Mitochondria contain a molecular genetic system to express the 13 protein components of the electron transport system encoded in the mitochondrial genome (mtDNA). Defects in the function of this system result in some diaseases, many of which are multisystem disorders, prominently involving highly aerobic, postmitotic tissues. These defects can be caused by large‐scale rearrangements of mtDNA, by point mutations, or by nuclear gene mutations resulting in abnormalities in mtDNA. Although any of these mutations would be expected to produce a similar (...) clinical phenotype by compromising oxidative phosphorylation, the surprising and puzzling result is that different clinical phenotypes are generally associated with specific mtDNA mutations. Moreover, the same mutation can produce a distinct clinical phenotype in different individuals or pedigrees. MtDNA rearrangements are also found in aged individuals, but at a subclinical level, suggesting that normal and pathological processes can differ by the effect of genetic or environmental factors on the error rate of mtDNA replication. (shrink)

This collection of interdisciplinary essays on a unique work by a physician and political figure in 12th-century Spain and North Africa casts important light on the social and intellectual history of the period and breaks new ground in the critical assessment of medieval Arabic literary works.

El nuevo libro de Xavier de Planhol, L'Islam et la mer es el primer intento, por parte de un especialista occidental, de evaluar el papel del mar en el mundo islámico. No es un libro que se dedique a describir acontecimientos sino a establecer paradigmas culturales e intelectuales, llegando a la conclusión de que «el islam es incompatible con el mar». En consecuencia, explora las implicaciones de esta antipatía a lo largo de la historia islámica desde tiempos pre-islámicos hasta el (...) presente. Su tesis, sin embargo, puede ser cuestionada desde diversas perspectivas, y este artículo, a la vez reseña y estado de la cuestión, sugiere aspectos en los que, tanto las fuentes que él cita, como otras no utilizadas en el libro, pueden ser interpretadas para llegar a conclusiones muy diferentes. (shrink)

Insect molting is elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands. Ecdysteroid synthesis in the prothoracic glands is controlled in large measure by a peptide hormone from the brain, prothoracicotropic hormone (PTTH), which exists in two forms and is released into the general circulation as a result of environmental and developmental cues. The means by which PTTH activates the prothoracic glands has been examined at the cellular level and the data reveal the involvement of (...) cAMP, calcium, calmodulin, cAMP‐dependent protein kinase and the ultimate phosphorylation of a 34 kDa protein tentatively identified as ribosomal protein S6. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

During the years 1814–1819, William Higgins, an Irish chemist who worked at the Dublin Society, claimed he had anticipated John Dalton in developing the atomic theory and insinuated that Dalton was a plagiarist. This essay focuses not on William Higgins, but on his uncle Bryan Higgins, a well-known chemist of his day, who had developed his own theories of caloric and chemical combination, similar in many respects to that of Dalton. New evidence is first introduced addressing Bryan's disappearance from the (...) scientific community after 1803. In his later years, Bryan apparently suffered from a condition resulting in a decline in his mental health, which explains why he never lodged any priority claims of his own against Dalton, or defended those of his nephew. Dalton's mention of Bryan's name in Part II ofA New System of Chemical Philosophy, his laboratory notebook entries, and a fresh look at his correspondence with chemist Thomas Charles Hope indicate that Dalton adopted a Higgins-like caloric model in 1803. Together these factors provide evidence to support the argument that Dalton learned of Bryan's theories via a meeting he had with William Allen on 10 July 1803. Existing evidence related to the origin of the atomic theory is worthy of re-examination in light of Dalton's possible prior knowledge of Bryan's work. (shrink)

Mindfulness, derived from Buddhist psychology and philosophy, has gained broad popularity in the last decades, due importantly to scientific interest and findings. Yet Buddhist mindfulness developed in Asian pre-scientific culture and religion, and is predicated upon long-term cultivation of introspective awareness of lived experience, not highly accessible to empirical study. Further complicating the ‘science' of mindfulness, mindfulness's very definition is multifaceted, resistant to dismantling and requires substantial amounts of personal practice to gain expertise. Most scientists investigating mindfulness have not achieved (...) a high level of this expertise. Here I address how mindfulness is currently being invented as a scientific fact or object of inquiry. The intrinsic porosity of subjective and objective factors influencing the investigation of mindfulness is highlighted: the evolving body of ‘scientific' experts, instruments used to measure mindfulness, the alliances of funders and other supporters of mindfulness research, and the public representation of the related findings. (shrink)

In some part, the ideas presented here are anticipated in a paper by Frank Tillman, through I present a broader theory intended to have utility in connection with the theory of truth.

I propose that primary conscious awareness arises from synchronized activity in dendrites of neurons in dorsal thalamic nuclei, mediated particularly by inhibitory interactions with thalamic reticular neurons. In support, I offer four evidential pillars: consciousness is restricted to the results of cortical computations; thalamus is the common locus of action of brain injury in vegetative state and of general anesthetics; the anatomy and physiology of the thalamus imply a central role in consciousness; neural synchronization is a neural correlate of consciousness.

We show the existence of Lorentz invariant Berry phases generated, in the Stueckelberg–Horwitz–Piron manifestly covariant quantum theory (SHP), by a perturbed four dimensional harmonic oscillator. These phases are associated with a fractional perturbation of the azimuthal symmetry of the oscillator. They are computed numerically by using time independent perturbation theory and the definition of the Berry phase generalized to the framework of SHP relativistic quantum theory.

Recent advances in Artificial Intelligence and their application within the field of mental health provision raise issues that cross social, economic, and philosophical boundaries. While Therapeutic A.I. promises to disrupt the current provision of mental health services to reach populations without access to adequate mental health care there are risks. This paper addresses the philosophical problems posed by Therapeutic A.I. I suggest that in the absence of legal guidelines there is a need for philosophical guidance that prioritizes the dignity of (...) clients/consumers. To that end, I advance Rosen’s concept of dignity-as-respectfulness as the most appropriate philosophical principle to guide the application of Therapeutic A.I. (shrink)

How is it that sounds from the mouth or marks on a page—which by themselves are nothing like things or events in the world—can be world-disclosive in an automatic manner? In this fascinating and important book, Lawrence J. Hatab presents a new vocabulary for Heidegger’s early phenomenology of being-in-the-world and applies it to the question of language. He takes language to be a mode of dwelling, in which there is an immediate, direct disclosure of meanings, and sketches an extensive (...) picture of proto-phenomenology, how it revises the posture of philosophy, and how this posture applies to the nature of language. Representational theories are not rejected but subordinated to a presentational account of immediate disclosure in concrete embodied life. The book critically addresses standard theories of language, such that typical questions in the philosophy of language are revised in a manner that avoids binary separations of language and world, speech and cognition, theory and practise, realism and idealism, internalism and externalism. (shrink)

Critics have charged that Heidegger's account of authenticity is morally nihilistic, that his fundamental ontology is either egocentric or chauvinistic; and many see Heidegger's turn to Nazism in 1933 as following logically from an indifference, and even hostility, to "otherness" in the premises of his early philosophy. In_ The Fragile "We": Ethical Implications of Heidegger's "Being and Time,"_ Lawrence Vogel presents three interpretations of authentic existence--the existentialist, the historicist, and the cosmopolitan--each of which is a plausible version of the (...) personal ideal depicted in _Being and Time._ He then draws parallels between these interpretations and three moments in the contemporary liberal-communitarian debate over the relationship of the "I" and the "We." His book contributes both to a diagnosis of what there is about _Being and Time_ that invites moral nihilism and to a sense of how fundamental ontology might be recast so that "the other" is accorded an appropriate place in an account of human existence. (shrink)

Media, politicians, and individuals often use the term "racism" casually and inaccurately, threatening to strip the concept of its meaning and moral force, argues Blum in "'I'm Not a Racist, But...': The Moral Quandary of Race". Not all racial incidents are racist incidents. Blum asserts that only "certain especially serious moral failings and violations" merit the designation "racism." Discussing various scholarly perspectives on the construction of racial categories, Blum calls for a balance between "ridding ourselves of the myth of race" (...) and understanding the role of race in social inequality and in history. He discusses the history and genesis of the idea of race, moral asymmetries between whites and non-whites, and blacks and non-blacks in racial incidents; institutional racism; the nature of racial discrimination; and other topics. (shrink)

Aquinas’s Five Ways are not to be understood as demonstrative proofs, successful or not, for the existence of God. Rather, they provide a necessary step towards supplying licensable surrogates for the essential predications that cannot logically be drawn from the incomprehensible nature of God, yet would seem needed for the Summa’s declared genre of argued theology. (Predication secundum analogiam provides surrogates for non-relational accidental predications, likewise unavailable.) What Aquinas is proving in arguing deum esse in ST I.2.3 is not God’s (...) actual existence (see ST I.3.4 ad 2) but an alternative interpretation of “God’s being something” where “God is something” is a placeholder for, say, “God is prime mover” or, more explicitly, for such (necessary) identities as “The prime mover is the necessitated necessitator,” an identity whose necessity depends at more than one place on the assumption of God’s existence from faith, not on demonstrative proof of God’s existence. (shrink)

I defend the doctrine of double effect and a so-called ‘strict’ definition of intention: A intends an effect if and only if A has it as an end or believes that it is a state of affairs in the causal sequence that will result in A's end. Following Kamm's proposed ‘doctrine of triple effect’, I distinguish an intended effect from an effect that motivates an action, and show that this distinction is morally significant. I use several contrived cases as illustrations, (...) but my position does not depend on intuitive judgements about them. Instead, it follows from the view that the moral permissibility of an action depends at least partly on how it forms the agent's character. I also respond to some objections presented by Harris, Bennett, McIntyre, Thomson and Scanlon to the doctrine of double effect. (shrink)

Naturalists tell us to rely on what science tells about the world and to eschew aprioristic philosophy. But foundational physics relies internally on modes of thinking that can only be called philosophical, and philosophical arguments rely upon what can only be called scientific inference. So what, then, could the naturalistic thesis really amount to?

In this paper, I want eventually to get around to proposing a criterion of identity for events which are changes in physical objects, where events are construed as comprising a distinct metaphysical category of thing. The proposal will be preceded by a discussion of what I take to be a mistaken suggestion for such a criterion; I will do that because I think that seeing what it takes to show why that suggestion fails helps to motivate a theory about what (...) it is to be an event; and that theory wi II supply the conceptual foundations for my proposal concerning the criterion of identity for events. Before that suggestion is discussed, however, I want to discuss briefly an aspect of the question, Why do we have to give a criterion of identity for events, or for objects of any sort whatsoever? I want to have a brief look at the connection between identity criteria and the idea of a kind of object. (shrink)

I argue that physicians can save women from life-threatening pregnancies by performing a craniotomy, placentectomy, or salpingotomy without intending death or harm. To support this conclusion, I defend the relevance thesis about intentions (a person intends X only if X explains the action). I then criticize the identity thesis (if a person intends X and knows X is Y then the person intends Y) and three mistakenly strict moral principles: (1) one may not intend something that is a serious harm (...) for an innocent person, (2) one may not intend to terminate pregnancy before viability, which would prohibit, and (3) one may not act on a person’s body in a harmful way in order to benefit another person. (1) would prohibit procuring organs from living donors, (2) would prohibit treating hepatic pregnancies and other ectopic pregnancies, and (3) would prohibit procuring organs from living donors and performing many prenatal surgeries. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Hegel’s Ladder, Volume I: The Pilgrimage of Reason by Henry Silton HarrisLawrence S. StepelevichHenry Silton Harris. Hegel’s Ladder, Volume I: The Pilgrimage of Reason. Pp. xvi+ 658. Volume II: The Odyssey of Spirit. Pp. xiii + 909. Indianapolis: Hackett Publishing Company, 1997. Cloth, $150.00, the set.This commentary upon Hegel’s Phenomenology of Spirit is the concentrated result of over three decades of sustained study by one of the most (...) renowned of contemporary Hegelian scholars.The Phenomenology stands in the course of philosophic history as (depending upon one’s point of view) either an opportunity or an obstacle—an unavoidable Sphinx. Both admirers and detractors of this famous work will often assign themselves or, more readily, their students, the task of reading it as a introduction to Hegel’s philosophy. However, what occurs is not usually what is intended. After a short perusal, the reader finds that the Phenomenology itself needs an introduction. This need has not been lost on scholars, and their various introductory observations, when expanded and duly annotated, are entered into the ever-growing list of commentaries upon the Phenomenology. Needless to say, given the hundreds of studies which, either in whole or in part, are devoted to commenting upon this work, there are some grand failures, as Lowenberg’s elegantly vapid Dialogues on the Phenomenology, or Heidegger’s inconclusive “critical debate with Hegel.” There are also a few successes, such as Jean Hyppolite’s Genesis and Structure. Without doubt, Harris’s commentary is a success, and surely the most successful of all Anglophone commentaries upon the Phenomenology. [End Page 473]Hegel’s Ladder, which assumes a learned readership, embarks upon the same long and tortured path facing any reader of the Phenomenology. It is no small thing to follow where one thinks Hegel leads, as he had a somewhat perverse tendency to avoid both clarifying examples and a tendency to, as J. N. Findlay described it, “wanton obscurity.” To make matters worse, there is also the complex ordering of the text itself, a palimpsest character which has led more than a few commentators to take the work as a disorderly juvenalia, best left ignored in favor of the more lucid Encyclopaedia. And finally, there is also the extratextual matter of whether or not one “buys into” Hegel’s thought—which Harris does. In any case, a superficial reading will not do, and readers will be reminded of Hegel’s own “path of despair” when they follow the course of Harris’s 1,500-page commentary. It is not an “easy read,” nor could it be.Professor Harris is well aware of the problems confronting any commentator, but addresses them in an way which would assure the reader that the commentary is directly linked to the text, and does not simply follow “paths of one’s own, offering variations, elaborations, and applications instead of faithful analysis” (xii). To this end, a “logical commentary” is developed, one which follows a serial paragraph-by-paragraph analysis of the text. Each paragraph-analysis is referenced to the Phenomenology, which allows the reader a direct reference to Hegel’s own words. These “safe” and constrained analytic paragraphs are each followed by an extensive and free-ranging commentary. The intention of this procedure is not only to assure the reader that Harris’s commentary is textually grounded, but to convince the reader that Harris’s contention regarding the nature of the Phenomenology is correct—that it is a profoundly cohesive and extended logical argument. In short, for Harris, the Phenomenology is exactly what what Hegel claimed it to be: a science of experience. Most commentators have not accepted this claim of either the unity or the logical course of the text, but this “received view” is, for Harris, the “view that I want to challenge and, if possible, to overthrow. If I am right, an acceptably continuous chain of argument, paragraph by paragraph, ought to be discoverable in the text” (xii).In the total context of Hegel’s philosophy, Harris understands the Phenomenology to be the “necessary preamble to speculative logic.” Once this is accepted, then “we ought to know at once, by the simplest of... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Hegel’s Ladder, Volume I: The Pilgrimage of Reason by Henry Silton HarrisLawrence S. StepelevichHenry Silton Harris. Hegel’s Ladder, Volume I: The Pilgrimage of Reason. Pp. xvi+ 658. Volume II: The Odyssey of Spirit. Pp. xiii + 909. Indianapolis: Hackett Publishing Company, 1997. Cloth, $150.00, the set.This commentary upon Hegel’s Phenomenology of Spirit is the concentrated result of over three decades of sustained study by one of the most (...) renowned of contemporary Hegelian scholars.The Phenomenology stands in the course of philosophic history as (depending upon one’s point of view) either an opportunity or an obstacle—an unavoidable Sphinx. Both admirers and detractors of this famous work will often assign themselves or, more readily, their students, the task of reading it as a introduction to Hegel’s philosophy. However, what occurs is not usually what is intended. After a short perusal, the reader finds that the Phenomenology itself needs an introduction. This need has not been lost on scholars, and their various introductory observations, when expanded and duly annotated, are entered into the ever-growing list of commentaries upon the Phenomenology. Needless to say, given the hundreds of studies which, either in whole or in part, are devoted to commenting upon this work, there are some grand failures, as Lowenberg’s elegantly vapid Dialogues on the Phenomenology, or Heidegger’s inconclusive “critical debate with Hegel.” There are also a few successes, such as Jean Hyppolite’s Genesis and Structure. Without doubt, Harris’s commentary is a success, and surely the most successful of all Anglophone commentaries upon the Phenomenology. [End Page 473]Hegel’s Ladder, which assumes a learned readership, embarks upon the same long and tortured path facing any reader of the Phenomenology. It is no small thing to follow where one thinks Hegel leads, as he had a somewhat perverse tendency to avoid both clarifying examples and a tendency to, as J. N. Findlay described it, “wanton obscurity.” To make matters worse, there is also the complex ordering of the text itself, a palimpsest character which has led more than a few commentators to take the work as a disorderly juvenalia, best left ignored in favor of the more lucid Encyclopaedia. And finally, there is also the extratextual matter of whether or not one “buys into” Hegel’s thought—which Harris does. In any case, a superficial reading will not do, and readers will be reminded of Hegel’s own “path of despair” when they follow the course of Harris’s 1,500-page commentary. It is not an “easy read,” nor could it be.Professor Harris is well aware of the problems confronting any commentator, but addresses them in an way which would assure the reader that the commentary is directly linked to the text, and does not simply follow “paths of one’s own, offering variations, elaborations, and applications instead of faithful analysis” (xii). To this end, a “logical commentary” is developed, one which follows a serial paragraph-by-paragraph analysis of the text. Each paragraph-analysis is referenced to the Phenomenology, which allows the reader a direct reference to Hegel’s own words. These “safe” and constrained analytic paragraphs are each followed by an extensive and free-ranging commentary. The intention of this procedure is not only to assure the reader that Harris’s commentary is textually grounded, but to convince the reader that Harris’s contention regarding the nature of the Phenomenology is correct—that it is a profoundly cohesive and extended logical argument. In short, for Harris, the Phenomenology is exactly what what Hegel claimed it to be: a science of experience. Most commentators have not accepted this claim of either the unity or the logical course of the text, but this “received view” is, for Harris, the “view that I want to challenge and, if possible, to overthrow. If I am right, an acceptably continuous chain of argument, paragraph by paragraph, ought to be discoverable in the text” (xii).In the total context of Hegel’s philosophy, Harris understands the Phenomenology to be the “necessary preamble to speculative logic.” Once this is accepted, then “we ought to know at once, by the simplest of... (shrink)

CHAPTER I INTRODUCTION Liberty is perhaps the most praised of all social ideals. Rare is the modern political movement which has not inscribed "liberty," ...

When conceived as an empirical claim, it is natural to wonder how one might test the hypothesis of multiple realization. I consider general issues of testability, show how they apply specifically to the hypothesis of multiple realization, and propose an auxiliary assumption that, I argue, must be conjoined to the hypothesis of multiple realization to ensure its testability. I argue further that Bechtel and Mundale go astray because they fail to appreciate the need for this auxiliary assumption. †To contact the (...) author, please write to: Department of Philosophy, University of Wisconsin–Madison, 5185 Helen C. White Hall, 600 North Park Street, Madison, WI 53706; e‐mail: [email protected]. (shrink)