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This essay explores an alternative pathway to Alzheimer’s dementia that focuses on damage to small blood vessels rather than late-stage toxic amyloid deposits as the primary pathogenic mechanism that leads to irreversible dementia. While the end-stage pathology of AD is well known, the pathogenic processes that lead to disease are often assumed to be due to toxic amyloid peptides that act on neurons, leading to neuronal dysfunction and eventually neuronal cell death. Speculations as to what initiates the pathogenic cascade have included toxic abeta peptide aggregates, oxidative damage, and inflammation, but none explain why neurons die. Recent high-resolution NMR studies of living patients show that lesions in white matter regions of the brain precede the appearance of amyloid deposits and are correlated with damaged small blood vessels. To appreciate the pathogenic potential of damaged small blood vessels in the brain, it is useful to consider the clinical course and the pathogenesis of CADASIL, a heritable arteriopathy that leads to damaged small blood vessels and irreversible dementia. CADASIL is strikingly similar to early onset AD in that it is caused by germ line mutations in NOTCH 3 that generate toxic protein aggregates similar to those attributed to mutant forms of the amyloid precursor protein and presenilin genes. Since NOTCH 3 mutants clearly damage small blood vessels of white matter regions of the brain that lead to dementia, we speculate that both forms of dementia may have a similar pathogenesis, which is to cause ischemic damage by blocking blood flow or by impeding the removal of toxic protein aggregates by retrograde vascular clearance mechanisms.  相似文献   
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Summary The present study demonstrates a powerful vasoconstrictor activity of prostaglandin-like substances (PLS), extracted fromP. acnes, on human blood vessels. PLS is about equipotent to PGE2 in its effect on human umbilical vessels, but the contractile response pattern is different. PLS therefore seems to have specific and different physiological characteristics.  相似文献   
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Summary The phenetic relationships between the families of the Hamamelididae subclass were studied by using the following multifactorial analytical methods: principal components analysis (PCA) and reciprocal averaging (RA). The results obtained agree appreciably with Takhtajan's classification system.

Remerciements. Nous remercions Mlle Sylvie Laliberté, Institut botanique de l'Université de Montréal, pour sa révision du manuscrit; M. Michel Labrecque, Institut botanique de l'Université de Montréal, pour avoir dessiné les figures; de même que M. André Bouchard, Jardin Botanique de Montréal et Institut botanique de l'Université de Montréal, de nous avoir permis d'utiliser les programmes dont il se sert pour ses travaux d'écologie.  相似文献   
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Résumé Certains neurones hypothalamiques présentent dans la demi-heure qui suit une stimulation vaginale des modifications de leur décharge spontanée indépendantes de l'état de vigilance de l'animal. Ces variations pourraient être en rapport avec les mécanismes nerveux de l'ovulation provoquée chez la Lapine.

We are very grateful to Dr. J. N.Hayward, Department of Anatomy, University of California, Los Angeles, for his constructive criticisms.  相似文献   
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The peculiar object P/2010?A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010?A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.  相似文献   
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A k-dissimilarity D on a finite set X, |X|????k, is a map from the set of size k subsets of X to the real numbers. Such maps naturally arise from edgeweighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y ) is defined to be the total length of the smallest subtree of T with leaf-set Y . In case k?=?2, it is well-known that 2-dissimilarities arising in this way can be characterized by the so-called ??4-point condition??. However, in case k?>?2 Pachter and Speyer (2004) recently posed the following question: Given an arbitrary k-dissimilarity, how do we test whether this map comes from a tree? In this paper, we provide an answer to this question, showing that for k????3 a k-dissimilarity on a set X arises from a tree if and only if its restriction to every 2?k-element subset of X arises from some tree, and that 2?k is the least possible subset size to ensure that this is the case. As a corollary, we show that there exists a polynomial-time algorithm to determine when a k-dissimilarity arises from a tree. We also give a 6-point condition for determining when a 3-dissimilarity arises from a tree, that is similar to the aforementioned 4-point condition.  相似文献   
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