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.

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.

Descartes is widely portrayed as the arch proponent of “the epistemological transparency of thought” (or simply, “Transparency”). The most promising version of this view—Transparency-through-Introspection—says that introspecting (i.e., inwardly attending to) a thought guarantees certain knowledge of that thought. But Descartes rejects this view and provides numerous counterexamples to it. I argue that, instead, Descartes’s theory of self-knowledge is just an application of his general theory of knowledge. According to his general theory, certain knowledge is acquired only through clear and distinct (...) intellection. Thus, in his view, certain knowledge of one’s thoughts is acquired only through clear and distinct intellection of one’s thoughts. Introspection is a form of intellection and it can be clear and distinct. Ordinarily, however, introspection isn’t clear and distinct but is instead confused with dubitable perceptions of bodies. To make introspection clear and distinct, we need to “sharply separate” it from all perceptions of bodies by doubting all perceptions of bodies. Without such radical doubt, introspection remains confused and we lack certain knowledge not just of the specific features of our thoughts, but even of the minimal claim that a thought exists. Far from being the high priest of Transparency, Descartes is radically opposed to it. (shrink)

In _Matter and Consciousness_, Paul Churchland presents a concise and contemporary overview of the philosophical issues surrounding the mind and explains the main theories and philosophical positions that have been proposed to solve them. Making the case for the relevance of theoretical and experimental results in neuroscience, cognitive science, and artificial intelligence for the philosophy of mind, Churchland reviews current developments in the cognitive sciences and offers a clear and accessible account of the connections to philosophy of mind. For (...) this third edition, the text has been updated and revised throughout. The changes range from references to the iPhone's "Siri" to expanded discussions of the work of such contemporary philosophers as David Chalmers, John Searle, and Thomas Nagel. Churchland describes new research in evolution, genetics, and visual neuroscience, among other areas, arguing that the philosophical significance of these new findings lies in the support they tend to give to the reductive and eliminative versions of materialism. Matter and Consciousness, written by the most distinguished theorist and commentator in the field, offers an authoritative summary and sourcebook for issues in philosophy of mind. It is suitable for use as an introductory undergraduate text. (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 confident, at least in some situations, by finding justifiable reasons to think their opponents (...) are less credible than themselves, even if those reasons are justifiable only because they lack information about their opponents. (shrink)

Upheavals of Thought is Martha Nussbaum’s most recent, sweeping and masterful study of the human life lived through the emotions. The book’s scope is expansive by any measurement, covering in the first part an historical and contemporary analysis of emotions, their sociality, developmental features, and cultivation; and in the second and third parts an in depth analysis of the specific emotions of compassion and love respectively, with chapter length discussions on love that take up Augustine, Dante, Mahler, Brontë, Whitman, Joyce (...) among others, and discussions on compassion that move through ancient philosophical and literary authors to contemporary discussions of justice and the construction of adequate measurements of the quality of life. (shrink)

This book demonstrates how children's imagination makes a continuing contribution to their cognitive and emotional development.

While Aristotle in the Nicomachean Ethics does not provide a guide for action in the form of rules for a decision process as deontological or consequentialistethical theories purport to do, he does present a description of the virtuous agent and the virtues that this agent exercises in his choices of action. In this paper Iargue that Aristotle’s mature virtuous agent characteristically exercises the virtue of wisdom (sophia) as well as the practical virtues of character and intelligence in his choices of (...) action and that students of virtue (those sincerely interested in becoming virtuous by acting as the virtuous agent does) can derive certain action-guiding rules from a description of these three virtues and how they are exercised by the mature virtuous agent in any given choice of action. (shrink)

Sarah McGrath (2008; 2011) argues that, when it comes to our controversial moral views, we have no reason to think we are less likely to be in error than those who disagree with us. I refer to this position as the Moral Peer View (MPV). Under pressure from Nathan King (2011a; 2011b), McGrath admits that the Moral Peer View need not always have been true, though she maintains it is true now. Although King seems to think there should be current (...) counterexamples to the Moral Peer View, he holds back from actually proposing any. I argue that those of us who favor marriage equality and gender equality are currently in a position to reject the Moral Peer View with regard to these issues, and I propose conditions under which people can reasonably take their moral beliefs to be epistemically advantaged. King and McGrath agree that opponents of slavery like William Wilberforce could reasonably believe they enjoyed an epistemic advantage over proponents of slavery, and I suggest that proponents of marriage equality and gender equality might make similar claims. I propose that we can make additional claims to epistemic advantages if we believe that (1) almost everyone that considers the matter admits they are advantages, (2) those who disagree with use would admit they are advantages, and (3) we can give a plausible explanation as to why those that we think are epistemically disadvantaged have not noticed that they are disadvantaged. Finally, I argue that it reasonable to think our controversial beliefs are justified if we can find reasons to think our opponents are mistaken, and do not see similar reasons to think ourselves mistaken. This is a better policy than supposing we are just as prone to make mistakes as our opponents, as the latter is both less defensible in theory, and more likely to stifle intellectual progress. (shrink)

Signed languages employ finely articulated facial and head displays to express grammatical meanings such as mood and modality, complex propositions, information structure, assertions, content and yes/no questions, imperatives, and miratives. In this paper we examine two facial displays: an upper face display in which the eyebrows are pulled together called brow furrow, and a lower face display in which the corners of the mouth are turned down into a distinctive configuration that resembles a frown or upside-down U-shape. Our analysis employs (...) Cognitive Grammar, specifically the control cycle and its manifestation in effective control and epistemic control. Our claim is that effective and epistemic control are associated with embodied actions. Prototypical physical effective control requires effortful activity and the forceful exertion of energy and is commonly correlated with upper face activity, often called the “face of effort.” The lower face display has been shown to be associated with epistemic indetermination, uncertainty, doubt, obviousness, and skepticism. We demonstrate that the control cycle unifies the diverse grammatical functions expressed by each facial display within a language, and that they express similar functions across a wide range of signed languages. (shrink)

Ever since Max Weber started an argument about the role of Protestantism in jump-starting northern Europe's economic development, scholars have clashed over the influence of religion and culture on a society's economic prospects. Today, many wonder whether the "explosion" of Protestantism in Latin America will effect a similar wave of growth and democratization. In this book, Sherman compiles the results of her field study and national survey of 1000 rural Guatemalan households. She offers persuasive evidence that, in Guatemala and (...) throughout the region, religious world-views significantly influence economic life. Sherman explains how the change in attitude and behavior that accompanies conversion from animism to a Biblically orthodox world-view has improved the domestic welfare and economic status of many families. Further, she asserts that this new attitude, sympathetic to democratic-capitalism, has created a "moral cultural soil" in which freedom, personal empowerment, an enhanced status for women, and a desire to get ahead can be nurtured. (shrink)