The emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overcome to fully realise the potential of hPSCs. Details are provided for all disease‐specific human induced pluripotent stem cell lines spanning a dozen dysfunctional organ systems. Phenotype and pharmacology have been examined in only 17 of 63 lines, primarily those that model neurological and (...) cardiac conditions. Drug screening is most advanced in hPSC‐cardiomyocytes. Responses for almost 60 agents include examples of how careful tests in hPSC‐cardiomyocytes have improved on existing in vitro assays, and how these cells have been integrated into high throughput imaging and electrophysiology industrial platforms. Such successes will provide an incentive to overcome bottlenecks in hPSC technology such as improving cell maturity and industrial scalability whilst reducing cost. (shrink)

In works of literary fiction, it is a part of the fiction that the words of the text are being recounted by some work-internal 'voice': the literary narrator. One can ask similarly whether the story in movies is told in sights and sounds by a work-internal subjectivity that orchestrates them: a cinematic narrator. George M. Wilson argues that movies do involve a fictional recounting (an audio-visual narration ) in terms of the movie's sound and image track. Viewers are usually (...) prompted to imagine seeing the items and events in the movie's fictional world and to imagine hearing the associated fictional sounds. However, it is much less clear that the cinematic narration must be imagined as the product of some kind of 'narrator' - of a work-internal agent of the narration. Wilson goes on to examine the further question whether viewers imagine seeing the fictional world face-to-face or whether they imagine seeing it through some kind of work-internal mediation . It is a key contention of this book that only the second of these alternatives allows one to give a coherent account of what we do and do not imagine about what we are seeing on the screen. Having provided a partial account of the foundations of film narration, the final chapters explore the ways in which certain complex strategies of cinematic narration are executed in three exemplary films: David Fincher's Fight Club , von Sternberg's The Scarlet Empress , and the Coen brothers' The Man Who Wasn't There. (shrink)

Jewish law takes an approach to self-defense that differs dramatically from the conventional assumptions of Western secular legal systems. The central theme of Talmudic jurisprudence is that self-defense rests on a duty not to stand idly by while one's neighbor suffers. “Do not stand on the blood of one's neighbor,” as the point is cryptically put in Leviticus 19:16. This way of thinking about self-defense departs in two significant ways from common Western assumptions. First, it stresses that the roots of (...) self-defense are a duty rather than a right to act; second, it treats the case of third-party defense as logically prior to the first-party case of self -defense. (shrink)

The question of reductionism is an obstacle to unification. Many behavioral scientists who study the more complex or higher mental functions avoid regarding them as selected by motivation. Game-theoretic models in which complex processes grow from the strategic interaction of elementary reward-seeking processes can overcome the mechanical feel of earlier reward-based models. Three examples are briefly described. (Published Online April 27 2007).

In the Optics, Descartes claims that telescopes and microscopes lead to morally certain knowledge. It is unclear, however, that Descartes’s expressed confidence in these instruments is warranted. In this article, I show how a limited range of telescope and microscope observations could lead to morally certain knowledge for Descartes, and how observations beyond this range admit of enough reasonable doubt to undermine moral certainty. I also explain moral certainty as a form of knowledge in Descartes’s scientific practices, his epistemic commitment (...) to optical instruments, and I offer an explanation for why Descartes never used optical instruments in his scientific endeavours. -/- ---- -/- Dans la Dioptrique, Descartes prétend que les télescopes et les microscopes donnent accès à des connaissances moralement certaines. Cependant, il n’est pas certain que la confiance accordée par Descartes à ces instruments soit justifiée. Dans cet article, je montre comment une gamme limitée d’observations effectuées à l’aide d’instruments d’optique pourraient mener aux connaissances moralement certaines pour Descartes, et comment d’autres observations allant au-delà de cette gamme introduisent suffisamment de doute raisonnable pour saper cette certitude morale. Enfin, j’interprète la certitude morale comme une forme de connaissance dans l’empirisme de Descartes, j’explique son engagement épistémique envers les instruments d’optique, et j’éclaire les raisons pour lesquelles il n’a jamais employé d’instruments d’optique dans ses propres recherches scientifiques. (shrink)

Based on the ideas of Einstein and Minkowski, this concise treatment is derived from the author's many years of teaching the mathematics of relativity at the University of Michigan. Geared toward advanced undergraduates and graduate students of physics, the text covers old physics, new geometry, special relativity, curved space, and general relativity. Beginning with a discussion of the inverse square law in terms of simple calculus, the treatment gradually introduces increasingly complicated situations and more sophisticated mathematical tools. Changes in fundamental (...) concepts, which characterize relativity theory, and the refinements of mathematical technique are incorporated as necessary. The presentation thus offers an easier approach without sacrifice of rigor. Dover (2014) republication of the edition published by John Wiley & Sons, New York, 1950. See every Dover book in print at www.doverpublications.com. (shrink)

A notion that was prevalent throughout the twentieth century and persists into the present, is that Bonaventure compiled the Legenda maior as a means to make peace between two quarreling factions within the Franciscan order—the Spirituals and the Conventuals.2 Some have suggested a twofold function: "restoration of peace and harmony within the order" and the "[vindication of] the friars in the eyes of the world."3 Others prefer to regard the political implications of the Legenda as incidental, focusing instead on the (...) ways in which it succeeds in capturing the general nature of Franciscan spirituality.4 This article aims to contribute to this conversation by investigating... (shrink)

Child assent is recommended in addition to parental consent when enrolling children in clinical research; however, appreciation and relevance ascribed to these concepts vary in different contexts, and information on attitudes towards storage of biological samples for future research is limited, especially in developing countries. We assessed caregivers’ understanding and appreciation of consent and assent procedures, and their attitudes towards use of stored blood samples for future research prior to enrolling a child in clinical research. A total of 17 in-depth (...) interviews were conducted with primary caregivers of children at enrolment or on the immediate follow-up date. All caregivers recalled significant amount information from the study information sheet and were able to appropriately link such information to the consent process. While all participants confirmed information received prior to blood sampling as adequate, a few noted that the purpose was not sufficiently well communicated. Caregivers felt children were cognitively vulnerable, and prone to decisions that were not necessarily in their best interest. Nearly all caregivers felt it was their right and responsibility to overrule objections from their ward’s regarding enrolment into specific study or receipt of a therapeutic procedure. There were no objections or concerns regarding use of stored biological samples for future research purposes. There is thus, a need to improve understanding of caregivers on the information provided during the informed consent process. Context-specific studies on the age of assent in specific populations are needed. (shrink)

This article discusses the approach of the Clinical Ethics Consultation Advisory Committee (CECA) in developing A Case-Based Study Guide for Addressing Patient-Centered Ethical Issues in Health Care. This article addresses the processes used by the CECA, its use of pivot questions intended to encourage critical reflection, and the target audience of this work. It first considers the salience of case studies in general education and their relevance for training ethics consultants. Second, it discusses the enfolding approach used in presenting the (...) case material designed to engage the trainee in the details of the case while stimulating critical reflection. And, third, this article briefly comments on the target audience with the caveat that even superbly developed cases are prone to misuse, although that prospect should not deter their development. (shrink)

To the extent that acting fairly is in an individual's long-term interest, short-term impulses to cheat present a self-control problem. The only effective solution is to interpret the problem as a variant of repeated prisoner's dilemma, with each choice as a test case predicting future choices. Moral choice appears to be the product of a contract because it comes from self-enforcing intertemporal cooperation.

The aim of this essay is to explore similarities between Whitehead’s stages of education and two of the “ultimate notions” he discusses in Modes of Thought. I hope this exploration will shed light on what Whitehead means when he opens the Epilogue of that book by saying: “The task of a university is the creation of the future, so far as rational thought, and civilized modes of appreciation, can affect the issue” (171).

A standard account of creativity is that it is a process in which the form of a thing or event is altered—restructured or reinterpreted—in a way that changes fundamentally that thing’s or event’s meaning, its nature or function, its intrinsic or instrumental value. What is created in this manner, however, is only a variation of the initial form. Such processes are creative in a weak sense; the strong sense requires that the old form be replaced by a quite different one, (...) as in reconstructions or metaphors. But creative substitution is not haphazard, not a matter of insight, genius, luck, or divine assistance. It utilizes the generative rules governing a formal structure to make or discover new forms that are transformations, not variations, of the original form. These procedures are teachable and not mysterious, although the possible transforms of the structure are never predictable. (shrink)

HISTORIANS DESCRIBE AND EXPLAIN THE PAST. IT IS ARGUED THAT THIS ACTIVITY CAN BE EXTENDED TO ENCOMPASS FUTURE-REFERRING STATEMENTS WITHOUT BECOMING SOOTHSAYING. DESCRIPTIVE AND EXPLANATORY TECHNIQUES ARE EXAMINED, AND THE TEST OF THEIR ADEQUACY SEEN TO INVOLVE SPECULATIVE PREDICTION AND PROJECTION. PHILOSOPHERS OF HISTORY ALSO USE SUCH TECHNIQUES, IMAGINATIVELY COMPLETING INCOMPLETE DESCRIPTIVE PATTERNS BY REFERENCE TO THE FUTURE, IN ORDER TO SUGGEST AND EVALUATE EXPLANATIONS OF PAST EVENTS.

Volume I of two readers containing essential important works on constitutional liberty and the foundations of modern western political theory. This first volume contains works from Socrates through Thomas Jefferson.

The author argues that the theory of a dorsal/ventral stream for visual processing can be used to reconcile the constructivist and direct perception theories. My commentary discusses neurophysiological and psychophysical studies that run counter to the view. In addition, the central issue of debate between the constructionist and direct perception approaches regarding what is visual information is discussed.

The National Commission for the Protection of Human Subjects of Bio-medical and Behavioral Research ended its work by substantially endorsing the status quo which places primary reliance on local Institutional Review Boards for subject protection. This was predictable because of the commission's researcher-dominated composition which permitted it to assume that research is good; experimentation is almost never harmful to subjects; and researcher-dominated IRBs can adequately protect the interests of human subjects. The successor Presidential Commission can learn much by reexamining these (...) premises. (shrink)