Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. We present interactive heatmaps that allow comparison of distributions of integration sites to (...) genomic features and that support numerous user-defined statistical tests. To summarize integration site data from human gene therapy samples, we developed a reproducible report format that catalogs sample population structure, longitudinal dynamics, and integration frequency near cancer-associated genes. We also introduce a novel summary statistic, the UC50, which provides a single number summarizing possible clonal expansion. Using these tools, we characterize ongoing longitudinal characterization of a patient from the first trial to treat severe combined immunodeficiency-X1, showing successful reconstitution for 15 years accompanied by persistence of a cell clone with an integration site near the cancer-associated gene CCND2. Software is available at https://github.com/BushmanLab/INSPIIRED. (shrink)

This chapter contains sections titled: Sartre's Life Early Phenomenological Works Phenomenological Ontology: Being and Nothingness Phenomenological Marxism Conclusion.

In lieu of an abstract, here is a brief excerpt of the content:Camus’s Meursault and Sartrian IrresponsibilityDavid ShermanIn the wake of poststructuralism, with its glorification of the libidinal play of unaccountable, fragmented subjectivities, the concept of personal responsibility has been rehabilitated. From the French fascination with various forms of neo-Kantianism to the American interest in homey (albeit demagogic) books on the virtues, personal responsibility is regaining currency. But what, exactly, does it mean to be personally responsible? When Albert Camus suggested (...) in “Neither Victims Nor Executioners” that non-violence was the “responsible” position for intellectuals to take on the Algerian crisis, he was reproached for legalistically evading responsibility by his erstwhile friend Jean-Paul Sartre. Sartre, who offered up the concept of “absolute responsibility,” and viewed any attempt to obscure the nature of this ontological burden for oneself as “bad faith,” regarded Camus’s position as just such an attempt: “If you’re not victims when the government which you voted for, when the army in which your younger brothers are serving... have undertaken race murder, you are, without a shadow of a doubt, executioners.” 1 For Sartre, who tentatively advocated revolutionary violence, taking responsibility meant acknowledging that “bloodying one’s hands” is unavoidable.The concept of personal responsibility is well considered within the context of French existentialism, which made it one of its hallmarks. In this essay, however, I shall approach personal responsibility from the vantage point of its opposite, personal irresponsibility. Towards this end, I shall consider Meursault, the protagonist in Camus’s The Stranger, whom I take to be one of the most irresponsible characters in literature. The depths of Meursault’s irresponsibility can best be appreciated, fittingly enough, within Sartre’s psychoanalytic framework. [End Page 60]IIn Being and Nothingness, Sartre offers up the ontologically rooted phenomenon of bad faith, which, for present purposes, can be explicated as follows: consciousness, which is intentional (nothing more than that which it is conscious of), reflectively reconstitutes the Self, which does not exist in consciousness but as an object in the external world. There is no intrinsic Self, and the Self that does exist is perpetually being transcended. Despite this state of unremitting transcendence, however, at any point in time there are the undeniable facts of our particular existences, which (however we choose to interpret them) define the range of our possible projects. These brute facts, which are inexorable, constitute our facticity. Thus, Sartre tells us, there is a “double property of the human being, who is at once a facticity and a transcendence” (B&N, p. 98). 2 It is in a person’s approach to the relationship between these two properties, which is marked by an irresolvable tension, that bad faith arises: “Bad faith does not wish either to coordinate them or to surmount them in a synthesis. Bad faith seeks to affirm their identity while preserving their differences. It must affirm facticity as being transcendence and transcendence as being facticity, in such a way that at the instant when a person apprehends the one, he can find himself abruptly faced with the other” (B&N, p. 98).Sartre provides numerous illustrations of individuals who flee from either their facticity or transcendence. For example, there is the homosexual and his interlocutor, the “champion of sincerity.” The former, despite repeated homosexual encounters, refuses to draw the conclusion that he is a homosexual; instead, he sees both his past behavior and his present inclinations as part of a “restless search.” Conversely, the latter demands that the homosexual sincerely avow what he is, “a homosexual.” Both are in bad faith. The homosexual denies responsibility for all that he has done by perpetually pushing his conception of Self into the future, and thus perpetually beyond the reach of his ability to make judgments about himself—he makes a mockery of his past and present choices. The champion of sincerity, on the other hand, pushes the homosexual’s conception of Self into the past in order to make it a thing—he denies the homosexual’s (and perhaps his own) freedom to make future choices, which is what enables us to transcend what we presently are. The former flees facticity; the latter, transcendence.All persons in bad faith fall... (shrink)

Paul Weiss continues the brilliant analysis of art he began in _The World of Art _and _Nine Basic Arts_—here_ _in the medium of film, at which he takes a close and inde­pendent look. Writing in a vigorous, jargon-free style, and covering all aspects of films and film making, Mr. Weiss presents a fresh, new approach to the study of our newest art. During the course of writing _Cinematics_,_ _Mr. Weiss asked various writers, critics, scholars, and producers long involved with (...) film to read and remark on what he had written. Five of them—Eric Sherman, Joseph Williman, Arthur Knight, David Slavitt, and Robert Thom—provided comments which are incorporated in the text. Their remarks are often trenchant, and perceptively provocative. These men frequently comment on lines of inquiry suggested in the book and often take issue with what has been said. The result is a kind of dialogue crisscrossed with stimu­lating insights. While this book is aimed at the general reader, Mr. Weiss hopes that experts and practitioners of film making will benefit from this fresh, independent, and philo­sophically based inquiry. Readers already familiar with Mr. Weiss’s writings will delight in this distillation of his thought on an art so intimately a part of our cul­ture. (shrink)

This useful, introductory guide to Continental philosophy is another fine volume within the Blackwell Philosophy Guides series, whose editor is Steven M. Cahn. Robert Solomon teaches business and philosophy at the University of Texas at Austin, and David Sherman teaches philosophy at the University of Montana–Missoula.

Most traditional accounts of Aristotle's theory of ethical education neglect its cognitive aspects. This book asserts that, in Aristotle's view, excellence of character comprises both the sentiments and practical reason. Sherman focuses particularly on four aspects of practical reason as they relate to character: moral perception, choicemaking, collaboration, and the development of those capacities in moral education. Throughout the book, she is sensitive to contemporary moral debates, and indicates the extent to which Aristotle's account of practical reason provides an (...) alternative to theories of impartial reason. (shrink)

This edition includes a new introduction by Peter J. Gomes that reflects on the impact of this book in the years since it was written.

Focusing on the logistics of perception, this title introduces the author's understanding of 'picnolepsy' - the epileptic state of consciousness produced by speed, or rather, the consciousness invented by the subject through its very absence: the gaps, glitches, and speed bumps lacing through and defining it.

Paul Thom's book presents Kilwardby's science of logic as a body of demonstrative knowledge about inferences and their validity, about the semantics of non-modal and modal propositions, and about the logic of genus and species. This science is thoroughly intensional. It grounds the logic of inference on "that in virtue of which" the inference holds. It bases the truth conditions of propositions on relations between conceptual entities. It explains the logic of genus and species through the notion of essence. (...) Thom interprets this science as a formal logic of intensions with its own proof theory and semantics. This comprehensive reconstruction of Kilwardby's logic shows the medieval master to be one of the most interesting logicians of the thirteenth century. (shrink)

In the modern day, it is understood that the role of the teacher comprises aspects of therapy directed towards the child. But to what extent should this relationship be developed, and what are its concomitant responsibilities? This book offers a challenging philosophical approach to the inherent problems and tensions involved with these issues.

Even among scholars who emphasize Nietzsche’s naturalism (“the naturalists”), what it actually involves is disputed. This article identifies the foundations of Nietzsche’s naturalism and then elaborates on these foundations through a critical analysis of the works of those naturalists who also identify them. Nietzsche is a methodological naturalist, who, epistemically, is a reliabilist, and while he acknowledges the innate limitations of our cognitive inheritance, which is reflected in his perspectivism, he sees no reason to conclude that we cannot grasp the (...) natural world truly. As to the primary issue in scientific explanation, causation, Nietzsche adopts a regularity theory as early as The Gay Science, and, on the basis of this theory, rejects determinism. One consequence of this analysis is that Nietzsche’s naturalism is not as restrictive as the naturalists tend to portray it, and this opens up new possibilities for interpreting many of his other commitments. (shrink)

Foreword William Schweiker Paul Tillich, one of the great Protestant theologians of the twentieth century, addresses in Morality and Beyond a basic problem ...

“One day the day will come when the day will not come.” Bleak, but passionately political in its analysis of the social destruction wrought by modern technologies of communication and surveillance, Open Sky is Paul Virilio's most far-reaching and radical book. Deepening and extending his earlier work, he explores the growing danger of what he calls a “generalized accident,” provoked by the breakdown of our collective and individual relation to time, space and movement in the context of global electronic (...) media. But this is not merely a lucid and disturbing lament for the loss of real geographical spaces, distance, intimacy or democracy. Open Sky is also a call for revolt—against the insidious and accelerating manipulation of perception by the electronic media and repressive political power, against the tyranny of “real time,” and against the infantilism of cyberhype. Virilio makes a powerful case for a new ethics of perception, and a new ecology, one which will not only strive to protect the natural world from pollution and destruction, but will also combat the devastation of urban communities by proliferating technologies of control and virtuality. (shrink)

The first full-length study of Robert Kilwardby's commentary on Aristotle's Prior Analytics, based on a study of the medieval manuscripts.

[Significantly updated in Chapter 6 of Awareness and the Substructure of Knowledge] In order for a reason to justify an action or attitude it must be one that is possessed by an agent. Knowledge-centric views of possession ground our possession of reasons, at least partially, either in our knowledge of them or in our being in a position to know them. On virtually all accounts, knowing P is some kind of non-accidental true belief that P. This entails that knowing P (...) is a kind of non-accidental true representation that P. I outline a novel theory of the epistemic requirement on possession in terms of this more general state of non-accidental true representation. It is just as well placed to explain the motivations behind knowledge-centric views of possession, and it is also better placed to explain the extent of the reasons we possess in certain cases of deductive belief-updates and cases involving environmental luck. I conclude with three reflections. First, I indicate how my arguments generate a dilemma for Errol Lord’s view that possessing reasons is just a matter of being in a position to manifest one’s knowledge how to use them. Second, I explain how my view can simultaneously manage cases of environmental luck without falling prey to lottery cases. Finally, I sketch the direction for a further range of counterexamples to knowledge-centric theories of possession. (shrink)

The task of this chapter is to investigate and assess Grossmann’s view of the ontological status of categories. It has two dimensions. Because Grossmann does not offer a full discussion of the ontology of categories, we first need to present an interpretation of his view. Our point of departure is Grossmann’s claim that a category is a fundamental property of being (which implies that he holds view 3 above). Our second task is to assess the adequacy of his view. We (...) do this by raising some problems with Grossmann’s account, offering as an alternative view a version of 4 above, and defending it against what we construe as Grossmann’s possible counter-arguments. We argue that the best way to view categories themselves is as ontologically neutral insofar as this opens the way for particular categories to be linguistic entities, mental acts, or properties of extra-mental things. This requires, in turn, a qualified defense of two views rejected by Grossmann—common natures and modes of being. (shrink)

Conservatism about perceptual justification tells us that we cannot have perceptual justification to believe p unless we also have justification to believe that perceptual experiences are reliable. There are many ways to maintain this thesis, ways that have not been sufficiently appreciated. Most of these ways lead to at least one of two problems. The first is an over-intellectualization problem, whereas the second problem concerns the satisfaction of the epistemic basing requirement on justified belief. I argue that there is at (...) least one Conservative view that survives both difficulties, a view which has the further ability to undercut a crucial consideration that has supported Dogmatist views about perceptual justification. The final section explores a tension between Conservatism and the prospects of having a completely general account of propositional justification. Ironically, the problem is that Conservatives seem committed to making the acquisition of propositional justification too easy. My partial defense of Conservatism concludes by suggesting possible solutions to this problem. (shrink)

The Equal Weight View holds that, when we discover we disagree with an epistemic peer, we should give our peer’s judgment as much weight as our own. But how should we respond when we cannot tell whether those who disagree with us are our epistemic peers? I argue for a position I will call the Earn-a-Spine View. According to this view, parties to a disagreement can remain confdent, at least in some situations, by fnding justifable reasons to think their opponents (...) are less credible than themselves, even if those reasons are justifable only because they lack information about their opponents. (shrink)

Journal Name: Cognitive Linguistics Issue: Ahead of print.

Aristotle's modal syllogistic has been an object of study ever since the time of Theophrastus; but these studies have been somewhat desultory. Remarkably, in the 1990s several new lines of research have appeared, with series of original publications by Fred Johnson, Richard Patterson and Ulrich Nortmann. Johnson presented for the first time a formal semantics adequate to a de re reading of the apodeictic syllogistic; this was based on a simple intuition linking the modal syllogistic to Aristotelian metaphysics. Nortmann developed (...) an ingenious de dicto analysis. Patterson articulated the links between the modal syllogistic and the metaphysics, using an analysis which strictly speaking is neither de re nor de dicto. My own studies in this field date from 1976, when my colleague Peter Roeper and I jointly wrote a paper "Aristotle's apodeictic syllogisms" for the XXIInd History of Logic Conference in Krakow. This paper contained the disjunctive reading of particular affirmative apodeictic propositions, which I still favour. Nonetheless, I did not consider that paper's results decisive or comprehensive enough to publish, and my 1981 book The Syllogism contained no treatment of the modal syllogism. The paper's ideas lay dormant till 1989, when I read Johnson's and Patterson's initial articles. I began publishing on the topic in 1991. Gradually my thoughts acquired a certain comprehensiveness and systematicity, till in 1993 I was able to take a semester's sabbatical to write up a draft of this book. (shrink)

Le philosophe, collègue et ami de Michel Foucault, fait le portrait de ce dernier et présente les grands thèmes de sa pensée philosophique et politique.