinational machinery. (shrink)

The early Greek Stoics were the first philosophers to recognize the object of normal human perception as predicative or propositional in nature. Fundamentally we do not perceive qualities or things, but situations and things happening, facts. To mark their difference from Plato and Aristotle, the Stoics adopted phantasia as their word for perception.

Individual scapetribing is identified as pointing the finger of blame at organizations (or groups, institutions, and systems) as a means of excusing or inaccurately ascribing responsibility for one's own actions and their consequences. This type of behavior is shown to be related to corporate scape-goating as described by Wilson (1993). The paper addresses responsibility ascriptions and the importance of corporate responsibility as a significantly influential multi-person system.

The incorporation of Plato into the current OCR Classical Civilisation A Level syllabus, as part of the Love and Relationships topic (LR) presents a challenge for the classroom teacher. While the specification makes study of Plato mandatory the content description in practice effectively relegates the topic to the side-lines. Having described this problem the article goes on to suggest how Plato’s ideas can be taught within the framework of the existing specification in a pupil-friendly manner which is true to the (...) spirit of Plato’s own philosophical practice. (shrink)

The construction of geometrical concepts is familiar to readers of Kant’s _Critique of Pure Reason_ and _Prolegomena_ as the “shining example” [_glänzendes Beispiel_] of a priori cognition. So when Kant begins to offer constructions of concepts in physics in the _Metaphysical Foundations of Natural Science_, it seems unproblematic that mathematics is being applied to matter in motion. Much of Kant’s rhetoric suggests that nothing extraordinary is going on. And yet, constructions in Kant’s philosophy of physics display such peculiarities in comparison (...) to mathematical ones that they begin to seem like unfamiliar operations, distinct from constructions in pure mathematics. (shrink)

Natural resource management agencies in the United States have a legal responsibility to represent Indigenous Peoples and federally recognized Tribes in environmental stewardship. This comment article is a call to action that argues for genuine representation of Tribes and other Indigenous Peoples through adherence to existing, formal consultation policies and coproduction of knowledge. Agencies must recognize and respect the differences between public involvement and government-to-government consultation with federally-recognized Tribes. Sovereign tribal nations are not the public and have a unique relationship (...) with federal agencies based in the federal trust responsibility. Coproduction of knowledge is an emerging enterprise that has potential for meaningfully engaging and genuinely and equitably representing Indigenous Peoples and Tribes and should be codeveloped and implemented as policy. Agencies should build capacity to properly represent tribal nations in decisions. Agency employees and Indigenous Peoples must spend more time together to increase cultural awareness and build meaningful relationships to facilitate genuine consultation and coproduction of knowledge. (shrink)

L’année 2005 marque le centenaire de la naissance de Jean-Paul Sartre. Conçu à l’occasion de cet anniversaire, le présent numéro est consacré à l’étude de l’œuvre de Sartre dans les différents champs où elle s’est aventurée, de la philosophie à la littérature, de la psychologie à la politique. Loin d’avoir l’ambition de mesurer précisément la..

Because of the measurement problem, the standard theory of quantum mechanics is at best incomplete and at worst logically inconsistent. Everett suggested that the measurement problem could be resolved by taking the linear dynamics to be a complete and accurate description of the time-evolution of every physical system. The purpose of this dissertation is to see what happens when one takes Everett's proposal seriously. This dissertation includes a discussion of the standard theory of quantum mechanics and its origins, the measurement (...) problem, Everett's relative-state formulation, the many-worlds interpretation, Albert's bare theory and its suggestive properties, and Albert and Loewer's single-mind and many-minds theories. I will show how one might construct a theory that exploits the bare theory's suggestive properties without encountering its empirical problems. (shrink)

Kant repeatedly uses the biangle as an example of an impossible figure. In this paper, I offer an account of these passages and their significance for the possibility of geometry as a science. According to Kant, the constructibility of the biangle would signal the failure of geometry. Whereas Wolff derives the no-biangle proposition from the axiom that between two points there can be only one straight line, Kant gives it axiomatic status as a synthetic a priori principle possessing immediate certainty. (...) Because we are unable to generate a schema for the biangle, the failure of the attempt to construct it is intuitively clear. The parallel between mathematical and empirical concepts is instructive because both involve the synthesis of disparate intuitions into a unity. We do not, strictly speaking, even possess a well-formed concept of the biangle, because its representation cannot fulfill certain basic requirements of concept formation. (shrink)

In this introduction to Part 1 of “Contextualism—the Next Generation: Symposium on the Future of a Methodology,” the editor of Common Knowledge, a “journal of left-wing Kuhnian opinion,” reports that the new symposium responds to contextualist criticism of the previous CK symposium, which was on xenophilia. The content of the earlier symposium met with objections, from contextualists, on the grounds of methodology, and the new symposium questions the methodology of contextualism for the limits that it places on content as well (...) as on normative aims and degree of focus. Tracing the origins of contextualism to Kuhn and his theory that paradigms of scientific knowledge are incommensurable, this essay then argues that Kuhnian method is formal, with scant concern for content, and that Kuhn’s work was vatic, more than philosophical or historical. Kuhn’s depiction of his sudden, blinding realization that Aristotelian physics is correct in its own context is assessed as an ironic application of biblical scenes of revelation to what is, essentially, a process of scrupulous, piecemeal scholarship. What Kuhn unknowingly wanted, the essay concludes, was a combination of contextualism and phenomenology, as a means of knowing what it was like to believe in Aristotelian, as opposed to modern, concepts of matter, quality, space, void, position, change, and motion. The essay then introduces the first contribution to the new symposium: a monograph retrieving geometrical and taxonomic—Euclidean and Theophrastan—idioms of discourse about fictional characters and inquiring into their changing affective content. (shrink)

“The Zadeh Scenario,” when taken together with the subsequent layers of peer review and commentary on that peer review, highlights two crucial insights regarding peer review for clinical ethics. The first is one that most of Finder’s peer reviewers miss: peer-reviewers who would give attestation to quality need to be critically attentive to, and reflective about, the evidence supplied to them by candidates. The second is a more significant point: the kind of doing that is clinical ethics consultation is a (...) local form of moral enquiry, seeking not just to achieve medical – or clinical ethical – goals, but to enact human goods. Good peer review thus turns on being clear regarding the goods of ethics consultation. Buried inside “The Zadeh Scenario” one can find several goods of clinical ethics. These goods are subjective, idiosyncratically named and defined by patients, and embedded in an institution of healthcare that purports to be of service to the goods of health. The clinical ethics consultant, at her best, acts as a careful mid-wife, attempting to bring forth the goods desired, the goods possible, and perhaps even the goods that, while desired, are not possible. After all, some goods pursued by patients are not possible due to the limits of medicine. On the other hand, some goods pursued by medicine are not desired by patients. And equally, some goods pursued by clinical ethicists might be limited, provisional, and local. “The Zadeh Scenario” thus acts to problematize the goals of clinical ethics consultation, asking it to focus on the goods that the practice might bring forth. (shrink)

Only through a long series of accidents do we have “The Works of Aristotle” at all—the Corpus Aristotelicum. When Aristotle died in 322 B.C., he is said to have left behind a body of 156 “published” works (“exoteric,” namely, available for public consumption). They survive only in fragments, too short and too few to give much sense of them. That his esoteric works, the Corpus Aristotelicum, have survived at all has been called “miraculous.” This paper traces how those esoteric works (...) of Aristotle were transmitted over the next eighteen hundred years. My claim is that this transmission depended upon communities that kept these works of Aristotle “in print.” Further, those communities can often only be inferred, like the description of the substantial object from what is known only by its shadow. The paper concludes with reflections on the tenuous existence of historic texts and how the digital age may further threaten transmission of knowledge from the past to communities in the future. I propose that the transmission history of Aristotle’s texts may provide signposts that guide us both in handing down knowledge to future generations as well as in finding models for promoting knowledge and for establishing communities of diversity. (shrink)

There is good reason to suppose that our best physical theories are false: In addition to its own internal problems, the standard formulation of quantum mechanics is logically incompatible with special relativity. There is also good reason to suppose that we have no concrete idea concerning what it might mean to claim that these theories are approximately or vaguely true. I will argue that providing a concrete understanding the approximate or vague truth of our current physical theories is not a (...) task for traditional epistemology; rather, this is only possible in the context of ongoing empirical inquiry. [Note #1]. (shrink)

In this introduction to part 3 of the Common Knowledge symposium “Antipolitics,” the journal's editor argues that, apart from sortition, the best guarantees of safety in a democracy are, first, to augment judicial oversight of all political processes and, second, to exclude politicians from the process of selecting judges. “There can never be too much judicial interference,” he writes, “in what politicians regard as their domain.” The author reached this conclusion during attempts by the newly elected Israeli government, in the (...) spring of 2023, to make itself absolute by eliminating checks on its conduct that the Supreme Court had been developing and applying since the 1950s. Traditional Jewry and Judaism being notoriously hypernomian, the resistance to legality on the part of the ruling coalition has conveyed an aura of antinomian heresy. The choice in Israel appears to be between antipolitics and antinomianism, rather than between Left and Right politically—and the antipolitical model in Israel of a superintendent judiciary and an autonomous attorney general is arguably superior to the American prototype, even from the perspective (“all men are created equal..., endowed by their Creator with certain unalienable Rights”) that we have come to regard as quintessentially American. (shrink)

Achieving a high quality of life is dependent upon how individuals face adversity. Positive psychological interventions are well-suited to support coping efforts; however, experimental research is limited. The purpose of the current research was to examine whether different savoring interventions could increase important coping resources in response to a social-evaluative hassle. We completed an experimental mixed subject design study with a university student sample. All participants completed a hassle induction task and were then randomly assigned into different intervention groups. Positive (...) emotion ratings were collected at three points in time. Results revealed a significant time x intervention interaction effect, such that individuals in the savoring the moment intervention reported higher levels of positive emotions compared to individuals assigned to the true control group, guided imagery control group, and savoring through reminiscence intervention. Such findings represent a significant extension to savoring theory and offer support for savoring the moment exercises as a primary prevention strategy to bolster effective responses to social-evaluative hassles. (shrink)