Special fast diffusion with slow asymptotics. Entropy method and flow on a Riemannian manifold

We consider the asymptotic behaviour of positive solutions $u(t,x)$ of the fast diffusion equation $u_t=\Delta (u^{m}/m)={\rm div} (u^{m-1}\nabla u)$ posed for x\in\RR^d, $t>0$, with a precise value for the exponent $m=(d-4)/(d-2)$. The space dimension is $d\ge 3$ so that $m<1$, and even $m=-1$ for $d=3$. This case had been left open in the general study \cite{BBDGV} since it requires quite different functional analytic methods, due in particular to the absence of a spectral gap for the operator generating the linearized evolution. The linearization of this flow is interpreted here as the heat flow of the Laplace-Beltrami operator of a suitable Riemannian Manifold (\RR^d,{\bf g}), with a metric ${\bf g}$ which is conformal to the standard \RR^d metric. Studying the pointwise heat kernel behaviour allows to prove {suitable Gagliardo-Nirenberg} inequalities associated to the generator. Such inequalities in turn allow to study the nonlinear evolution as well, and to determine its asymptotics, which is identical to the one satisfied by the linearization. In terms of the rescaled representation, which is a nonlinear Fokker--Planck equation, the convergence rate turns out to be polynomial in time. This result is in contrast with the known exponential decay of such representation for all other values of $m$.Comment: 37 page

Topological and geometrical restrictions, free-boundary problems and self-gravitating fluids

Let (P1) be certain elliptic free-boundary problem on a Riemannian manifold (M,g). In this paper we study the restrictions on the topology and geometry of the fibres (the level sets) of the solutions f to (P1). We give a technique based on certain remarkable property of the fibres (the analytic representation property) for going from the initial PDE to a global analytical characterization of the fibres (the equilibrium partition condition). We study this analytical characterization and obtain several topological and geometrical properties that the fibres of the solutions must possess, depending on the topology of M and the metric tensor g. We apply these results to the classical problem in physics of classifying the equilibrium shapes of both Newtonian and relativistic static self-gravitating fluids. We also suggest a relationship with the isometries of a Riemannian manifold.Comment: 36 pages. In this new version the analytic representation hypothesis is proved. Please address all correspondence to D. Peralta-Sala

Oxidised cosmic acceleration

We give detailed proofs of several new no-go theorems for constructing flat four-dimensional accelerating universes from warped dimensional reduction. These new theorems improve upon previous ones by weakening the energy conditions, by including time-dependent compactifications, and by treating accelerated expansion that is not precisely de Sitter. We show that de Sitter expansion violates the higher-dimensional null energy condition (NEC) if the compactification manifold M is one-dimensional, if its intrinsic Ricci scalar R vanishes everywhere, or if R and the warp function satisfy a simple limit condition. If expansion is not de Sitter, we establish threshold equation-of-state parameters w below which accelerated expansion must be transient. Below the threshold w there are bounds on the number of e-foldings of expansion. If M is one-dimensional or R everywhere vanishing, exceeding the bound implies the NEC is violated. If R does not vanish everywhere on M, exceeding the bound implies the strong energy condition (SEC) is violated. Observationally, the w thresholds indicate that experiments with finite resolution in w can cleanly discriminate between different models which satisfy or violate the relevant energy conditions.Comment: v2: corrections, references adde

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

La pathologie articulaire de la cheville

Ostéochondrite de l'astragale; syndrome antérieur de la cheville; syndrome de conflit postérieu

La chirurgie du cartilage chez le sujet sportif

Analyse de différentes techniques de réparation des lésions cartilagineuses localisées non arthrosiques chez le sportif : technique des microfractures, greffes autologues ostéochondrales en mosaïque, greffes de chondrocytes autologues. Limites biologiques et biomécaniques de ces techniques