Calpain (Cp) is a calcium (Ca2+)‐dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon (...) tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca2+ can activate Cp molecules requiring μM to mM concentrations of Ca2+ for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell. BioEssays 28: 850–859, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Liberalism in Dark Times seeks to reconstruct an ethically oriented form of liberalism that is demanding, skeptical, and non-perfectionist. My friendly, astute interlocutors appropriately hold me t...

Michael Rosen’s The Shadow of God illustrates a distinctive way of understanding the relationship between ideas and history, while posing several connected questions. Among these are how the human condition of alienation may be overcome in a way that is ethically and intellectually defensible; how the search for reconciliation may generate, paradoxically, further alienation, and inspire terrible inhumanity; and whether a meaningful and good human life can be lived without the assurance of future justice—or, indeed, future existence. Rosen evokes the (...) emotional pull of the quest for reconciliation, and reveals the argumentative richness it has generated; yet reflection on human evil and suffering should chasten our aspirations to attain historical reconciliation or rational understanding. We may have good reason to turn away from both the project of theodicy, and the tendency to identify human value in something detached from living individuals, in favor of a reaffirmation of the value of the personal. Rosen’s own work illustrates how a reaffirmation of the personal, and respect for the freedom of others, may be practiced in and through the history of ideas. (shrink)

Today, liberals face a predicament: how to defend liberal principles, when adherence to them seems to constitute a fatal disadvantage against unprincipled opponents. The challenge is not new. In the early years of the twentieth century, liberalism was attacked, by critics on both the right and, especially, the left for being hypocritical, naïve, irresponsible, and impotent. It couldn't, for example (anti-liberalists thought), address the acute inequality of imperial rule, racial segregation, and socio-economic poverty. These issues of social justice it was (...) claimed by critics required a politics marked by an uncompromising commitment to ultimate ends, and an unrelenting use of power. Faced with such sentiments and the practical successes of anti-liberal ideologies (i.e. Fascism, Nazism, and Communism) liberals felt pressure to silence their scruples and doubts, and embrace the confidence, ruthlessness, and intransigence exhibited by their opponents. But doing so seemed tantamount to abandoning liberal hopes for, and commitments to, human freedom and all they valued in the first place. In Liberalism for Dark Times, Cherniss tells the story of the liberal response to this challenge in the twentieth century. Through a close study of five leading intellectuals engaged in these debates-Max Weber, Raymond Aron, Albert Camus, Reinhold Niebuhr, and Isaiah Berlin-Cherniss reconstructs a distinctive, neglected strand of liberal thought. This strand defines and defends liberalism as a political ethos: a complex of dispositions, temperament, and sensibility and style-which include skepticism; openness to experience; and careful, discriminating judgment-that shape how individuals make choices, meet challenges, understand and pursue possibilities, and conduct themselves toward others in the course of political struggle. In reconstructing the history of, what he calls, a tempered liberalism, and formulating it as a distinctive political perspective, Cherniss offers an alternative to the prevalent ways of thinking about both, liberalism's history and the intellectual resources available to it today. (shrink)

When reason leads to doubt -- The bridge of reason -- The foundation theory -- Testing ground -- Eternal power -- Purely actual -- Foundation of mind -- Foundation of matter -- Foundation of morals -- Foundation of reason -- Perfect foundation -- Challenging the bridge -- Removing barriers -- On the other side of the bridge.

Those most intimate with the works of H. Richard Niebuhr, who return to them time after time for theological and ethical sustenance, know that they exemplify a more interesting thinker than his brother, Reinhold. Of course, Reinhold was and remains the more public figure, read seriously in his time by politicians and theologians, celebrated by our current president, and enjoying renewed scholarly interest resulting in new editions of out-of-print works and a number of critical studies. Meanwhile, H. Richard continues to (...) exert decisive influence on American Protestant thought. Such diverse thinkers as Paul Ramsey, James Gustafson, Stanley Hauerwas, William Schweiker, Kathryn Tanner, Gordon Kaufman, Emilie Townes .. (shrink)

Placing politics in an ecological perspective that discerns an inextricable connection between human political agency and the forces of nonhuman nature would seem to be a difficult task. While we have grown accustomed to understanding our personal capacities for thought and action as well as the shape of our intimate relations as aspects of our natural inheritance, our political life and reflection remain rife with human exceptionalism. We understand animals to have rudimentary reasoning skills and physical capabilities incredible to us. (...) We also understand some animals gather in social groupings held together by mutual dependence for fulfilling affective needs. But it is difficult to imagine that animals have .. (shrink)

Isaiah Berlin was a central figure in twentieth-century political thought. This volume highlights Berlin's significance for contemporary readers, covering not only his writings on liberty and liberalism, the Enlightenment and Romanticism, Russian thinkers and pluralism, but also the implications of his thought for political theory, history, and the social sciences, as well as the ethical challenges confronting political actors, and the nature and importance of practical judgment for politics and scholarship. His name and work are inseparable from the revival of (...) political philosophy and the analysis of political extremism and defense of democratic liberalism following World War II. Berlin was primarily an essayist who spoke through commentary on other authors and, while his own commitments and allegiances are clear enough, much in his thought remains controversial. Berlin's work constitutes an unsystematic and incomplete, but nevertheless sweeping and profound, defense of political, ethical, and intellectual humanism in an anti-humanistic age. (shrink)

There is a thinking animal in your chair and you are the only thinking thing in your chair; therefore, you are an animal. So goes the main argument for animalism, the Thinking Animal Argument. But notice that there are many other things that might do our thinking: heads, brains, upper halves, left-hand complements, right-hand complements, and any other object that has our brain as a part. The abundance of candidates for the things that do our thinking is known as the (...) Thinking Parts Problem. Animalists who endorse the Thinking Animal Argument must solve this problem by giving reasons for privileging the animal over its rivals. In order to meet this challenge, some animalists have argued that the best solution is a biological minimalist one. In what follows, I argue that every extant biological minimalist solution to the Thinking Parts Problem fails. (shrink)

The present study investigates the importance of emotional disclosure and vulnerability in the production of hegemonic masculinities. Of particular interest is the role that silence and invisibility play in how men talk about recent stressful life events. One-on-one interviews with men who experienced a stressful life event in the past year illustrate how men often talk about these events in simultaneously visible and invisible ways. We use the term “cloudy visibility” to describe this engagement, identified both in terms of what (...) men articulate in relation to their past stressful experiences and how they articulate these experiences within the present moment of the interview. The conversational consequences of these linguistic devices are analyzed to illustrate how men obscure their inner emotional lives, thus reproducing hegemonic masculine ideals of staying strong and stoic in the face of adversity, while they also seek to make aspects of their inner lives seen and heard to an interviewer. (shrink)

A detailed study of Isaiah Berlin: historian, philosopher, and political theorist. Situates his evolving ideas in the context of British society and world politics. Offers a new interpretation of Berlin's influential writings on liberty and his debts to philosophy, and makes clear his relationship to the political debates of his times.

Many philosophers who do not analyze laws of nature as the axioms and theorems of the best deductive systems nevertheless believe that membership in those systems is evidence for being a law. This raises the question, “If the best systems analysis fails, what explains the fact that being a member of the best systems is evidence for being a law?” In this essay I answer this question on behalf of Leibniz. I argue that although Leibniz’s philosophy of laws is inconsistent (...) with the best systems analysis, his philosophy of nature’s perfection enables him to explain why membership in the best systems is evidence for being a law of nature. (shrink)

Necessary Existence breaks ground on one of the deepest questions anyone ever asks: why is there anything? Pruss and Rasmussen present an original defence of the hypothesis that there is a necessarily existing being capable of providing an ultimate foundation for the existence of all things.

The papers published in this issue of the EJPT discuss facets of the work of Isaiah Berlin from different perspectives and making use of varying intellectual approaches. At the same time, they focus attention on a few, central themes of Berlin's work: his complex relationship to liberalism and nationalism, his theories of liberty and value pluralism, and his perception and uses of the history of ideas. Consideration of the differences and overlap between these articles presents an occasion to take stock (...) of Berlin's work as a whole; and a critical response to the interpretations and criticisms of Berlin presented here afford an opportunity to re-evaluate, criticize and defend central aspects of Berlin's intellectual position. This article goes beyond summary to present a critical, interpretive adjudication between the claims of Berlin's work, and the interpretations of that work presented in the other articles in this issue. Drawing on each of these, I present an interpretation of Berlin's contributions to thinking about the Enlightenment, nationalism and cultural pluralism, utopianism and political ethics, liberty, and value pluralism; I also consider the difficulties of interpreting Berlin's work, and applying his ideas today. (shrink)

One issue in the debate about faith concerns the stance a religious person is committed to take on “God exists.” I argue that this stance is best understood as an assumption that God exists for the purpose of pursuing a good relationship with God. The notion of an “assumption for practical purpose” is distinguished from notions such as “belief” and “hope.” This stance is contrasted with others found in discussions of faith, and its ramifications for the problem of whether it (...) is rational to have faith are discussed. (shrink)

This book proposes that parties on both sides of this debate might shift their attention in a different direction, by focusing on the question of whether it is ...

This article argues that only a developmental approach-one that views Derrida's 1967 work on Husserl, La Voix et la phénomène, in light of Derrida's three earlier encounters with Husserl's work and recognizes significant differences among them-is able to resolve the bitter controversy that has lately surrounded Derrida's Husserl interpretation. After first reviewing the impasse reached in these debates, the need for "a new hermeneutics of deconstruction" is set out, and, then, the reasons why strong development has been rejected internal to (...) Derrida's corpus are discussed. After this, in a discussion of interest with respect to Husserl's own late teachings, as well as Derrida's standpoint, this article focuses on Derrida's 1962 "Introduction to Husserl's Origin." Against the prevailing interpretation, an argument is made showing that Derrida is much closer to Husserl's own positions than has been suspected, most importantly, in section VII of the "Introduction" where the theme of writing is first introduced. Thanks to this, that significant development in Derrida's thought does take place between 1962 and 1967 is demonstrated-and the present piece concludes by providing a brief sketch of the development of deconstruction overall as it came about through Derrida's repeated encounters with Husserlian phenomenology in the years 1954–67. (shrink)

Chief Executive Officers and other organizational leaders can affect how corporate social responsibility initiatives are perceived in their organizations. However, in order to be successful with regard to promoting CSR, leaders need to have strong network competencies and to move beyond charismatic leadership. In this paper we offer a critique of charismatic leadership as it relates to CSR, posit that the intellectual stimulation brought about by transformational leadership is more important in this regard, propose that internal and networking is a (...) leadership competence highly relevant to CSR, and emphasize the importance of working through highly credible opinion leaders in promoting CSR. (shrink)

Many have attempted to respond to arguments for the incompatibility of freedom with divine foreknowledge by claiming that God’s beliefs about the future are explained by what the world is like at that future time. We argue that this response adequately advances the discussion only if the theist is able to articulate a model of foreknowledge that is both clearly possible and compatible with freedom. We investigate various models the theist might articulate and argue that all of these models fail.

This paper discusses Maharal’s conception of the human being and its four major aspects, namely body, soul, intellect, and tselem (image or form). I suggest that some of his apparently inconsistent remarks concerning the human body may be reconciled by distinguishing two different senses of badness or evil. Secondly, I show that Maharal embraces what might be termed “moderate rationalism.” Thirdly, I elucidate his conception of the tselem by discussing parallel ideas in Kabbalistic literature.

We propose another positive illusion that fits with McKay & Dennett's (M&D's) criteria for adaptive misbeliefs. This illusion is pervasive in adult reasoning but we focus on its prevalence in children's developing theories. It is a strongly held conviction arising from normal functioning of the doxastic system that confers adaptive advantage on the individual.

Gilead et al.'s theory presupposes that traversing temporal, spatial, social, and hypothetical distances are largely interchangeable acts of mental travel that co-occur in human ontogeny. Yet, this claim is at odds with recent developmental data suggesting that children's reasoning is differentially affected by the dimension which they must traverse, and that different representational abilities underlie travel across different dimensions.

This paper addresses the potentially interactive effects of descriptive and injunctive norm perceptions on an unethical workplace behavior: counterproductive work behavior perpetration. We draw on the Focus Theory of Normative Conduct and its conceptual distinction between norm types to refine research on this topic. We also test a person-by-environment interaction to determine whether the interactive effects of these norms for CWB are enhanced among employees reporting a stronger need to belong to social groups. In two studies, predictors were assessed in (...) an initial survey and the dependent variable was assessed weeks later. Individuals employed across a range of industries served as participants. In Study 1, descriptive and injunctive norm perceptions of CWB interacted to predict CWB perpetration. This finding was replicated in Study 2. Additionally, Study 2 demonstrated that the interaction between the two norm types was especially strong among individuals high in NTB. Results suggest that to decrease CWB perpetration, organizations may profitably leverage the persuasive effects of “social norms marketing” to alter employee perceptions of the typicality and level of approval for CWBs. This is the first study to demonstrate that both descriptive and injunctive norm perceptions predict CWB perpetration. The demonstrated three-way interaction between the two norm types and NTB advances existing theory regarding the cognitive and motivational mechanisms underlying normative social influence. (shrink)

The name of the third author was incomplete in the initial online publication. The original article has been corrected.

This Editorial reports an exchange in form of a comment and reply on the article “History and Nature of the Jeffreys–Lindley Paradox” (Arch Hist Exact Sci 77:25, 2023) by Eric-Jan Wagenmakers and Alexander Ly.

In a pioneering book, Philosophy of Microbiology, Maureen O’Malley argues for the philosophical importance of microbes through an examination of their impact on ecosystems, evolution, biological classification, collaborative behavior, and multicellular organisms. She identifies many understudied conceptual issues in the study of microbes. If philosophers follow her lead, the philosophy of biology will be expanded and enriched.

Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet. However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a (...) historical outline of the “civilizing process” that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species. (shrink)

Shepard has argued that a universal law should govern generalization across different domains of perception and cognition, as well as across organisms from different species or even different planets. Starting with some basic assumptions about natural kinds, he derived an exponential decay function as the form of the universal generalization gradient, which accords strikingly well with a wide range of empirical data. However, his original formulation applied only to the ideal case of generalization from a single encountered stimulus to a (...) single novel stimulus, and for stimuli that can be represented as points in a continuous metric psychological space. Here we recast Shepard's theory in a more general Bayesian framework and show how this naturally extends his approach to the more realistic situation of generalizing from multiple consequential stimuli with arbitrary representational structure. Our framework also subsumes a version of Tversky's set-theoretic model of similarity, which is conventionally thought of as the primary alternative to Shepard's continuous metric space model of similarity and generalization. This unification allows us not only to draw deep parallels between the set-theoretic and spatial approaches, but also to significantly advance the explanatory power of set-theoretic models. Key Words: additive clustering; Bayesian inference; categorization; concept learning; contrast model; features; generalization; psychological space; similarity. (shrink)

Belief in souls is only one component of supernatural thinking in which individuals infer the presence of invisible mechanisms that explain events as paranormal rather than natural. We believe it is important to place greater emphasis on the prevalence of supernatural beliefs across other domains, if only to counter simplistic divisions between rationality and irrationality recently aligned with the contentious science/religion debate.

Cohen (2023) takes a fair and measured approach to the question of what ChatGPT means for bioethics. The hype cycles around AI often obscure the fact that ethicists have developed robust frameworks...

Decades of psychological research have been aimed at modeling how people learn features and categories. The empirical validation of these theories is often based on artificial stimuli with simple representations. Recently, deep neural networks have reached or surpassed human accuracy on tasks such as identifying objects in natural images. These networks learn representations of real‐world stimuli that can potentially be leveraged to capture psychological representations. We find that state‐of‐the‐art object classification networks provide surprisingly accurate predictions of human similarity judgments for (...) natural images, but they fail to capture some of the structure represented by people. We show that a simple transformation that corrects these discrepancies can be obtained through convex optimization. We use the resulting representations to predict the difficulty of learning novel categories of natural images. Our results extend the scope of psychological experiments and computational modeling by enabling tractable use of large natural stimulus sets. (shrink)