Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current curative options (...) of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases. (shrink)

The cosmological constant problem arises at the intersection between general relativity and quantum field theory, and is regarded as a fundamental problem in modern physics. In this paper, we describe the historical and conceptual origin of the cosmological constant problem which is intimately connected to the vacuum concept in quantum field theory. We critically discuss how the problem rests on the notion of physically real vacuum energy, and which relations between general relativity and quantum field theory are assumed in order (...) to make the problem well-defined. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:“An Immoderate Taste for Truth”: Censoring History in Baudelaire’s “Les bijoux”E. S. Burt (bio)In May 1949, a French Court of Appeals reversed an 1857 decision condemning six poems from Les fleurs du mal for obscenity, in a signal case of a public lifting of a ban against some lyric poems. 1 Among the several interesting features of this case not the least is the decision to proceed against the (...) work in the first place. For lyric poetry does not appear an attractive target for censorship. Its subject matter and formalism remove it far enough from the experience of most readers that Gustave Flaubert, fresh from his troubles with the court over Madame Bovary, could express his surprise at the government’s attack: “This is new,” he wrote to Baudelaire, “this pursuit of a volume of verse.” While Flaubert’s comment was in point of fact inaccurate, he puts his finger on a problem worth considering. 2 Here we have a work that must seem naturally exempt from state intervention, by virtue of a deliberate retreat from risky political subjects, and it nonetheless did get censored by the state. Can anything be learned about “normal” state censorship from this exceptional case? [End Page 19]A key factor in the government’s decision to pursue the book, according to the prosecutor Pinard, was that these poems would prove accessible to a large audience: 3 “An immoral book that had no chance of being read or understood would not be pursued” [1208], he states. In his argument, as in the judgment by the court that the condemned poems “lead necessarily to the exciting of the senses by a coarse realism offensive to modesty” [1182], the assumption is that the work is extraordinarily available, its pictures immediately referable to ordinary experience. In the six condemned poems, language is judged to be not a veil but a tool, and a sex tool at that. “Despite an effort of style” [1182], the poetic situation—in most of the poems that of the boudoir—is painted in a language insufficiently flowery. 4A further interesting feature in the case is that when it comes up again, under DeGaulle’s Fourth Republic, the court summarily dismisses the 1857 judgment of coarse realism as just one possible interpretation, and a forced one at that. Instead, the 1949 court finds that the poems are self-referential, symbolic entities that do not represent ordinary experience:If some pictures, on account of their originality, were able to alarm some minds upon first publication and appeared to the first judges as offensive to morality, such an appraisal, attaching itself only to a realistic interpretation of the poems and neglecting their symbolic meaning, has proved to be of an arbitrary character, unratified by public opinion or by the judgment of the literary world.[St. John-Stevas 249]The shocking representations of 1857, outraging morality, are now understood to deliver the Wordsworthian “shock of mild surprise” by which we recognize the original work of art. In 1949, the poems are precious artifacts; their language is not realistic but symbolical; its sensuous forms reveal an inner, spiritual meaning.A crucial resemblance can be discerned between the actions taken by the two courts: both make their judgments in terms of a “reading pact,” a set of “artificial rules” [1206] that are presumed to govern reading and to have currency in the context. Les fleurs gets policed in the name of this generic purity, with the prosecutor Pinard calling “the judge... a sentinel who must not let the border be crossed” [1206] and the 1949 decision confirming the opinion of the literary world that the supposed transgression against public morality was in point of fact a transformation in the rules regulating the narrow confines of lyric poetry. 5This concern that texts be framed by a reading pact aimed at constraining their interpretation is worth considering in any discussion of censorship that wants to move from the level of pragmatics to that of theory. It leads to queries about the possibility of getting rid of state censorship entirely and about the state’s interest, as guardian and overseer of the archive, in the institutionalization and... (shrink)

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 2199-2664 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

This study explored possible deficits in selective attention brought about by Dementia of Alzheimer Type (DAT). In three experiments, we tested patients with early DAT, healthy elderly, and young adults under low memory demands to assess perceptual filtering, conflict resolution, and set switching abilities. We found no evidence of impaired perceptual filtering nor evidence of impaired conflict resolution in early DAT. In contrast, early DAT patients did exhibit a global cost in set switching consistent with an inability to maintain the (...) goals of the task (mental set). We discuss these findings in relation to the DAT literature on executive attention, dual-tasking, and working memory. Ó 2007 Elsevier Inc. All rights reserved. (shrink)

A scholarly edition of The Clarendon Edition of the Works of John Locke: Correspondence: Letters 849-1241 by E. S. de Beer. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

Philosophical instruction in the French Universities usually consists in more or less direct preparation for the licence-ès-lettres and the agrigation , or in informal discussion with candidates preparing for the Doctorate. But it has for long been the practice at the Sorbonne in Paris for the Professors to deliver a course of public lectures lasting throughout a half or the whole of the academic year. And since the eleinehts of logic and philosophy are taught in the top form of every (...) lycèe quite a large part Of the ordinary educated public is able to follow with profit the communications of the foremost philosophers. This year, Professor A. Lalande lectures on “General Methodology”; Professor Brunschvicg on “The Object in Perception and in Science”; Professor Delacroix on “Consciousness and Personality”; Dr. Wallon on “Explanation and Constructive Thought in the Child”; Professor Basch on “The Æsthetic Categories,” and on “English Æsthetics in the Eighteenth Century,” and Professor E. Gilson on “The Main Problems of Mediaeval Philosophy.” At the College de France, Professor Le Roy lectures on “The Primitive Forms of Intelligence,” Professor Pierre Janet on “The Psychological Evolution of Personality,” and Professor Pièron on “Pain and Affective Reactions.”. (shrink)