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: The Nature of Beauty Truth, Goodness, and Beauty Beauty and the Blues Notes.

The approach to critical realism, by D. Drake.--Pragmatism versus the pragmatist, by A. O. Lovejoy.--Critical realism and the possibility of knowledge, by J. B. Pratt.--The problem of error, by A. K. Rogers.--Three proofs of realism, by G. Santayana.--Knowledge and its categories, by R. W. Sellars.--On the nature of the datum, by C. A. Strong.

This paper briefly examines the topic of business ethics and attempts to suggest a code of ethics for multinational firms. While most companies have basic policies on employee integrity, confidentiality and sexual harassment, relatively few have established policies regarding bribery, exploitive child labor, human rights violations and other issues they may encounter in the global market place (Drake, 1998). Until recently, very few companies had truly global operations. Consequently little attention was paid to the issue of ethical guidelines in (...) a global context. Recent changes in international markets have led to an explosion of corporations with global operations, and the need for a global code of ethics has grown commensurately. In this paper we explore the issue of global business ethics and attempt to provide a framework for future discussion. We also examine some of the unique difficulties surrounding the development of any set of global business standards. Key among these difficulties is the issue of competing ethical values in home and host countries. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Imagined Apotheoses: Drake, Harriot, and Ralegh in the AmericasWilliam M. HamlinPerhaps the two best known stories of Europeans being taken for gods by non-European peoples are those of Hernan Cortés in Mexico and Captain James Cook in Hawaii. Separated by two hundred sixty years, five thousand miles, and vast differences in cultural and linguistic context, these two incidents nonetheless share many traits in the conventional telling. Cortés and (...) Cook were both strong leaders, for instance, both capable of inspiring devotion among their subordinates. Both men became amateur ethnographers during their lengthy sojourns away from Europe, both sought to promote an image of respectful rather than rapacious foreign incursion, and both are said to have been taken for returning gods by the native peoples among whom they landed: Cortés for the Toltec culture-hero and demigod Quetzalcoatl, Cook for the Hawaiian deity Lono. Click for larger view View full resolutionFigure 1.“The Far Side” cartoon by Gary Larson. Courtesy of Chronicle Features, San Francisco.Recent scholarly studies and debates—among them the rather strident dispute between Gananath Obeyesekere and Marshall Sahlins over the alleged deification of Cook by eighteenth-century Hawaiians—have opened up these returning-god theories to skeptical critique and detailed justification; but such discussions have had little, if any, impact on popular imagination. 1 [End Page 405] Indeed, the idea that redoubtable European explorers can be (and often are) perceived as supernatural beings by non-European “primitives” has been uncritically perpetuated to this day by filmmakers, fantasists, writers of popular history, and purveyors of cultural literacy. E. D. Hirsch, Jr., for instance, informs our children that Caribbean islanders encountered by Columbus “asked if he had come from heaven”—the implication being, of course, that they took him for a god. 2 And in the recent film, 1492: Conquest of Paradise, we hear the indefatigable Admiral (played by Gerard Depardieu) claim that “on every island the natives welcome us with great generosity and trust.... Because of our appearance, we have been mistaken for gods, and are treated accordingly.” 3 Fortunately, we also have a “Far Side” parody of the cultural conceit on which such ideas in part rely, but the cartoon serves as well to demonstrate just how thoroughly the conceit has permeated our collective awareness (see figure 1). 4 Click for larger view View full resolutionFigure 2.“It’s against my programming to impersonate a deity.” From The Return of the Jedi, dir. Richard Marquand, Lucasfilm, Ltd., 1983. All Rights Reserved. Courtesy of Lucasfilm, Ltd.Let me offer just one other example. Near the end of the popular 1983 film The Return of the Jedi, the forest-dwelling Ewoks begin to chant and salaam upon first glimpsing the golden robot C-3PO, who in turn tells his captured comrades, “I do believe they think I am some sort of god.” When Han Solo sarcastically asks the robot to use his “divine influence” to help extricate them from their predicament, C-3PO replies that such an action would be improper: “It’s against my programming to impersonate a deity.” Here we see, embedded within a film romance, both the classic trope of the apotheosized foreigner and the related motif of the foreigner’s reluctance to [End Page 406] play the god-role (see figure 2). It is worth noting, however, that while C-3PO may be unwilling to exploit the Ewoks’ misperception, Luke Skywalker is not; he uses the “Force” to convince the Ewoks of the robot’s magical prowess and, more to the point, to perpetuate their misapprehension. 5What I wish to suggest in this essay is that certain habitual Western assumptions or conceits regarding cross-cultural encounters—assumptions which have been usefully termed “myth models” inasmuch as they condition human perception and find frequent discursive expression—coexist easily but in fact disjunctively with certain other ideological structures in many early modern travel narratives and colonial accounts. Obeyesekere, in his provocative book on the supposed deification of Captain Cook in Hawaii, has linked such myth models to the conceptual structures of the longue durée as characterized by Fernand Braudel, and it is possible that they may also be... (shrink)

De Interpretatione is among Aristotle's most influential and widely read writings; C. W. A. Whitaker presents the first systematic study of this work, and offers a radical new view of its aims, its structure, and its place in Aristotle's system. He shows that De Interpretatione is not a disjointed essay on ill-connected subjects, as traditionally thought, but a highly organized and systematic treatise on logic, argument, and dialectic.

This article takes up the question of how to facilitate substantive inclusion in deeply divided societies. Turning to deliberative democracy and consociationalism, we find that there is a surprising amount of overlap between the two potentially contradictory models of inclusion. We consider the deliberative potential of consociational institutions that not only address majority and minority relations, but that also find ways to include minorities within minorities. To this end, we examine the institutions that make up a consociation and recommend a (...) two-stage approach to deliberation that facilitates the articulation of public reasons in political decision-making. We argue that extending broad inclusion in an initial stage of deliberations where people do not have to adhere to the criterion of public reason avoids pre-emptive exclusions, while introducing this criterion in a second, decision-making stage of deliberations retains the benefits of deliberative democracy. This two-stage approach addresses the democratic concerns in consociational democracy vis-à-vis minority groups and in deliberative democracy vis-à-vis marginalized groups (that is, minorities within minorities). We argue that adopting this two-stage approach will deepen the level of inclusion found within consociational democracies and widen the applicable scope for deliberative democracy, which is often thought most amenable to small-scale decision-making. (shrink)

This study asks after the fate of sophistry in the Eleatic Stranger's investigation of the best of the six regimes governed by law, and outlines as far as possible the role of the rhetor under the supervision of the true statesman, as well as the function and effects of myth on the citizens of the best regime. In short, I argue that Socrates' competitors do, in a qualified manner, still have a place in such a polis precisely where the work (...) of gathering intelligence finds its civic limit. (shrink)

An affectionate and thoughtful look at the history of county fairs and their tradition and persistence today reveals the county fair as an important institution that helped define America as a nation of free-thinking, self-reliant, and ...

The authors present a case study involving truth telling responsibilities in the setting of nonepileptic seizures. Specifically, over the course of several suspected nonepileptic seizures, a patient’s seizures stopped after he received a saline flush meant to precede the administration of anti-seizure medication. The patient and his surrogate believed he had received the medication each time, and the team wondered whether they should disclose the truth. Some worried that disclosure would reinforce the suspected psychogenic behavior, exacerbating the patient’s condition. In (...) this way, the case study presents a twist on the traditional truth telling archetype. While most truth telling cases center on navigating cultural differences or worries about emotional harm, this case presented concerns about medical harm in the form of exacerbating the patient’s condition. The authors describe the complex patient-family-team dynamic that preceded this ethical dilemma, describe the case, analyze the ethical issue, and describe the outcome. (shrink)

In a recent response to Persson & Savulescu’s Unfit for the Future, Nicholas Agar argues that moral bioenhancement is dangerous. His grounds for this are that normal moral judgement should be privileged because it involves a balance of moral subcapacities; moral bioenhancement, Agar argues, involves the enhancement of only particular moral subcapacities, and thus upsets the balance inherent in normal moral judgement. Mistaken moral judgements, he says, are likely to result. I argue that Agar’s argument fails for two reasons. Firstly, (...) having strength in a particular moral subcapacity does not necessarily entail a worsening of moral judgement; it can involve strength in a particular aspect of morality. Secondly, normal moral judgement is not sufficiently likely to be correct to be the standard by which moral judgements are measured. (shrink)

Both Carnap and Quine made significant contributions to the philosophy of mathematics despite their diversedviews. Carnap endorsed the dichotomy between analytic and synthetic knowledge and classified certainmathematical questions as internal questions appealing to logic and convention. On the contrary, Quine wasopposed to the analytic-synthetic distinction and promoted a holistic view of scientific inquiry. The purpose of thispaper is to argue that in light of the recent advancement of experimental mathematics such as Monte Carlosimulations, limiting mathematical inquiry to the domain of (...) logic is unjustified. Robustness studies implemented inMonte Carlo Studies demonstrate that mathematics is on par with other experimental-based sciences. (shrink)

To assess ethics pedagogy in science and engineering, we developed a new tool called the Engineering and Science Issues Test. ESIT measures moral judgment in a manner similar to the Defining Issues Test, second edition, but is built around technical dilemmas in science and engineering. We used a quasi-experimental approach with pre- and post-tests, and we compared the results to those of a control group with no overt ethics instruction. Our findings are that several stand-alone classes showed a significant improvement (...) compared to the control group when the metric includes multiple stages of moral development. We also found that the written test had a higher response rate and sensitivity to pedagogy than the electronic version. We do not find significant differences on pre- test scores with respect to age, education level, gender or political leanings, but we do on whether subjects were native English speakers. We did not find significant differences on pre- test scores based on whether subjects had previous ethics instruction; this could suggest a lack of a long-term effect from the instruction. (shrink)

Postcolonial science studies entails ostensibly contradictory critical and empirical commitments. Science studies scholars influenced by Bruno Latour and Isabelle Stengers embrace forms of realist, radical empiricism, while postcolonial studies scholars influenced by Jacques Derrida trace the limits of the knowable. This essay takes their common use of the term cosmopolitics as an unexpected point of departure for reconciling Derrida’s program with Stengers’s and Latour’s. I read Derrida’s critique of hospitality and Stengers’s and Latour’s ontological politics as necessary complements for conceiving (...) a care-oriented subalternist cosmopolitics, a process of composing common worlds that remains attentive to the limits of representation. (shrink)

Do famous athletes have special obligations to act virtuously? A number of philosophers have investigated this question by examining whether famous athletes are subject to special role model obligations (Wellman 2003; Feezel 2005; Spurgin 2012). In this paper we will take a different approach and give a positive response to this question by arguing for the position that sport and gaming celebrities are ‘ambassadors of the game’: moral agents whose vocations as rule-followers have unique implications for their non-lusory lives. According (...) to this idea, the actions of a game’s players and other stakeholders—especially the actions of its stars—directly affect the value of the game itself, a fact which generates additional moral reasons to behave in a virtuous manner. We will begin by explaining the three main positions one may take with respect to the question: moral exceptionalism, moral generalism, and moral exemplarism. We will argue that no convincing case for moral exemplarism has thus far been made, which gives us reason to look for new ways to defend this position. We then provide our own ‘ambassadors of the game’ account and argue that it gives us good reason to think that sport and game celebrities are subject to special obligations to act virtuously. (shrink)