Multidrug resistance resulting from expression of an energy‐dependent drug efflux pump encoded by the human MDR1 gene is a major impediment to effective cancer therapy. Pharmacologic intervention aimed at inhibiting this multidrug transporter should improve existing chemotherapy of human cancer, but drug development has been delayed by the difficulty and expense of developing valid animal models. Using recombinant DNA technology, a transgenic mouse has been engineered whose bone marrow is protected from the toxic effects of chemotherapy by expression of the (...) MDR1 gene. This animal system allows the rapid screening of drugs which inhibit the multidrug transporter and heralds a new era of using transgenic animals for pharmacologic screening. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Dewey, Implementation, and Creating a Democratic Civic UniversityIra HarkavyThinking begins in... a forked-road situation, a situation that is ambiguous, that presents a dilemma, that poses alternatives.—John Dewey (How We Think 122)The social philosopher, dwelling in the region of his concepts, “solves” problems by showing the relationship of ideas, instead of helping men solve problems in the concrete by supplying them hypotheses to be used and tested in projects of (...) reform.—John Dewey (Reconstruction in Philosophy 192)Democracy must begin at home, and its home is the neighborly community.—John Dewey (The Public and Its Problems 213)democracy, as we all know, is seriously threatened throughout the world (Fisher). In the United States, the chasm-like inequities laid bare by COVID-19, the ongoing killing of black Americans, the violent insurrection at the Capitol, and the continuing attempt to subvert the electoral process are powerful indicators of a system under severe strain (Guardian Staff; Rubin). These developments are also a sign of deep and chronic problems, including the following:1. Increasing economic, political, social, educational, and health inequalities2. Increasing racism, anti-Semitism, and xenophobia3. Increasing attacks on science, knowledge, and democracy itself4. Declining trust in nearly all major institutionsMany things, obviously, contribute to the present situation. Among them is the failure of universities to successfully do what they are supposed to do: educate students to be ethical, empathetic, engaged, democratic citizens, and [End Page 49] advance knowledge for the continuous betterment of the human condition (Benson et al., Knowledge). To use a Marxian framework, but to reject its economic determinism, universities, in my judgment, are not a part of society’s superstructure. They are, to the contrary, a core component of its base (Marx, “Preface”). What they do matters enormously, significantly determining the kind of society we have now and will have in the future.Universities, as former Harvard president Derek Bok and others have emphasized, have become the central societal institutions in the world (Bok, Universities and the Future 3). Research universities, in my judgment, are the most central. They develop new ideas and technologies, incubate businesses, serve as cultural and artistic centers, and are engines of local, national, and global economies. As anchor institutions, they often engage in partnerships with government, the private sector, and community-based organizations to revitalize local neighborhoods and schools (“Anchor Institutions Task Force”). It is the university’s role as an educational institution, however, that is most important.The schooling system increasingly functions as the core subsystem—the strategic subsystem—of modern information societies. Schooling, more than any other subsystem, as John Dewey claimed, influences the functioning of the societal system as a whole. Viewed systemically, it has on balance the greatest “multiplier” effects, direct and indirect, short-term and long-term. Restating these points somewhat differently, I strongly agree with the Chilean sociologist Eugenio Tironi that the answer to the question “What kind of education do we need?” is to be found in the answer to the question “What kind of society do we want?” (Tironi). Education and society are dynamically interactive and interdependent. If human beings hope to maintain and develop a particular type of society, they must develop and maintain the particular type of education system conducive to it. As Dewey in effect argued: No effective democratic schooling system, no democratic society.1For William Rainey Harper, who, as the first president of the University of Chicago, brought Dewey to Chicago, universities are the primary shapers of the American schooling system. In an 1899 speech at the University of California, he perceptively observed that “[t]he school system, the character of which, in spite of itself, the university determines and in a large measure controls.... [T]hrough the school system every family in this entire broad land of ours is brought into touch with the university; for from it proceed the teachers or the teachers’ teachers” (Harper 25). Agreeing with Harper, I contend that higher education institutions powerfully shape the learning, values, and aspirations of students from kindergarten through graduate school. [End Page 50]Given the university’s societal role and influence, creating and sustaining an inclusive, just democratic society requires a... (shrink)

In the wake of business scandals at Enron, Arthur Andersen, Global Crossing, Tyco—the list grows daily—there is an increasing sense among employees, executives, investors, and the public that the “anything goes” culture of the New Economy is over. Today, businesses must act responsibly, transparently, and with integrity. Using in-depth case studies and examples from over 50 companies that range from Starbucks to Citigroup, General Motors to General Electric, DuPont to Dell, Ira A. Jackson, former director of the Center for Business (...) and Government at Harvard’s Kennedy School, shows the quantifiable and enduring business advantage to “doing the right thing.” Companies that give back to their employees and society—focusing on values and purpose as well as profitability—often gain commpetitive advantage and improve their brand image, consumer loyalty, and employee satisfaction. Identifying seven principles of making values integral to business processes and practices, PROFITS WITH PRINCIPLES opens the door to a new kind of capitalism, providing a wealth of practical recommendations companies of all sizes can model their own efforts after. (shrink)

A conversational implicature is an inference that consists in attributing to a speaker an implicit meaning that goes beyond the explicit linguistic meaning of an utterance. This paper experimentallyinvestigates scalar implicature, a paradigmatic case of implicature in which a speaker's use of a term like Some indicates that the speaker had reasons not to use a more informative one from the samescale, e.g. All; thus, Some implicates Not all. Pragmatic theorists like Grice would predict that a pragmatic interpretation is determined (...) only after its explicit, logical meaning is incorporated (e.g. whereSome means at least one). The present work aims to developmentally unpack this prediction by showing how younger, albeit competent, reasoners initially treat a relatively weak term logically beforebecoming aware of its pragmatic potential. Three experiments are presented. Experiment 1 presents a modal reasoning scenario offering an exhaustive set of conclusions; critical among these isparticipants' evaluation of a statement expressing Might be x when the context indicates that the stronger Must be x is true. The conversationally-infelicitous Might be x can be understood logically(e.g. as compatible with Must) or pragmatically (as exclusive to must). Results from five-, seven-, and nine-year-olds as well as adults revealed that a) seven-year-olds are the youngest to demonstratemodal competence overall and that; b) seven- and nine-year-olds treat the infelicitous Might logically significantly more often than adults do. Experiment 2 showed how training with the modal taskcan suspend the implicatures for adults. Experiment 3 provides converging evidence of the developmental pragmatic effect with the French existential quantifier Certains (Some). Whilelinguistically-sophisticated children (eight- and ten-year-olds olds) typically treat Certains as compatible with Tous (All), adults are equivocal. These results, which are consistent with unanticipatedfindings in classic developmental papers, reveal a consistent ordering in which representations of weak scalar terms tend to be treated logically by young competent participants and morepragmatically by older ones. This work is also relevant to the treatment of scalar implicatures in the reasoning literature. (shrink)

Emotions can be understood as a coherent, integrated system of general-purpose coping strategies, guided by appraisal, for responding to situations of crisis and opportunity (when specific-purpose motivational systems may be less effective). This perspective offers functional explanations for the presence of particular emotions in the emotion repertoire, and their elicitation by particular appraisal combinations. Implications of the Emotion System model for debated issues, such as the dimensional vs. discrete nature of appraisals and emotions, are also discussed.

Researchers have found undeniable variability and irrefutable evidence of consistencies in emotional responses across situations, individuals, and cultures. Both must be acknowledged in constructing adequate, enduring models of emotional phenomena. In this article I outline an empirically-grounded model of the structure of the emotion system, in which relatively variable actions may be used to pursue relatively consistent goals within discrete emotion syndromes; the syndromes form a stable, coherent set of strategies for coping with crises and opportunities. I also discuss a (...) framework that can integrate dimensional and discrete perspectives on emotions. (shrink)

Mixed emotions are conceptualized as involving the co-occurrence of states opposite in valence. One might expect that combinations of opposites would show diminished overall emotion intensity. But is this always the case? If not, when will mixed emotions be characterized by high intensity, and when by low intensity? In this article, theories of emotion-eliciting appraisal and emotion intensity are employed to understand mixed emotions and phenomena of passion. It is proposed that intense emotions are produced by transformative events: perceived motive-relevant (...) changes that are important, large, and rapid. Transformative events that can move a person between greatly motive-inconsistent and greatly motive-consistent outcomes constitute one potent path to passion. Illustrative phenomena of passion, mixed emotions, and related research are discussed. (shrink)

Lewisian Genuine Realism about possible worlds is often deemed unable to accommodate impossible worlds and reap the benefits that these bestow to rival theories. This thesis explores two alternative extensions of GR into the terrain of impossible worlds. It is divided in six chapters. Chapter I outlines Lewis’ theory, the motivations for impossible worlds, and the central problem that such worlds present for GR: How can GR even understand the notion of an impossible world, given Lewis’ reductive theoretical framework? Since (...) the desideratum is to incorporate impossible worlds into GR without compromising Lewis’ reductive analysis of modality, Chapter II defends that analysis against objections. The rest of the thesis is devoted to incorporating impossible worlds into GR. Chapter III explores GR-friendly impossible worlds in the form of set-theoretic constructions out of genuine possibilia. Then, Chapters IV-VI venture into concrete impossible worlds. Chapter IV addresses Lewis’ objection against such worlds, to the effect that contradictions true at impossible worlds amount to true contradictions tout court. I argue that even if so, the relevant contradictions are only ever about the non-actual, and that Lewis’ argument relies on a premise that cannot be nonquestion- beggingly upheld in the face of genuine impossible worlds in any case. Chapter V proposes that Lewis’ reductive analysis can be preserved, even in the face of genuine impossibilia, if we differentiate the impossible from the possible by means of accessibility relations, understood non-modally in terms of similarity. Finally, Chapter VI counters objections to the effect that there are certain impossibilities, formulated in Lewis’ theoretical language, which genuine impossibilia should, but cannot, represent. I conclude that Genuine Realism is still very much in the running when the discussion turns to impossible worlds. (shrink)

Several theists have adopted a position known as ‘sceptical theism ’, according to which God is justified in allowing suffering, but the justification is often beyond human comprehension. A problem for sceptical theism is that if there are unknown justifications for suffering, then we cannot know whether it is right for a human being to relieve suffering. After examining several proposed solutions to this problem, I conclude that one who is committed to a revealed religion has a simpler and more (...) effective solution. In particular, according to traditional Judaism, God has permitted us, indeed commanded us, to relieve suffering, so we know that it is right for us to do so. I further show how God's command, according to Judaism, that we save lives provides an answer to an analogous argument put forward by David Hume. Thus, revealed theistic religions can sometimes solve problems more effectively than theism alone. (shrink)

Giving Voice to Values as a Professional Physician provides students with the theoretical background and practical applications for acting on their values in situations of ethical conflict. It is the first medical ethics book that utilizes the Giving Voice to Values methodology to instruct students in medical ethics and professionalism. In doing so, it shifts the focus of ethics education from intellectually examining ethical theories and conflicts to emphasizing moral action. Each section of the book explains how moral decision-making and (...) action can be implemented in the healthcare arena. Medical ethics cases are provided throughout in order to assist students in giving voice to their values and developing skills for professional action. The Giving Voice to Values methodology, and the cases in this book, do not focus on the big questions of academic ethics, but rather on the ethics of the everyday, even if the challenges presented are difficult. In other words, the ethical questions students will have to face, in this book and in medical education and practice, are about how to interact with others, whether they be patients or colleagues, who might have different ethical positions. The book provides a unique guide for professional identity formation and the teaching of ethics in medical schools. (shrink)

ABSTRACT Two rival approaches to property rights dominate contemporary political philosophy: Lockean natural rights and egalitarian theories of distributive justice. This article defends a third approach, which can be traced to the work of David Hume. Unlike Lockean rights, Humean property rights are not grounded in pre-institutional moral entitlements. In contrast to the egalitarian approach, which begins with highly abstract principles of distributive justice, Humean theory starts with simple property conventions and shows how more complex institutions can be justified against (...) a background of settled property rights. Property rights allow people to coordinate their use of scarce resources. For property rules to serve this function effectively, certain questions must be considered settled. Treating existing property entitlements as having prima facie validity facilitates cooperation between people who disagree about distributive justice. Lockean and egalitarian theories endorse moral claims that threaten to unsettle property conventions and undermine social cooperation. (shrink)

In this major intellectual history, Ira Katznelson examines the works of Hannah Arendt, Robert Dahl, Richard Hofstadter, Harold Lasswell, Charles Lindblom, Karl Polanyi, and David Truman, detailing their engagement with the larger project of reclaiming the West's moral bearing.

This paper studies the relationship of Artificial Intelligence to the study of language and the representation of the underlying knowledge which supports the comprehension process. It develops the view that intelligence is based on the ability to use large amounts of diverse kinds of knowledge in procedural ways, rather than on the possession of a few general and uniform principles. The paper also provides a unifying thread to a variety of recent approaches to natural language comprehension. We conclude with a (...) brief discussion of how Artificial Intelligence may have a radical impact on education if the principles which it utilizes to explore the representation and use of knowledge are made available to the student to use in his own learning experiences. (shrink)

Peter van Inwagen's Direct Argument (DA) for incompatibilism purports to establish incompatibilism with respect to moral responsibility and determinism without appealing to assumptions that compatibilists usually consider controversial. Recently, Michael McKenna has presented a novel critique of DA. McKenna's critique raises important issues about philosophical dialectics. In this article, we address those issues and contend that his argument does not succeed.

In her (1996) Kadri Vihvelin argues that autoinfanticide is nomologically impossible and so that there is no sense in which time travelers are able to commit it. In response, Theodore Sider (2002) defends the original Lewisian verdict (Lewis 1976) whereby, on a common understanding of ability, time travelers are able to kill their earlier selves and their failure to do so is merely coincidental. This paper constitutes a critical note on arguments put forward by both Sider and Vihvelin. I argue (...) that although Sider’s criticism starts out promisingly he doesn’t succeed in establishing that Vihvelin’s analysis fails, because (a) he neglects to rule out a class of counterfactuals to which Vihvelin’s sample-case may belong; and (b) (together with Lewis) he is wrong to suggest that future facts are irrelevant in the evaluation of time travelers’ abilities. I show instead that Vihvelin’s argument is viciously circular, indicating that even if there are nomological constraints on autoinfanticide these cannot be established a priori. (shrink)

We describe an experiment that investigated levels-of-processing effects in recognition memory for famous faces. The degree of conscious control over the recognition decisions was manipulated by using a response deadline procedure, and memory awareness associated with those decisions was assessed using a standard remember-know paradigm. Levels-of-processing effects were found at both short and long response deadlines, and at both deadlines those effects occurred only in remembering. Moreover, knowing, as well as remembering, increased with the greater opportunity for conscious control over (...) recognition decisions at the long deadline. These results have implications for dual-process theories that distinguish between a slower, more controlled recollection process, reflected in remembering, and a faster, more automatic familiarity process, reflected in knowing. (shrink)

The connective or can be treated as an inclusive disjunction or else as an exclusive disjunction. Although researchers are aware of this distinction, few have examined the conditions under which each interpretation should be anticipated. Based on linguistic-pragmatic analyses, we assume that interpretations are initially inclusive before either (a) remaining so, or (b) becoming exclusive by way of an implicature ( but not both ). We point to a class of situations that ought to predispose disjunctions to inclusive interpretations and (...) to situations that encourage exclusive interpretations. A disjunction's ultimate interpretation is based on its potential informativeness, where the interpretation of the disjunctive utterance having the smallest number of true conditions is considered most informative. Our investigation leads to five experiments employing arbitrary materials. Among the problems expected to encourage inclusive interpretations are those that present disjunctions in the antecedents of conditionals and in question forms. The best candidates to produce implicatures are those disjunctions that underdetermine an expected conjunctive conclusion, although other disjunctive utterances that are more informative as exclusive are discussed and tested. (shrink)

This paper explores two aspects of Hume's skeptical crisis in the conclusion to _Treatise<D> Book I: his involved personal experience of the crisis, and his detached naturalistic reflection on it. I discuss several distinct states of mind reported in the text, ranging from extreme skepticism that rejects all belief, to natural dogmatism that rejects all reflection, to mitigated skepticism that tries to reconcile reflection and belief. I argue against interpretations according to which Hume's skepticism supports his naturalism, and I suggest (...) that Hume's extreme skepticism ultimately depends on a predisposition to think of the crucial elements of human cognition as "trivial", as epistemically disabling rather than enabling. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Hume Studies Volume 30, Number 1, April 2004, pp. 33-50 Constancy, Coherence, and Causality IRA M. SCHNALL According to David Hume, we believe in the existence of an external world because of the phenomena of constancy and coherence (T 1.4.2.18-43; SBN 194-210).1 Hume delineated these two aspects of our sensory experience, and claimed that they influence the imagination in such a way as to generate belief in the existence (...) of unperceived objects, independent of the mind. There is disagreement among philosophers as to the proper way to characterize constancy and coherence and the ways in which they respectively lead us to believe in external objects. The most straightforward account of coherence seems to make it the same as Hume's concept of causality. Yet Hume denies that they are the same ; and commentators disagree as to how to understand Hume's distinction between the two. As to constancy, many philosophers, following H.H. Price,2 have argued that it is really just a special case of coherence, and that its role in generating belief in external objects is the same as that of coherence. There is consequent puzzlement as to why Hume attributed a different, and more important, role to constancy. In an important recent book, Louis E. Loeb has proposed a very interesting two-part solution to this last puzzle: First, Hume is convinced that the commonsense view of the external world is patently false; so he cannot allow that it results from something as reasonable as causal inference. But the way coherence leads to belief in external objects is a form of causal inference. So, Hume wants constancy to lead to belief in external objects in a different, less reasonable way; and he wants constancy to be more important than coherence in leading to belief in the external world. Second, Hume did not realize that constancy is simply a special case of coherence (or causality), because of certain assumptions about causality that he Ira M. Schnall is at the Department of Philosophy, Bar-Ilan University, Ramat-Gan, Israel 52900. e-mail: [email protected] 34 Ira M. Schnall had inherited from his predecessors (i.e., he did not see the causality involved in the relation between an object's existing at one moment and its existing at a later moment). Therefore he appealed to non-rational mechanisms of the imagination to explain how constancy leads us to posit external objects.3 I will try to show that solutions such as Loeb's, which grant the affinity between coherence and causality and the reducibility of constancy to coherence, are unnecessary. I will propose a way to make sense of Hume's claim that coherence is not the same as causality; and I will argue that what Hume calls 'constancy' is not, and should not be, the same as, or reducible to, coherence. After introducing some basic terms, including 'constancy' and 'coherence' themselves (in section I), I will discuss the proper characterization of coherence and how it differs from causality (section II). Then I will discuss Hume's account of constancy and how it leads to belief in external obj ects; and I will contrast it with the alternative account, referred to above, that is widely held to be preferable (section III). I will argue that Hume's own account has certain advantages over the alternative (section IV) and that the main arguments against Hume's account are inconclusive (sections V and VI). The argument of section IV will yield an explanation of Hume's assigning more importance to constancy than to coherence. Finally, I will suggest (in the concluding section) that though Hume considered constancy and coherence to be merely the psychological "causes" that "induce us to believe in the existence of body," we can use them as a basis of an epistemological justification of our belief in the external world. I will make extensive use of H. H. Price's Hume's Theory of the External World; for much of the current understanding, as well as misunderstanding, of Hume's concepts of constancy and coherence is the result of the detailed analyses and arguments in that work.4 I First of... (shrink)

1. Readers of Hume, even those who call attention to the depth and variety of his skeptical excursions, now happily admit that Hume is, in crucial respects, a “naturalist.” A naturalist is, broadly, someone who emphasizes the natural sources of our beliefs, attitudes, and practices; and Hume surely is at least this kind of naturalist. But understanding Hume’s naturalism to include only this general explanatory commitment obscures as much as it reveals, I will argue, about the text of Treatise I (...) iv, where Hume examines various skeptical “systems of philosophy.” To understand that part of the Treatise, we must, I will argue, understand Hume’s shifting allegiances to different kinds of naturalism. (shrink)

The use of Buddhist teachings and practices in psychotherapy, once described as a new, popular trend, should now be considered an established feature of the mental health field in the United States and beyond. Religious studies scholars increasingly attend to these activities. Some express concern about what they view as the secularizing medicalization of centuries old traditions. Others counter with historical precedent for these phenomena comparing them to previous instances when Buddhist teachings and practices were introduced into new communities for (...) healing benefit like medieval China. I reveal that a growing number of clinicians also describe their activities in comparison to moments of Buddhist transmission like medieval China. Drawing on the models of scholars like Robert Ford Campany and Pierce Salguero, I outline the possible benefits and limits of such comparisons. I ultimately conclude that scholars use comparison to normalize these contemporary phenomena as cohering to a historical pattern and their interpretations are subsequently employed by clinicians to legitimate their activities. (shrink)