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)

The Restoration settlement, the political backcloth to Aubrey's essay, proceeded in two stages. The first, in, saw the rehabilitation of the King and the ...

Are extremists (incels, neo-nazis, and the like) characteristically answerable for their moral and political convictions? Is it necessary to offer them reasoned arguments against their views, or is it instead appropriate to bypass that kind of engagement? Discussion of these questions has centered around the putative epistemic autonomy of extremists. The parties to this discussion have assumed that epistemic autonomy is solely (or at least primarily) a matter of epistemic independence, of believing based on epistemic reasons one has assessed for (...) oneself. Here, though, I make the case for shifting the terms of the debate. Epistemic independence is not sufficient to make one answerable for one’s beliefs. Epistemic autonomy, in the sense that matters for answerability, is also a matter of what I call epistemic receptivity. Extremists may be fiercely epistemic independent, but that commitment is characteristically paired with severe deficiencies in empathic orientation. Severe deficiencies in empathic orientation undermine extremists’ ability to adequately engage with competing evaluative perspectives, and thus compromise extremists’ epistemic autonomy. I consider how this conclusion should inform our thinking about what we owe to extremists. (shrink)

ABSTRACT:Must even Confucian rights skeptics—those who are, on account of their Confucian beliefs, skeptical of the existence of human rights, and believe that asserting or recognizing rights is morally wrong—concede that in the workplace, they are morally obligated to recognize rights? Alan Strudler has recently argued that such is the case. In this article, I argue that because Confucian rights skeptics locate wrongness in inconsistency with the idea of “Confucian community,” Confucian community should be viewed as a moral ideal. I (...) then argue that Confucian rights skeptics ought to act in a manner that is consistent with this ideal, even when the ideal has not yet been realized, just as Kantians ought to act consistently with the Kantian kingdom of ends ideal. Accordingly, contrary to Strudler, I argue that Confucian rights skeptics need not concede that they are morally obligated to recognize rights in the workplace. This conclusion suggests the need for inquiry into the metaphysical foundations of these conflicting views. However, such inquiry is commonly thought to lie beyond the scope of philosophical business ethics proper. I conclude the article by suggesting a number of reasons for business ethicists to consider rejecting the prevalent narrow conception of the scope of the discipline.In this discussion I explore challenges to a particular Confucian system of morality that generally eschews reliance on rights. I argue that such a system may at the same time both assert that there are moral problems with rights and assert that it is acceptable to invoke rights in limited contexts. Adam Bailey has objected that the position I defend is inconsistent. I answer Bailey’s objections. (shrink)

_Utilitarianism_ is a classic work of ethical theory, arguably the most persuasive and comprehensible presentation of this widely influential position. While he didn’t invent utilitarianism, John Stuart Mill offered its clearest expression and strongest defense, and he expanded the theory to account for the variety in quality that we find among pleasures and pains. The complete text of the 1871 edition is included, along with selections from Jeremy Bentham’s An Introduction to the Principles of Morals and Legislation. Andrew Bailey’s (...) detailed introduction examines the context of Mill’s writing and offers guidelines on how to read the text accurately and critically. The complete text of the 1871 edition of _Utilitarianism_ is presented here, with footnote annotations added to clarify unfamiliar references and terminology for the student reader. A detailed introduction by the editor is divided into brief digestible parts discussing the context of the text and offering guidelines on how to read it accurately and critically. This edition has its origin in the acclaimed _Broadview Anthology of Social and Political Thought_ and adheres to the anthology’s format and high standard of accuracy and accessibility. (shrink)

Philosophy and Hip-Hop: Ruminations on Postmodern Cultural Form opens up the philosophical life force that informs the construction of Hip-hop by turning the gaze of the philosopher upon those blind spots that exist within existing scholarship. Traditional Departments of Philosophy will find this book a solid companion in Contemporary Philosophy or Aesthetic Theory. Inside these pages is a project that parallels the themes of existential angst, corporate elitism, social consciousness, male privilege and masculinity. This book illustrates the abundance of philosophical (...) meaning in the textual and graphic elements of Hip-hop, and thus places Hip-hop within the philosophical canon. (shrink)

Author Aubrey Neal suggests that one of these issues that lingers with us today is scepticism, and in 'How Skeptics do Ethics', he unravels the thread of this philosophy from its origins in enlightenment thinking down to our present age.

In this paper we introduce a new property of families of functions on the Baire space, called pseudo-dominating, and apply the properties of these families to the study of cardinal characteristics of the continuum. We show that the minimum cardinality of a pseudo-dominating family is min{.

In lieu of an abstract, here is a brief excerpt of the content:A Painful Lack of ConnectionChristopher Bailey (bio)Keywordsdepression, detachment (as a defense), empathy, evolution, masculinityI greatly appreciate the incredibly thoughtful responses to my clinical anecdote, “A Painful Lack of Wounds.” There is, in some more than others, a peculiar aura of detachment that, for me, evokes the very abyss (and its lack of an opposing force) that Colin and I found ourselves staring into that day. I realize, of (...) course, that some level of detachment is necessary to allow airspace for intellectual arrivals and departures.Detachment, moreover, is a form of emotional and psychological escape. In contrast with physical escape, detachment makes something that is present seem absent and, in that regard, is more like camouflage than flight. In some of the responses, therefore, I find myself tuning out the intellectual labyrinth and tuning in to how well it obscures its creator. What wounds or weaknesses, I wonder, is the author trying to hide? Insulin-dependent diabetes? An inferiority complex? Cannot climb chain-link fences? Is he or she hiding these problems from him- or herself? Or just the rest of us?This drive to connect, to regain the biological and the personal, was the ultimate point of my anecdote. I am not suggesting that human beings are biologically built for warfare or that all forms of pathology, at one time, must have conferred some evolutionary advantage. But as omnivorous, social primates, we are definitely adapted for engagement (of all varieties).Certainly, we need to avoid overidentification or sweepingly premature conclusions. Still, no doctor would deny his or her nostrils if cued by a foul, fetid odor to examine a patient for bed sores or gangrene. Likewise, we cannot in our clinical efforts recoil from the same instincts for sniffing out pathology that once made us successful predators. To paraphrase Jeffrey Masson and Susan McCarthy, the authors of When Elephants Weep, when one feels, from observing a bear, that the bear is sad, chances are the bear is sad. To call this anthropomorphizing is a much less parsimonious explanation than the possibility that evolutionary cousins can accurately read one another. And if inter-mammalian empathy is not too much of a stretch, we can probably trust what we feel from an animal of our own species.Granted, it is a long way from feeling to formulation. I chose to write about Colin because he expressed a kind of craving I am finding in a lot of men these days. I do not doubt that cultural pressure, heaped on personal issues and genetic prerogatives, can push a man to place heroism at the center of his psychic universe. Nonetheless, I find it odd that ostensibly comprehensive formulations, like the biopsychosocial model, fail to acknowledge the greater ecosystem in which we dwell. The wheelchair-accessible communities we have created to detach from natural selection are [End Page 249] the same frictionless planes on which masculinity, like a grotesque evolutionary artifact, tends to stumble nowadays.In short, were we not so dependent on the very things we call progress, had we not atrophied from a well-adapted ape to one that can die of hypothermia in 50° weather, I doubt if Colin's insecurity (or anyone's) would be so great. Not that I did not challenge Colin on aspects of his self-doubt. But I did not see it as “inappropriate” either. And although I agree a sense of helplessness can be both cause and effect of depression, his self-doubt, to me, was more than just a “cognitive error” unconsciously conceived as cover for a dark mood. Nondepressed people, after all, score higher than their depressed counterparts on measures of self-deception. The same false sense of security that we, as a culture, have coasted on for decades was shattered for Colin in Iraq. And I believe that is a good thing.Related ArticlesFeature Article: Clinical Anecdotes: A Painful Lack of WoundsCommentary: The Nature of Proof in PsychiatryCommentary: Truth and Healing a Veteran's DepressionCommentary: Inappropriate RegretCommentary: The Cultural Context of Post-traumatic Stress DisorderCommentary: Explication or Explanation?Commentary: The Importance of What Psychiatrists Care AboutCommentary: Mourning or MelancholiaResponse: A... (shrink)

Must even Confucian rights skeptics—those who are, on account of their Confucian beliefs, skeptical of the existence of human rights, and believe that asserting or recognizing rights is morally wrong—concede that in the workplace, they are morally obligated to recognize rights? Alan Strudler has recently argued that such is the case. In this article, I argue that because Confucian rights skeptics locate wrongness in inconsistency with the idea of “Confucian community,” Confucian community should be viewed as a moral ideal. I (...) then argue that Confucian rights skeptics ought to act in a manner that is consistent with this ideal, even when the ideal has not yet been realized, just as Kantians ought to act consistently with the Kantian kingdom of ends ideal. Accordingly, contrary to Strudler, I argue that Confucian rights skeptics need not concede that they are morally obligated to recognize rights in the workplace. This conclusion suggests the need for inquiry into the metaphysical foundations of these conflicting views. However, such inquiry is commonly thought to lie beyond the scope of philosophical business ethics proper. I conclude the article by suggesting a number of reasons for business ethicists to consider rejecting the prevalent narrow conception of the scope of the discipline. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

I address the problem of how to locate "traitorous" subjects, or those who belong to dominant groups yet resist the usual assumptions and practices of those groups. I argue that Sandra Harding's description of traitors as insiders, who "become marginal" is misleading. Crafting a distinction between "privilege-cognizant" and "privilege-evasive" white scripts, I offer an alternative account of race traitors as privilege-cognizant whites who refuse to animate expected whitely scripts, and who are unfaithful to worldviews whites are expected to hold.

If the argument of this short study is sound, we have here a point of view which needs to be borne in mind as an aid to the solution of, not only textual and literary problems, but even more those problems which are associated with the attempt to employ such terms as 'polytheism' and 'monotheism' in connexion with Israelite thought, and also those which are inherent in the question of the prophetic psychology or, again, that of revelation. It may also (...) be argued that along this line we gain a new approach to the New Testament extension of Jewish Monotheism in the direction of the later Trinitarianism. . . . At any rate, we can see how it was possible for a Jewish Christian to relate his Messiah so closely with the divine Being as to afford a basis for the later (and Greek) metaphysical formulation of the doctrine of the Trinity. --from the author's conclusions. (shrink)

The book develops a comprehensive and measured case that bitcoin is a net benefit to the world, despite its imperfections. Resistance Money is intended for all, from the clueless to the specialist, from the proponent to the die-hard skeptic, and everyone in between.

The main question of this study is whether God has a personality. We show what the question means, why it matters, and that good sense can be made of an affirmative answer to it. A God with personality — complete with particular, sometimes peculiar, and even seemingly unexplainable druthers — is not at war with maximal perfection, nor is the idea irredeemably anthropomorphic. And the hypothesis of divine personality is fruitful, with substantive consequences that span philosophical theology. But problems arise (...) here too, and new perspectives on inquiry itself. Our cosmos is blessed with weirdness aplenty. To come to know it is nothing less than to encounter a strange and untamed God. (shrink)

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY (...) Acad Sci 959, 452–462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it. BioEssays 24:667–676, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Humans are an exceptionally cooperative species, but there is substantial variation in the extent of cooperation across societies. Understanding the sources of this variability may provide insights about the forces that sustain cooperation. We examined the ontogeny of prosocial behavior by studying 326 children 3–14 y of age and 120 adults from six societies (age distributions varied across societies). These six societies span a wide range of extant human variation in culture, geography, and subsistence strategies, including foragers, herders, horticulturalists, and (...) urban dwellers across the Americas, Oceania, and Africa. When delivering benefits to others was personally costly, rates of prosocial behavior dropped across all six societies as children approached middle childhood and then rates of prosociality diverged as children tracked toward the behavior of adults in their own societies. When prosocial acts did not require personal sacrifice, prosocial responses increased steadily as children matured with little variation in behavior across societies. Our results are consistent with theories emphasizing the importance of acquired cultural norms in shaping costly forms of cooperation and creating cross-cultural diversity. (shrink)

I Am grateful for the honour of being invited to give the second Manson Lecture. Dr. Manson believed that the study of sick people leads into the widest fields of thought, but that increasing specialization within medicine diverts the doctor from seeing man and his nature whole: the chief question seems to be , “whether medicine is in the bondship of practice, whether it is a skilled art, or whether it can emerge to give its own contribution to abstract thought (...) and philosophy.” Indeed, pleading with doctors to join this Institute of Philosophy, he declared that medicine should be the most philosophic of the professions. In this he was reviving an ancient claim: the arguments for it have lately been restated with much Aristotelian piety by Scott Buchanan. Now here I find myself in a difficulty at the outset: I am to speak of the relationship between philosophy and medicine, at a lecture founded by a passionate believer in their conjunction, yet I am engaged in a particular branch of medicine which was for longer than any other preoccupied with philosophy and dependent on it, but had so little profit from its fidelity that it reckons progress from the time when it struggled away from this allegiance. Psychiatry has not been able to refrain since then from many a backward glance at the older philosophy she once swore by, and she has been much influenced by the philosophies of later times: she has—doubtless in punishment for her defection—become entangled now and then in bad, unrecognized philosophy of her own making. She has, at all events, never achieved more than a temporary indifference to philosophic thought. (shrink)

Many translations have been made from the original Sanskrit of the Yoga Sutras of Patanjali. They have become well loved, well used, and well applied by many in all parts of the world and of all religious beliefs. The Sutras have a power and a timelessness about them which demonstrate the accuracy with which they pinpoint the basic truths of human evolution from subservience to personality clamours to the serene freedom of the soul. Most human problems today originate in selfish (...) desire; the prostitution of the feeling nature to self-centred physical appetites. This is also brought out clearly in the teaching of the Lord Buddha, the treading of the Noble Eight-Fold path providing the only way out of the maze: Right Values; Right Speech; Right Mode of Living; Right Thinking; Right Expression; Right Conduct; Right Effort; Right Rapture or True Happiness. These are attributes of the soul. Patanjali explores exhaustively the means, the techniques and the mental posture which create the connecting thread between the form-centred personality and these stages towards spiritual achievement and soul fusion. The four parts of the book develop: 1. The Problem of Union (51 sutras). 2. sutras). 4. Illumination (34 sutras). Many different training techniques have been available over the centuries, depending on the condition of human consciousness and the phase of spiritual growth to be accomplished. Each Yoga has had its place, fulfilled its function, and become an absorbed part of human experience. In this book the factor of mind in meeting present-day needs is again given prominence as the agent of the soul, and the key to personality release. These Yoga Sutras of Patanjali are based on Raja Yoga, the kingly science of the soul: Through the science of Raja Yoga the mind will be known as the instrument of the soul and the means whereby the brain of the aspirant becomes illuminated and knowledge gained of those matters which concern the realm of the soul. The soul is concerned with the working out of planetary purpose and plan; so again we find that mental training, and the self-achievement of the individual, lead to cooperation and service on a scale far more comprehensive and of far greater evolutionary significance than merely the individual effects on the life of the disciple. venture on the path of union with the soul. When through the removal of hindrances and the purification of the sheaths, the totality of knowledge becomes available, naught further remains for the man to do. (shrink)

If there actually is a third wave of feminism, it is too close to the second wave for its definition to be clear and uncontroversial, a fact which emphasizes the political nature of declaring the existence of this third wave. Through an examination of some third wave literature, a case is made for emphasizing the continuity of the second and third waves without blurring the differences between older and younger feminists.

The election of President Donald Trump, through his campaign of race-baiting, sexual harassment, and blatant disregard for human decency, lowered the moral bar of American public discourse. Julius Bailey’s latest book discusses the current state of hypocrisy and mistrust in the American political system, especially as these affect ethnic minorities and low-income groups. In powerful and inspiring prose, Bailey writes with a voice well informed by current events, empirical data, and philosophical observation. Bailey looks at the causes (...) and consequences of this new era and applies his passionate yet astute analysis to issues such as hate speech, gerrymandering, the use of the Confederate flag, and America’s relationship with the gun. _A percentage of the revenue from this book’s sales will be donated to two organizations: The Movement for Black Lives and Color of Change._. (shrink)

This book has its philosophical starting point in the idea that group-based social movements have positive implications for peace politics. It explores ways of imagining community, nation, and international systems through a political lens that is attentive to diversity and different lived experiences. Contributors suggest how groups might work toward new nonviolent conceptions and experiences of diverse communities and global stability.

... CHAPTER 1 Philosophy Philosophy, at least according to the origin of the word in classical Greek, is the "love of wisdom" — philosophers are lovers of ...