Traditionally, the impairment of cognitive functions in Alzheimeŕs disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large‐scale networks, with a variety of electrophysiological and imaging techniques have revealed two forms of (...) AD‐related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches. (shrink)

Neurotrophins (NTs) are {?AUTHOR} a family of structurally related, secreted proteins that regulate the survival, differentiation and maintenance of function of different populations of peripheral and central neurons.1,2 Among these, BDNF (brain‐derived neurotrophic factor) has drawn considerable interest because both its synthesis and secretion are increased by physiological levels of activity, indicating a unique role of this neurotrophin in coupling neuronal activity to structural and functional properties of neuronal circuits. In addition to its classical neurotrophic effects, which are evident within (...) hours or days and which usually result from changes in cellular gene expression, BDNF exerts acute effects on synaptic transmission and is involved in the induction of long‐term potentiation. Many of these rapid effects of BDNF are mediated by its modulation of ion channel properties following TrkB‐mediated activation of intracellular second messenger cascades and protein phosphorylation. However, recent reports have shown that BDNF not only acts as a modulator of ion channels, but can also directly and rapidly gate a Na+ channel, thereby assigning BDNF the properties of a classical excitatory transmitter. Thus, BDNF, in addition its role as a potent neuromodulator, emerges as an excitatory transmitter‐like substance which acutely controls resting membrane potential, neuronal excitability, synaptic transmission and participates in the induction of synaptic plasticity. BioEssays 26:1185–1194, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Twentieth-century developments in quantum physics, together with an emerging science of consciousness, have created the need for a new cosmology, or model of the universe. The theory of process contained in THE REFLEXIVE UNIVERSE places consciousness within the context of contemporary science. One of the central themes of this extraordinary work is that each successive organization of matter, from fundamental particles in physics to living organisms, expresses a particular stage in the evolution of mind. Starting with the photon, the basic (...) unit of light, and moving through atomic physics, molecular chemistry, the morphology of plants and animals and finally to levels of human evolution, Young develops his theory in vivid step-by-step detail. Consciousness, in his point of view, is not isolated from the material universe. It exists in a continuum, one in which physical and nonphysical realms can be linked and the teachings of mythology and religion can be integrated. To order: FAX: 415-883-9280; e-mail: [email protected]; or write: Anodos Foundation, c/o Publishers Services, P.O. Box 2510, Novato, CA 94948. Visa and MasterCard only. Trade STOP orders 40% plus postage. (shrink)

Against Norton's claim that all thought experiments can be reduced to explicit arguments, I defend Brown's position that certain thought experiments yield a priori knowledge. They do this, I argue, not by allowing us to perceive “Platonic universals” (Brown), even though they may contain non-propositional components that are epistemically indispensable, but by helping to identify certain tacit presuppositions or “natural interpretations” (Feyerabend's term) that lead to a contradiction when the phenomenon is described in terms of them, and by suggesting a (...) new natural interpretation in terms of which the phenomenon can be redescribed free of contradiction. (shrink)

We examine combinatorial aspects and consistency strength properties of almost Ramsey cardinals. Without the Axiom of Choice, successor cardinals may be almost Ramsey. From fairly mild supercompactness assumptions, we construct a model of ZF + ${\neg {\rm AC}_\omega}$ in which every infinite cardinal is almost Ramsey. Core model arguments show that strong assumptions are necessary. Without successors of singular cardinals, we can weaken this to an equiconsistency of the following theories: “ZFC + There is a proper class of regular almost (...) Ramsey cardinals”, and “ZF + DC + All infinite cardinals except possibly successors of singular cardinals are almost Ramsey”. (shrink)

Let φ1 stand for the statement V = HOD and φ2 stand for the Ground Axiom. Suppose Ti for i = 1, …, 4 are the theories “ZFC + φ1 + φ2,” “ZFC + ¬φ1 + φ2,” “ZFC + φ1 + ¬φ2,” and “ZFC + ¬φ1 + ¬φ2” respectively. We show that if κ is indestructibly supercompact and λ > κ is inaccessible, then for i = 1, …, 4, Ai = df{δ κ is inaccessible. We show it is also (...) the case that if κ is indestructibly supercompact, then Vκ⊨T1, so by reflection, B1 = df{δ κ is inaccessible, we demonstrate that it is possible to construct a model in which κ is indestructibly supercompact and for every inaccessible cardinal δ < κ, Vδ⊨T1. It is thus not possible to prove in ZFC that Bi = df{δ < κ∣δ is an inaccessible limit of inaccessible cardinals and Vδ⊨Ti} for i = 2, …, 4 is unbounded in κ if κ is indestructibly supercompact. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (shrink)

We construct models containing exactly one supercompact cardinal in which level by level inequivalence between strong compactness and supercompactness holds. In each model, above the supercompact cardinal, there are finitely many strongly compact cardinals, and the strongly compact and measurable cardinals precisely coincide.

Suppose that κ is indestructibly supercompact and there is a measurable cardinal λ > κ. It then follows that A1 = {δ < κ∣δ is measurable, δ is not a limit of measurable cardinals, and δ is not δ+ supercompact} is unbounded in κ. If in addition λ is 2λ supercompact, then A2 = {δ < κ∣δ is measurable, δ is not a limit of measurable cardinals, and δ is δ+ supercompact} is unbounded in κ as well. The large cardinal (...) hypotheses on λ are necessary, as we further demonstrate by constructing via forcing two distinct models in which either equation image or equation image. In each of these models, there is an indestructibly supercompact cardinal κ, and a restricted large cardinal structure above κ. If we weaken the indestructibility requirement on κ to indestructibility under partial orderings which are both κ-directed closed and -distributive, then it is possible to construct a model containing a supercompact cardinal κ witnessing this degree of indestructibility in which every measurable cardinal δ < κ is δ+ supercompact. (shrink)

This paper addresses the “inefficiency loophole” in the Bell theorem. We examine factorizable stochastic models for the Bell inequalities, where we allow the detection efficiency to depend both on the “hidden” state of the measured system and also its passage through an analyzer. We show that, nevertheless, if the efficiency functions are symmetric between the two wings of the experiment, one can dispense with supplementary assumptions and derive new inequalities that enable the models to be tested even for highly inefficient (...) experiments. (shrink)

We establish two theorems concerning strongly compact cardinals and universal indestructibility for degrees of supercompactness. In the first theorem, we show that universal indestructibility for degrees of supercompactness in the presence of a strongly compact cardinal is consistent with the existence of a proper class of measurable cardinals. In the second theorem, we show that universal indestructibility for degrees of supercompactness is consistent in the presence of two non-supercompact strongly compact cardinals, each of which exhibits a significant amount of indestructibility (...) for its strong compactness. (shrink)

Excerpt from Kants Naturphilosophie als Grundlage Seines Systems Die vorliegende Arbeit uber die kantische Naturphilosophie war ursprunglich in Aussicht genommen als erstes Kapitel einer Darstellung der deutschen Naturphilosophie seit Kam. Der Grund, warum sie zu einem selbstandigen Werke angeschwollen ist, liegt darin, weil ich bei genauerem Studium des Philosophen fand, man habe das naturphilosophische Element in den Schriften Kants bisher bei weitem unterschatzt und insbesondere seinen Bemuhungen um eine dynamische Theorie der Materie lange nicht diejenige Bedeutung zugeschrieben, die ihnen sowohl (...) in Hinsicht auf die Richtung, welche die kantische Gedankenentwickelung genommen hat, wie fur die eigentumliche Ausbildung dieser Gedanken im Einzelnen thatsachlich beizumessen ist. Man hat den Philosophen nach seiner theoretischen Seite fast lediglich als den Begrunder der modernen Erkenntnistheorie gewurdigt und dabei ubersehen, wie seine ganze Erkenntnistheorie aus naturphilosophischen Erwagungen hervorgegangen und oft in den wichtigsten Punkten von ihnen bestimmt worden ist. Die vorliegende Arbeit schopft nun bei der Hochflut der philosophischen Litteratur, die sich mit Kant beschaftigt, ihre Daseinsberechtigung vor allem daraus, dafs sie die gesamte theoretische Philosophie Kants unter dem Gesichtspunkte der Naturphilosophie betrachtet. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works.". (shrink)

I think it will be agreed that there is a domain of investigation where physics and philosophy overlap. There are branches of philosophy which do not approach the subject-matter of physics, and a great part of the work of practical and theoretical physicists is not aimed at extending our knowledge of the fundamental nature of things; but questions which concern the general interpretation of the physical universe and the significance of physical law are claimed by both parties. I suppose that (...) ideally the physicist should be allowed to elucidate his own universe up to a point, and then hand it over to the philosopher to ascertain its exact status in relation to a wider outlook. (shrink)

Introspection reveals that the core of subjectivity -- the ‘I’ -- is identical to awareness. This ‘I’ should be differentiated from the various aspects of the physical person and its mental contents which form the ‘self’. Most discussions of consciousness confuse the ‘I’ and the ‘self’. In fact, our experience is fundamentally dualistic -- not the dualism of mind and matter -- but that of the ‘I’ and that which is observed. The identity of awareness and the ‘I’ means that (...) we know awareness by being it, thus solving the problem of the infinite regress of observers. It follows that whatever our ontology of awareness may be, it must also be the same for ‘I’. (shrink)

There is a form of intellectual controversy, exhibited throughout the nineteenth century and into our own, which is less accessible because of a radically different order than certain controversies it appears to resemble, namely those which sprang up dramatically between science and religion in this era. Those latter controversies developed chiefly because it was at first supposed that religion was in possession of factual truths which entailed answers incompatible with those offered by science, to just the same factual questions: the (...) age of the universe, the mutability of species, the community of men and beasts or, for the matter, the historicity of sacred writ itself. On the basis of criteria supposed appropriate to the resolution of scientific controversies as such, the factual claims of religion were one by one infirmed, and it seemed then a reasonable projection that more or less the same would happen in any future such collisions. This left certain options open for religionists. They could, like adherents of any infirmed theory, simply give them up like good scientists are supposed to do. Or they could attempt to shun refutation by regarding religious statements as mere mythic paraphrases of recoverable literal scientific statements which were in fact true. Or religion could constitute itself a specialized science, concerned with an area of reality the "other" sciences did not touch upon, purging itself of any statements which then could conflict with those of the "other" sciences. Or finally, it could radically redefine its own scope and office by foreswearing any claim at all to factuality, so that questions of truth or falsity simply no longer would apply, and controversies between it and any discipline to which such questions did apply would be as inconceivable as a truth-contest between chemistry and opera. The Wittgensteinian suggestion that it is not the purpose of religious language to state facts may be seen as a late response to a dilemma which is then resolved by assigning religious utterance to one language game and physics to another. Were this a suitable disposition of the matter, religionists might be grateful for the suffering undergone, for though in the light of it the dilemma need never have arisen, still, had it not done so, religion might never have arrived at a proper consciousness of its own deep character. So the recent history of religion recapitulates its own favorite episodes of trial and purified renascence. (shrink)

We show that from a supercompact cardinal $\kappa$, there is a forcing extension $V[G]$ that has a symmetric inner model $N$ in which $\mathrm {ZF}+\lnot\mathrm {AC}$ holds, $\kappa$ and $\kappa^{+}$ are both singular, and the continuum function at $\kappa$ can be precisely controlled, in the sense that the final model contains a sequence of distinct subsets of $\kappa$ of length equal to any predetermined ordinal. We also show that the above situation can be collapsed to obtain a model of $\mathrm (...) {ZF}+\lnot\mathrm {AC}_{\omega}$ in which either $\aleph_{1}$ and $\aleph_{2}$ are both singular and the continuum function at $\aleph_{1}$ can be precisely controlled, or $\aleph_{\omega}$ and $\aleph_{\omega+1}$ are both singular and the continuum function at $\aleph_{\omega}$ can be precisely controlled. Additionally, we discuss a result in which we separate the lengths of sequences of distinct subsets of consecutive singular cardinals $\kappa$ and $\kappa^{+}$ in a model of $\mathrm {ZF}$. Some open questions concerning the continuum function in models of $\mathrm {ZF}$ with consecutive singular cardinals are posed. (shrink)

There is an obscure passage in a letter from Keats to Benjamin Bailey, written in 1817, which says: I am certain of nothing but of the holiness of the Heart's affections and the truth of Imagination...This does not seem to make much sense. Nor does it help much to find an echo of that passage in the famous last lines of the Ode on a Grecian Urn, written two years later: Beauty is truth, truth beauty — that is all Ye (...) know on earth, and all ye need to know. (shrink)

A construção de modelos artificiais capazes de tomar decisões geralmente é contrastada à fraca estrutura de comportamento ético capaz de compreender o uso de inteligência artificial para a escolha moral. Neste artigo, discutimos o papel da ética de Hans Jonas e da filosofia crítica de Andrew Feenberg na determinação de princípios para uma ética destes modelos, indo na direção oposta às pesquisas e publicações recentes na área. Analisando o caso específico trazido em Boot et al., à luz de ambos filósofos, (...) podemos demonstrar como os avanços na técnica carecem da necessária crítica filosófica e estudo da nova ética na era da tecnologia. (shrink)

We prove two theorems concerning indestructibility properties of the first two strongly compact cardinals when these cardinals are in addition the first two measurable cardinals. Starting from two supercompact cardinals $\kappa _1 < \kappa _2$, we force and construct a model in which $\kappa _1$ and $\kappa _2$ are both the first two strongly compact and first two measurable cardinals, $\kappa _1$ ’s strong compactness is fully indestructible, and $\kappa _2$ ’s strong compactness is indestructible under $\mathrm {Add}$ for any (...) ordinal $\delta $. This provides an answer to a strengthened version of a question of Sargsyan found in [17, Question 5]. We also investigate indestructibility properties that may occur when the first two strongly compact cardinals are not only the first two measurable cardinals, but also exhibit nontrivial degrees of supercompactness. (shrink)

Excerpt from Leçons de Morale Fausses conceptions que l'on a du droit, de la justice et du devoir. La vraie définition du droit, de la justice et du devoir, c'est la morale qui la fournit. Elle seule peut endiguer le flot sans cesse menaçant des doctrines qui sous le couvert d'ordre et de prospérité sont les pires ennemis de la paix et de la tranquilité des nations. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. (...) Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

If κ < λ are such that κ is indestructibly supercompact and λ is measurable, then we show that both A = {δ < κ | δ is a measurable cardinal which is not a limit of measurable cardinals and δ carries the maximal number of normal measures} and B = {δ < κ | δ is a measurable cardinal which is not a limit of measurable cardinals and δ carries fewer than the maximal number of normal measures} are unbounded (...) in κ. The two aforementioned phenomena, however, need not occur in a universe with an indestructibly supercompact cardinal and sufficiently few large cardinals. In particular, we show how to construct a model with an indestructibly supercompact cardinal κ in which if δ < κ is a measurable cardinal which is not a limit of measurable cardinals, then δ must carry fewer than the maximal number of normal measures. We also, however, show how to construct a model with an indestructibly supercompact cardinal κ in which if δ < κ is a measurable cardinal which is not a limit of measurable cardinals, then δ must carry the maximal number of normal measures. If we weaken the requirements on indestructibility, then this last result can be improved to obtain a model with an indestructibly supercompact cardinal κ in which every measurable cardinal δ < κ carries the maximal number of normal measures. (shrink)

Given the personalist's latitudinarian conception of rationality, what is progress toward wisdom? An answer is in C. I. Lewis's concept of the "congruence" of propositions, propositions so related that the antecedent probability of any one of them will be increased if the remainder can be assumed. This effect can be modelled in the probability calculus with due attention to the temporal sequencing of our learning of contingent propositions without ever becoming certain of them, as Jeffrey proposes. A diachronic bootstrapping effect (...) is obtained for Ockham's razor and premises of arguments about a god's existence. As a theory's probability rises with increased evidence, the probability of our earlier evidence rises too. (shrink)

Levelt et al. attempt to “model their theory” with WEAVER ++. Modeling theories requires a model theory. The time is ripe for a methodology for building, testing, and evaluating computational models. We propose a tentative, five-step framework for tackling this problem, within which we discuss the potential strengths and weaknesses of Levelt et al.'s modeling approach.