The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Analizo en este trabajo el alcance real de la idea de "espíritu del pueblo" en el pensamiento jurídico de F. C. v. Savigny. Sugiero la posibilidad de que las apelaciones al espíritu del pueblo no sean más que una pantalla retórica que encubre una opción de fondo por una visión lógico-sistemática (y ahistórica) del Derecho, en la que jugaría un papel importante la idealización del Derecho romano en cuanto ratio scripta.

O estudo teve como objetivo comparar e correlacionar indicadores de habilidades sociais e do envolvimento de pais com filhos portadores de retardo mental. Participaram 27 casais com filhos portadores de retardo mental. Os pais responderam os questionários "Critério Brasil", "Qualidade da interação f..

The eme r gence of the concept of pr o g ress is cu r rent l y associated with th e Enlightenment o r , going som e w hat further back, with the que r elle des anciens et des modernes in the 1 7 t h centu r y . Y et the notion of pr o g ress can be traced back to a signi f icant l y earlier period: the foundations of a possi b (...) le Christian pr o g ress i vism w ere, in m y opinion, laid b y St. Augustine; this ess a y e xplores its guidelines. J . G. Herde r ' s reaction a g ainst the notion of pr o g ress proposed b y the Enlightenment possesses also a Christian inspiration. While Enlightened pr o g ress i vism conce i v es past cultures as o v ercoming steps in a rising staircase, Herde r , in turn, claims that each of them amounted to a "self-centered sphere" and w as therefore v alua b le in its o wn right. The sense of the e xistence of past generations cannot lie in p a ving the w a y for future ful f illment as this w ould be incompati b le with d i vine l o v e, w hich estimates each of its creatures in its o wn right, as an unrepeata b le ind i vidual. In contrast to Enlightened a r r o g ance (contempt for the "obscurantist" past), Herder presents a "democratic" vi e w of History within w hich all epochs h a v e the same v alue. (shrink)

The aim of this article is to revisit Clement of Alexandria’s Paedagogus 2.5.45-8 discussing whether Clement holds a moderate position οf laughter or, like most early Christians, tends to an “antigelastic” position. Some scholars, such as Stephen Halliwell and Laura Rizzerio, have concluded that Clement holds an intermediate position between an optimistic approach to laughter and its condemnation. However, in this essay we argue that while Clement’s position is not a straightforward antigelastic one, his apparent acceptance of laughter is so (...) narrow that his moderate view ends up being compromised. Ultimately, he is strongly inclined to condemn laughter and to prescribe an ascetic life devoid of laughter. (shrink)

Free speech has historically been viewed as a special and preferred democratic value in the United States, by the public as well as by the legislatures and courts. In 1937, Justice Benjamin Cardozo wrote in Palko v. Connecticut that protection of speech is a “fundamental” liberty due to America's history, political and legal, and he recognized its importance, saying, “[F]reedom of thought and speech” is “the matrix, the indispensable condition, of nearly every other form of freedom.” It is likely (...) notable that in the Bill of Rights free speech is protected in the First Amendment rather than later. (shrink)

This article focusses on the generality of the entities involved in a geometric proof of the kind found in ancient Greek treatises: it shows that the standard modern translation of Greek mathematical propositions falsifies crucial syntactical elements, and employs an incorrect conception of the denotative letters in a Greek geometric proof; epigraphic evidence is adduced to show that these denotative letters are ‘letter-labels’. On this basis, the article explores the consequences of seeing that a Greek mathematical proposition is fully general, (...) and the ontological commitments underlying the stylistic practice. (shrink)

Why are we interested in history at all? Why do we feel the need to distinguish between past and present? In this book, the author argues that the past originates from an experience of rupture separating past and present. Think of the radical rupture with Europe's past that was effected by the French and the Industrial Revolutions. Sublime Historical Experience investigates how the notion of sublime historical experience complicates and challenges existing conceptions of language, truth, and knowledge. These experiences of (...) rupture are paradoxical since they involve both the separation of past and present and, at the same time, the effort to overcome this separation in terms of historical knowledge. The experience unites feelings of loss/pain with those of love/satisfaction, and thus is in agreement with how sublime experience is ordinarily defined. The experience is also precognitive since it precedes historical knowledge. As such it is a challenge to traditional conceptions of the relationship between experience and truth or language. It compels us to disconnect the notions of experience and truth. (shrink)

Lecture I begins with a brief history of changing views on what the Trolley Problem is and attempts to solve it. The lecture then critically examines Judith Thomson’s recent view that a moral distinction between killing and letting die, and between what a conductor of the trolley or a mere bystander may do to save people from the trolley, eliminates what she now thinks of as the Trolley Problem. The last part considers a different argument for the conclusion that Thomson (...) now favors, but ultimately attempts to resurrect the Trolley Problem, suggesting that it is not who turns the trolley that makes the turning permissible. (shrink)

" -- F. Bradford Wallack The twentieth century has seen the greatest innovations in philosophical cosmology since Newton and Descartes, and Alfred North Whitehead was the first and greatest of the philosophers to work out these innovations ...

Philosophy of history is the Cinderella of contemporary philosophy. Philosophers rarely believe that the issues dealt with by philosophers of history are matters of any great theoretical interest or urgency. In their view philosophy of history rarely goes beyond the question of how results that have already been achieved elsewhere can or should be applied to the domain of historical writing. Moreover, contemporary philosophers of history have done desperately little to dispel the low opinion that their colleagues have of them. (...) In this essay I argue that Arthur Danto is the exception confirming the rule, for Danto’s philosophy of representation may help us understand how texts relate to what they are about. The main shortcoming of philosophy of language undoubtedly is that it never bothered to investigate the philosophical mysteries of the text. The writing of history is a philosophical goldmine and we must praise Danto for having reminded us of this. (shrink)

Historians rarely agree with Hayden White's account of their discipline. To a certain extent their dissatisfaction can be explained by the fact that historians customarily distrust historical theory and always tend to look at the historical theorist with the greatest suspicion. But historians find an extra argument for their dislike of White's ideas in his alleged cavalier disregard of how historical facts limit what the historian might wish to say about the past. And, admittedly, this criticism is not wholly unfounded.Nevertheless, (...) this essay attempts to show how misguided this traditional criticism of White actually is. For it is historians who too easily take the truth of their accounts of the past for granted, whereas White's theoretical writings can be shown to express a full awareness of the kind of problem encountered in the effort to tell the truth about historical reality. Hence, White's writings-rather than those by historians criticizing White-testify to the respect that we owe to historical reality itself. That this is how we should read White becomes clear if we consider his intellectual evolution as a whole rather than the individual books or essays that he wrote. (shrink)

In a lengthy article E. Scerri and J. Worrall put forward the case for a novel ‘accommodationist’ version of the events surrounding the development of Mendeleef's Periodic Table 1869–1899. However these authors lay undue stress on the fact that President of the Royal Society of London Spottiswoode made absolutely no mention of Mendeleef's famous predictions in the Davy Medal eulogy in 1883 and undue stress on the fact that Cleve's classic 1879 Scandium paper contained an acknowledgement of Mendeleef's prior prediction (...) of eka-boron.They also fail to analyse in any detail the so-called ‘rare earth problem’ which, in the opinion of this author, causes problems for their account but not for a predictivist account. (shrink)

This title, first published in 1943, aims to discover and discuss the convictions which the philosopher Thomas Carlyle believed to be of importance for his time, and the ways in which he personally entertained these ideas. In doing this F. A. Lea has concentrated attention on the works which Carlyle himself regarded as containing all that was essential to his message. This title will be of interest to students of philosophy and history.

Pickering & Garrod (P&G) put forward the interesting idea that language production relies on forward modeling operating at multiple processing levels. The evidence currently available to substantiate this idea mostly concerns sensorimotor processes and not more abstract linguistic levels (e.g., syntax, semantics, phonology). The predictions that follow from the claim seem too general, in their current form, to guide specific empirical tests.