70 research outputs found

    Dense flag triangulations of 3-manifolds via extremal graph theory

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    We characterize f-vectors of sufficiently large three-dimensional flag Gorenstein* complexes, essentially confirming a conjecture of Gal [Discrete Comput. Geom., 34 (2), 269--284, 2005]. In particular, this characterizes f-vectors of large flag triangulations of the 3-sphere. Actually, our main result is more general and describes the structure of closed flag 3-manifolds which have many edges. Looking at the 1-skeleta of these manifolds we reduce the problem to a certain question in extremal graph theory. We then resolve this question by employing the Supersaturation Theorem of Erdos and Simonovits.Comment: Trans. AMS, to appea

    Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases

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    The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance

    Croyances et normes

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    Nous est-il permis de croire que le soleil se lèvera demain? Le fait qu'il se soit levé hier n'est pas suffisant pour en déduire qu'il se lèvera demain. Mais notre intuition nous pousse à le croire. Autrement, l'achat des pains au chocolat pour le petit-déjeuner de demain semblerait être une action prématurée. Alors, que devrait-on croire ? Autrement dit, quelles sont les normes qui gèrent les croyances et leur formation? Lorsque l'on analyse les normes concernant les croyances, deux questions se posent: i) Quel est le lien entre la volonté d'un sujet (l'agent épistémique ou moral) et ses croyances? ii) Quelle est la relation entre les normes et nos intuitions sur les croyances

    Pour en finir avec Mickey

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    Il y a bien longtemps vivait un empereur qui aimait par-dessus tout être bien habillé. Ce dernier avait un habit pour chaque heure de la journée. Un jour, deux escrocs arrivèrent dans la grande ville de l’empereur. Ils prétendirent avoir une étoffe possédant un mode d'être que seules les personnes sottes et les sémanticiens californiens ne pouvaient pas concevoir. L’empereur pensa qu’il y avait là de quoi faire un habit exceptionnel et leur demanda aussitôt de se mettre au travail. Quelques jours plus tard, curieux, il vint voir où les deux compères en étaient avec ce fameux tissu. Il ne vit rien car il n’y avait rien. Les charlatans expliquèrent que l’habit était bien là, mais qu’il n’existait pas. L’empereur ne comprit pas. Troublé, il décida de n’en parler à personne, car personne ne voulait d’un empereur sot. Il envoya plusieurs ministres inspecter l’avancement des travaux. Ils ne comprirent pas plus que le souverain, mais n’osèrent pas non plus l’avouer, de peur de passer pour des imbéciles. Certains disaient que l’habit était et n’existait pas. Les plus érudits disaient qu’à ce dernier manquait totalement l’être, mais qu’il était sujet de prédication: il était en effet très joli, léger, élégant etc. Un sage expliqua qu’on ne pouvait pas le voir parce qu’il n’entrait pas dans des relations causales. Tout le royaume parlait de cette étoffe extraordinaire. Le jour où les deux escrocs décidèrent que l’habit était achevé, ils aidèrent l’empereur à l’enfiler. Ainsi «vêtu» et accompagné de ses ministres, le souverain se présenta à son peuple qui, lui aussi, prétendit voir et admirer ses vêtements. Un sujet cria que l’habit lui «obtenait» à merveille. Seul un petit garçon osa dire la vérité: « Mais il n’a pas d’habit du tout ! ». L’empereur comprit qu’il avait raison, mais continua sa marche sans dire un mot

    Interview: Bas van Fraassen

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    Bas Van Fraassen is a nifty philosopher of science. He received his PhD in Pittsburgh in 1966, under the guidance of Adolf GrĂĽnbaum, he taught at Yale University, the university of Toronto, the University of Southern California, he has been McCosh Professor of Philosophy in Princeton, and eventually joined the department of philosophy at San Francisco State University, where he has the title of Distinguished Professor of Philosophy. He first gained attention with his book An Introduction to the Philosophy of Time and Space where he tried to develop a formal theory of space and time based on the notion of causality. The book had an enormous legacy, with experts of the likes of John Earman and David Malament joining the debate. However, he achieved V.I.P. status with his classic The Scientific Image, where he defends a combination of empiricism and antirealism towards unobservable entities based on a re-definition of what the scientific enterprise is. His last achievement is the tome Scientific Representation: Paradoxes of Perspectives, where he combines his scientific empiricism with the view that theories are best thought as models or structures, rather than sets of sentences. In this interview, we talk about his philosophical influences and the birth of The Scientific Image during a journey through North-Africa, Turkey and Eastern Europe, we talk about saving the phenomena and suspending judgement over the existence of unobservable entities, living in world full of mysteries and leaving unanswerable questions unanswered, rationality and irrationality, living in a simulation, the historical interplay between theorizing and experimenting, the meaning of particle detectors for an empiricist, the unity of science and physicalism, the condemnation of Galilei by the Church, and the distinction between Appearance and Reality

    Aurora Kinase A Is Not Involved in CPEB1 Phosphorylation and <i>cyclin B1</i> mRNA Polyadenylation during Meiotic Maturation of Porcine Oocytes

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    <div><p>Regulation of mRNA translation by cytoplasmic polyadenylation is known to be important for oocyte maturation and further development. This process is generally controlled by phosphorylation of cytoplasmic polyadenylation element binding protein 1 (CPEB1). The aim of this study is to determine the role of Aurora kinase A in CPEB1 phosphorylation and the consequent CPEB1-dependent polyadenylation of maternal mRNAs during mammalian oocyte meiosis. For this purpose, we specifically inhibited Aurora kinase A with MLN8237 during meiotic maturation of porcine oocytes. Using poly(A)-test PCR method, we monitored the effect of Aurora kinase A inhibition on poly(A)-tail extension of long and short cyclin B1 encoding mRNAs as markers of CPEB1-dependent cytoplasmic polyadenylation. Our results show that inhibition of Aurora kinase A activity impairs neither <i>cyclin B1</i> mRNA polyadenylation nor its translation and that Aurora kinase A is unlikely to be involved in CPEB1 activating phosphorylation.</p></div

    Translation of luciferase reporter with <i>cyclin B1</i> 3′UTR in the presence or absence of MLN8237.

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    <p>(A) Schematic representation of porcine and murine <i>cyclin B1</i> 3′UTRs. ORF – open reading frame; CPE – cytoplasmic polyadenylation element; HEX – hexanucleotide, polyadenylation signal; PBE – Pumilio binding element. (B) A non-polyadenylated cRNA containing firefly luciferase open reading frame with murine <i>cyclin B1</i> 3′UTR was co-injected with polyadenylated <i>Renilla</i> luciferase cRNA as an internal injection control into GV-stage oocytes. Oocytes were cultivated for 24 and 28 hours in an inhibitor free medium (control) or the medium supplemented with 1 µM MLN8237. The firefly luciferase activity was normalized to the <i>Renilla</i> luciferase activity. The values are represented as means ± SEM. Data were subjected to t-test with Welch's correction. The differences between control and treated groups are not significant, P>0.05.</p

    Morphological aspect of oocytes treated with MLN8237.

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    <p>Representative examples of morphological appearance of oocytes cultivated for 44 µM MLN8237. (A) Oocytes were fixed with ethanol:acetic acid (3:1) and stained by orcein. Sets of chromosomes are marked with arrowheads, a polar body is marked with and arrow. (B) Detail of chromosome configuration visualized by DAPI.</p

    Detection of AURKA (Thr288) phosphorylation.

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    <p>(A) Fluorescent images of AURKA p-Thr288 localization detected by specific antibody in the GV- and MI-stage oocytes (28 h of IVM) and the oocytes cultivated for 28 h in the presence of 1 µM MLN8237. DNA is stained by DAPI. (B) A detail of chromosomes stained by AURKA p-Thr288 antibody in control MI-stage oocytes (28 h of IVM) and oocytes cultured for 28 h in medium supplemented with 1 µM MLN8237. Representative images from two independent experiments.</p
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