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)

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

This long-awaited book replaces Hughes and Cresswell's two classic studies of modal logic: _An Introduction to Modal Logic_ and _A Companion to Modal Logic_. _A New Introduction to Modal Logic_ is an entirely new work, completely re-written by the authors. They have incorporated all the new developments that have taken place since 1968 in both modal propositional logic and modal predicate logic, without sacrificing tha clarity of exposition and approachability that were essential features of their earlier works. The book takes (...) readers from the most basic systems of modal propositional logic right up to systems of modal predicate with identity. It covers both technical developments such as completeness and incompleteness, and finite and infinite models, and their philosophical applications, especially in the area of modal predicate logic. (shrink)

Expressions in a language, whether words, phrases, or sentences, have meanings. So it seems reasonable to suppose that there are meanings that expressions have. Of course, it is fashionable in some philosophical circles to deny this.

Martin Heidegger (1889-1976) is probably the most divisive philosopher of the twentieth century. He is considered by some to be greatest charlatan ever to claim the title of philosopher, an apologist for Nazism by others, and an acknowledged leader and central figure to many philosophers. Michael Inwood's lucid introduction steers a clear path through Heidegger's complex language and thought. This short, accessible guide to the existentialist thought of Heidegger focuses on his most important work, Being and Time, and its major (...) themes of existence in the world, inauthenticity, guilt, destiny, truth, and the nature of time. These themes are then reassessed in the light of Heideggers later work, together with the extent of his philosophical importance and influence. For anyone interested in philosophy, theology and literary theory, Heidegger is an invaluable guide to the complex and voluminous thought of a major twentieth-century existentialist philosopher. (shrink)

' I heartily recommend it to any philosopher of language interested in the issues. [] Logicians, of course, will want to savour the whole thing.' Australian Journal of Philosophy, 71:3 (1993).

Liturgy and ritual -- Structure -- Curriculum.

Semantic Indexicality shows how a simple syntax can be combined with a propositional language at the level of logical analysis. It is the adoption of such a base language which has not been attempted before, and it is this which constitutes the originality of the book. Cresswell's simple and direct style makes this book accessible to a wider audience than the somewhat specialized subject matter might initially suggest.

Adverbial modification is probably one of the least understood areas of linguistics. The essays in this volume all address the problem of how to give an analysis of adverbial modifiers within truth-conditional semantics. Chapters I-VI provide analyses of particular modifiers within a possible worlds framework, and were written between 1974 and 1981. Original publication details of these chapters may be found on p. vi. Of these, all but Chapter I make essential use of the idea that the time reference involved (...) in tensed sentences should be a time interval rather than a single instant. The final chapter (Chapter VII) was written especially for this volume and investigates the question of how the 'situation semantics' recently devised by Jon Barwise and John Perry, as a rival to possible-worlds semantics, might deal with adverbs. In addition I have included an appendix to Chapter III and an introduction which links all the chapters together. (shrink)

Over a longer period than I sometimes care to contemplate I have worked on possible-worlds semantics. The earliest work was in modal logic, to which I keep returning, but a sabbatical in 1970 took me to UCLA, there to discover the work of Richard Montague in applying possible-worlds semantics to natural lan guage. My own version of this appeared in Cresswell (1973) and was followed up in a number of articles, most of which were collected in Cresswell (1985b). A central (...) problem for possible worlds semantics is how to accommodate propositional attitudes. This problem was addressed in Cresswell (1985a), and the three books mentioned so far represent a reasonably complete picture of my positive views on formal semantics. I have regarded the presentation of a positive view as more important than the criticism of alternatives, although the works referred to do contain many passages in which I have tried to defend my own views against those of others. But such criticism is important in that a crucial element in establishing the content of a theory is that we be able to evaluate it in relation to its com petitors. It is for that reason that I have collected in this volume a number of articles in which I attempt to defend the positive semantical picture I favour against objections and competing theories. (shrink)

The paper considers the question of when the operator L of necessity in modal logic can be expressed in terms of the operator meaning it is non-contingent that.

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.