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)

While rooted in careful study of Mead’s original writings and transcribed lectures and the historical context in which that work was carried out, the papers in this volume have brought Mead’s work to bear on contemporary issues in metaphysics, epistemology, cognitive science, and social and political philosophy.

Abstract An argument originated by Brandon Carter presents humankind's imminent extinction as likelier than we should otherwise have judged. We ought to be reluctant to think ourselves among the earliest 0.01 %, for instance, of all humans who will ever have lived; yet we should be in that tiny group if the human race survived long, even at just its present size. While such reasoning attracts many criticisms, perhaps the only grave one is that indeterminism means there is not yet (...) any firm, theoretically predictable fact of how long the human race will survive. This, though, might not save Everett's many?worlds theory from a variant on Carter's point. Everett seemingly pictures observers as splitting into ever more versions, which explains away all apparent indeterminism; but then, absurdly, all except a vanishingly tiny proportion of one's versions would come into existence near one's death, outweighing all apparent evidence that death was not imminent. The need to avoid such a result severely constrains Everett?type theories. We need theories in which observer?versions diverge without increasing their numbers in any straightforward way. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Ethics & the Environment 7.1 (2002) 147-153 [Access article in PDF] Book Review Rattling the Cage: Toward Legal Rights for Animals Rattling the Cage: Toward Legal Rights for Animals Steven M. Wise. Foreward by Jane Goodall. Cambridge, Mass.: Perseus Books, 2000. pp. 384. US $17.50. ISBN 0-7382-0437-4 (Paperback) "Ancient philosophers claimed that all nonhuman animals had been designed and placed on this earth just for human beings. Ancient jurists (...) declared that law had been created just for human beings. Although philosophy and science have long since recanted, the law has not." Steven M. Wise, Rattling the Cage, p. 4. Readers of this journal are well-versed in the myriad ways in which nonhuman animals are harmfully exploited at the hands of human beings—from battery hens and veal calves to mass-produced pigs; from Pennsylvania pigeon shoots to canned hunts on Texas ranches; from rodeos to roadside zoos; from LD-50 toxicity tests on rats and Draize eye tests on rabbits to head trauma and infectious disease experimentation on primates. Despite other sticking points, it is by now uncontroversial among [End Page 147] nonanthropocentric theorists that, in utilitarian terms, the benefits to humans of the above practices fall far short of justifying the harms they cause to their nonhuman victims or, in deontological terms, that they violate the rights of creatures with inherent value. Indeed, these arguments are so well-rehearsed and so widely regarded as compelling that it no longer seems particularly bold to predict that if reason ever prevails over tradition and prejudice, the future will look back on this generation's treatment of our fellow creatures with the same kind of shame and condemnation with which European Americans regard our slaveholding past.More sobering but equally familiar is the observation that decisive arguments for the gross immorality of existing practices will bring about neither their elimination nor significant reform as long as the presumed legitimacy of human exploitation of nonhuman beings remains entrenched in both popular consciousness and economic, political, and legal institutions. In the interests of chipping away at popular apathy, academics should no doubt go on repeating the well-worn arguments against speciesism in classrooms, popular venues, and professional research. But in a world structured far more directly by the interests of a powerful few than by the values of the many, this consciousness-raising strategy properly plays at most a supporting role to the even more vital project of challenging and ultimately restructuring the institutions that sanction and carry out these injustices. In short, what nonhuman animals need from ethically sensitive intellectuals is not just rational argument, but effective legal and political action.One of the main institutional obstacles to progress in this area is undoubtedly the legal relegation of animals to property status—which is why Steve M. Wise's Rattling the Cage: Toward Legal Rights for Animals is such an important book. Wise teaches animal rights law at Harvard, Vermont, and John Marshall Law Schools and has spent more than twenty years fighting for animals in the legal system; his book displays the bittersweet fruit of that experience. The tenor throughout is a mixture of conviction in the justice of his cause—which cannot but sustain a vision of its eventual success—together with the frustration and determined patience borne from decades of butting up against an utterly implacable wall. An eloquent foreword by Jane Goodall, together with Wise's own harrowing first chapter, describe the nightmarish existences imposed on our nearest nonhuman relatives, the chimpanzees and bonobos, for the sake of science, entertainment, and profit—nightmares enabled by a legal system that [End Page 148] treats all nonhumans as mere things. An engaging storyteller with a synthetic conception of the history of ideas, Wise unearths the origins of this conception of animals in the Great Chain of Being, demonstrates its defeat by Darwinian science, and builds piece by piece a case—drawing heavily on research into animal consciousness—for extending legal rights at least to chimpanzees and bonobos.The substantive theses of this case are, first, that the denial of... (shrink)

John Bowlby's use of evolutionary theory as a cornerstone of his attachment theory was innovative in its day and remains useful. Del Giudice's target article extends Belsky et al.'s and Chisholm's efforts to integrate attachment theory with more current thinking about evolution, ecology, and neuroscience. His analysis would be strengthened by (1) using computer simulation to clarify and simulate the effects of early environmental stress, (2) incorporating information about non-stress related sources of individual differences, (3) considering the possibility of (...) adaptive behavior without specific evolutionary adaptations, and (4) considering whether the attachment construct is critical to his analysis. (shrink)

Alternate View Column AV-48 Keywords: nonlinear quantum mechanics FTL communication other universes Everett Wheeler Published in the October-1991 issue of Analog Science Fiction & Fact Magazine ; This column was written and submitted 3/10/91 and is copyrighted ©1991 by John G. Cramer. All rights reserved. No part may be reproduced in any form without the explicit permission of the author.

The interpretation of quantum mechanics due to Everett (1957) postulates the existence of many worlds. The analysis of modality due to Lewis (1986) is supported.

In March 1928, John Dewey responded to a request from Marie Meloney, editor of the New York Herald-Tribune Sunday Magazine, and offered his recommendations on recently published texts on education. Dewey wrote, "I think the best educational books of recent publication are Bode, Modern Educational Theories . . . Kilpatrick, Education for a Changing Civilization . . . & Martin, The Meaning of a Liberal Education".1 This was not the first time Dewey recommended Everett Dean Martin's book. In (...) 1927, the editors of the Journal of the National Education Association approached Dewey and asked, "What book have you recently found especially worthwhile? Something that you have read easily, eagerly, and with profit—either in .. (shrink)

Bas van Fraassen advocates a “Copenhagen variant” of the modal interpretation of quantum mechanics. However, he believes that the Copenhagen approach to measurement is not fully satisfactory, since it seems to rule out the possibility of providing a physical account of the observation process. This was also what John Wheeler had in mind when, in the mid-1950’s, he sponsored the “relative state” formulation proposed by his student Hugh Everett. Wheeler, who considered himself an orthodox Bohrian, tried to convince (...) Bohr to accept the improvement of the Copenhagen approach represented in his eyes by Everett’s proposal. This attempt gave rise to a lively debate, which has been only recently documented, and which provides an interesting framework for the appraisal of van Fraassen’s own programme. (shrink)

Hugh Everett’s “Universal Wave Theory Formulation of Quantum Mechanics”, though endorsed and promoted by his mentor John Wheeler, was dismissed by the mainstream in quantum mechanics. Why was it sidelined by those who endorsed the Copenhagen interpretation and John von Neumann’s approach to the famous measurement problem? Everett’s theory was taken up later by Bryce DeWitt under an interpretation, the many worlds universe theory, that is not actually how Everett interpreted his own formulation. I argue (...) that by looking at science as a social institution according to Ian C. Jarvie’s critique of Karl Popper’s view of science as a “Republic,” we can see how Everett was sidelined: external pressures of the Cold War and McCarthy and internal pressures of Big Science and the “military-industrial complex.”. (shrink)

Peter Byrne tells the story of Hugh Everett III (1930-1982), whose "many worlds" theory of multiple universes has had a profound impact on physics and philosophy. Using Everett's unpublished papers (recently discovered in his son's basement) and dozens of interviews with his friends, colleagues, and surviving family members, Byrne paints, for the general reader, a detailed portrait of the genius who invented an astonishing way of describing our complex universe from the inside. Everett's mathematical model (called the (...) "universal wave function") treats all possible events as "equally real", and concludes that countless copies of every person and thing exist in all possible configurations spread over an infinity of universes: many worlds. Afflicted by depression and addictions, Everett strove to bring rational order to the professional realms in which he played historically significant roles. In addition to his famous interpretation of quantum mechanics, Everett wrote a classic paper in game theory; created computer algorithms that revolutionized military operations research; and performed pioneering work in artificial intelligence for top secret government projects. He wrote the original software for targeting cities in a nuclear hot war; and he was one of the first scientists to recognize the danger of nuclear winter. As a Cold Warrior, he designed logical systems that modeled "rational" human and machine behaviors, and yet he was largely oblivious to the emotional damage his irrational personal behavior inflicted upon his family, lovers, and business partners. He died young, but left behind a fascinating record of his life, including correspondence with such philosophically inclined physicists as Niels Bohr, Norbert Wiener, and John Wheeler. These remarkable letters illuminate the long and often bitter struggle to explain the paradox of measurement at the heart of quantum physics. In recent years, Everett's solution to this mysterious problem - the existence of a universe of universes - has gained considerable traction in scientific circles, not as science fiction, but as an explanation of physical reality. (shrink)

It is usually held that the standard collapse model of a quantum measurement process grounds a kind of fundamental time asymmetry. The question whether and how it should be possible to reconstruct uniquely one's own history in an Everett no-collapse interpretation of quantum theory is investigated. A particular approach to the Everett interpretation, due to John S. Bell, is considered, according to which one of the chief claims of the Everett quantum theory is precisely that it (...) allows us to do without the notion of history. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Remixing the Classroom: Toward an Open Philosophy of Music Education by Randall Everett AllsupJuliet HessRandall Everett Allsup, Remixing the Classroom: Toward an Open Philosophy of Music Education (Bloomington, IN: Indiana University Press, 2016).As a leading voice in music education, Randall Allsup works continually to reconceptualize music education toward democratic and socially just praxis.1 He routinely challenges the field to become self-conscious of practices that limit forward (...) movement, providing powerful critiques2 and urging music education toward open possibilities.3 Remixing the Classroom: Toward an Open Philosophy of Music Education is work that will shift our field. His comprehensive philosophy of music education looks, longs, for moral openings4 through which twenty-first-century music education may become a space of possibility. His writing interweaves stories and theory toward what he calls an "open philosophy," drawing upon the ideas of John Dewey, Maxine Greene, and Roland Barthes. Allsup introduces stories of Dapper Dan, Jiro Ono, Kafka, Atul Gawande, and the Orpheus Orchestra in New York City to illustrate powerful points about current and possible paradigms of music education.Chapter 1, "Toward Open Encounters," discusses the making and breaking of the law (tradition) and explores how tradition and the Master-Apprentice model restrict what is possible in music education. Allsup explores the nature of music education and the limitations it places upon its participants. Chapter 2, "Music-Teacher Quality and Expertise," asks fundamental questions of our field and [End Page 100] explores and challenges the "place and purpose of public schooling in a democratic society."5 Allsup speaks to the function of education and critiques music education. Chapter 3, "learning in laboratories," puts forward a Deweyan laboratory model in which a museum is at the center of the school with learning laboratories situated around it. He explores what this structural fluidity might enable and develops notions of lawmaking and lawbreaking, extending possibilities of the open encounter. The final chapter, "looking, Longing, for Moral Openings," calls on music educators to embrace a more open music education paradigm. Allsup draws upon Greene to challenge music education to move "from the predictable to the possible."6 He puts forward the Orpheus Orchestra, a conductorless orchestra, as one possibility.I situate myself as an anti-racist, anti-colonial, feminist scholar rooted in anti-oppression scholarship.7 locating my review through this framework, I elaborate upon what I see as the major strengths and limitations of this work, drawing upon Judith Butler8 and postcolonial theory. significantly, Allsup's book calls upon music education to "give an account of [it]self" and promotes a self-consciousness crucial for our field in the age of high stakes accountability measures. I contend that he provides a music education philosophy for what stuart Hall terms the "postcolonial moment"9 and ultimately positions music education as a space of possibility. Alongside these strengths, I offer a challenge toward what I view as the open possibilities of closed forms and a critique of his "pedagogy of travel and surprise."Judith Butler points to the impossibility of giving an account of oneself. she notes,I speak as an 'I,' but do not make the mistake of thinking that I know precisely all that I am doing when I speak in that way. I find that my very formation implicates the other and me, that my own foreignness to myself is, paradoxically, the source of my ethical connection with others.10Butler notes the subject's "partial opacity to [her]self."11 In Remixing the Classroom, Allsup calls upon music educators to account for the practices and traditions continually reinscribed in the field. He poses challenging but fundamental questions in the work in music education, asking readers to consider what they do unconsciously. Butler asserts we can never fully account for ourselves. Allsup challenges the field to try, pushing music educators to face hard truths and limitations of what music education is and has been. In chapter 1, for example, he argues:To call a studying musician "unmusical" is to extinguish a light; it is to act as if the future is certain and that human potential is somehow fixed. It is to act [End Page 101... (shrink)

Hugh Everett III died of a heart attack in July 1982 at the age of 51. Almost 26 years later, a New York Times obituary for his PhD advisor, John Wheeler, mentioned him and Richard Feynman as Wheeler’s most prominent students. Everett’s PhD thesis on the relative state formulation of quantum mechanics, later known as the “Many Worlds Interpretation”, was published (in its edited form) in 1957, and later (in its original, unedited form) in 1973, and since (...) then has given rise to one of the most radical schools of thought in the foundations of quantum theory. Several years ago two conferences held in Oxford and in the Perimeter Institute celebrated the occasion of 50 years to the first publication of Everett’s thesis. The book Many worlds? grew out from contributions to these conferences, but, as its editors emphasize, it is more than mere conference proceedings. Instead, an attempt was made to assemble an impressive collection of papers which together illustrate the promise of the many worlds interpretation and the obstacles it faces. 23 papers divided into six sections follow an introduction by Simon Saunders, one of Oxford’s fiercest Everettians. The first four sections cover two thorny issues that have been flagged by contemporary opponents to the many worlds interpretation, namely, the problem of ontology and the problem of probability, while the fifth discusses alternatives to Everett such as Bohmian mechanics and information–theoretic approaches to quantum theory. The sixth section seems to be a wild card, hosting several papers unrelated to each other, including one of the most interesting contributions to this volume on the history of Everett’s thesis and his (some may say all too) short academic career. Each section concludes with transcripts of the discussion session that took place after the talks, thus giving an additional emphasis to the points of contention. Apart from general comments on the volume, in what follows I would like to concentrate on few papers I found especially illuminating. Start with ontology.. (shrink)

For the sake of clarity and brevity, this chapter uses binary language as regards gender. Chrisjen Avasarala's team is shoving her back into the modern equivalent of the role Aristotle established for women. Aristotle tried to explain why women could not be good politicians. Women were in a subservient position because, at least according to Aristotle, they were, rare to medium. Men were well done, which meant that the “courage of men lies in commanding, a woman's lies in obeying.” Surely (...) the women of the Romantic Era, immortalized so strikingly in paintings such as Frederic Leighton's Flaming June, Edmund Blair Leighton's The Accolade, and Sir John Everett Millais’ Ophelia. At a couple of points, Romantic‐Era philosophy intersects with Avasarala's treatment in The Expanse. (shrink)

Like John Skrentny, Paul Gottfried sees in the Civil Rights Act of 1964 the seeds of Affirmative Action, racial and gender asides, quotas, goals and timetables. He contends that this was “the likely way that the Act would be interpreted.” But an act written in part in the office of Republican Senator Everett Dirksen and amended by the conservative Texas Republican John Tower was not necessarily, nor even likely, to be converted into the AA commissariat machine. Because (...) it turned out that way, does not mean this was the only, or even the probable, outcome. There was a dire need for the Civil Rights Act of 1964 because employers, particularly in the South, refused to hire blacks even when they were better qualified than whites. (shrink)

This chapter contains section titled: General Remarks What Utilitarianism Is Of the Ultimate Sanction of the Principle of Utility Of What Sort of Proof the Principle of Utility is Susceptible On the Connexion Between Justice and Utility.

In general we think of reasoning as a way of moving from some body of evidence to a belief that is drawn as a conclusion from it. But is it possible for reasoning to conclude in action, i.e., in a person’s intentionally doing one thing or another? In PRACTICAL SHAPE Jonathan Dancy answers 'Yes', on the grounds that "when an agent deliberates well and then acts accordingly, the action done is of the sort most favoured by the considerations rehearsed, taken (...) as a whole—just as when an agent reasons well and then believes accordingly, the belief formed ... is of the sort most favoured by the considerations rehearsed, again taken as a whole" (Dancy 2018, p. 29). I critique this supposed parallelism between reasoning to action and reasoning to belief, arguing in two ways that in practical reasoning the action that is one’s conclusion need not be meant to be, or to be of a sort, that is most favored by the considerations that one reasons from. I then go on to explain why this should be: that in practical reasoning the correct conclusion to draw is not supposed to have been determined in advance, because this is a form of reasoning by which we create truth through acting rather than reflecting a truth that is independently so. (shrink)