On the pp-supports of a holonomic D\mathcal{D}-module

For a smooth variety $Y$ over a perfect field of positive characteristic, the sheaf $D_Y$ of crystalline differential operators on $Y$ (also called the sheaf of $PD$-differential operators) is known to be an Azumaya algebra over $T^*_{Y'},$ the cotangent space of the Frobenius twist $Y'$ of $Y.$ Thus to a sheaf of modules $M$ over $D_Y$ one can assign a closed subvariety of $T^*_{Y'},$ called the $p$-support, namely the support of $M$ seen as a sheaf on $T^*_{Y'}.$ We study here the family of $p$-supports assigned to the reductions modulo primes $p$ of a holonomic $\mathcal{D}$-module. We prove that the Azumaya algebra of differential operators splits on the regular locus of the $p$-support and that the $p$-support is a Lagrangian subvariety of the cotangent space, for $p$ large enough. The latter was conjectured by Kontsevich. Our approach also provides a new proof of the involutivity of the singular support of a holonomic $\mathcal{D}$-module, by reduction modulo $p.$Comment: The article has been rewritten with much improved exposition as well as some additional results, e.g. Corollary 6.3.1. This is the final version, accepted for publication in Inventiones Mathematica

Surface specific peptide immobilization on radiografted polymers as potential screening assays for antiangiogenic immunotherapy

International audienceAngiogenesis is a key process of cancer development and metastasis. It's inhibition is an important and promising strategy to block tumor growth and invasion. One of these approaches, based on antiangiogenic immunotherapy, is the recognition of a specific region of an angiogenic growth factor, called VEGF-A, by monoclonal antibodies. Thus, we aimed to design a novel assay to screen potential monoclonal antibodies directed against VEGF-A. In a first approach, we chose to perform covalent coupling of angiogenesis active cyclopeptides onto biocompatible thermoplastic transparent PVDF films and to fully characterize the chemical structure, the surface state and the biochemical properties of the synthesized devices. Electron beam radiation created radical sites on PVDF films without adding any toxic chemicals. These primary radicals and some induced peroxides were used as initiators for acrylic acid polymerization. Under our experimental conditions, surface grafting was favoured. Functionalization of PVDF-g-PAA films with peptides via a spacer arm was possible by performing two subsequent coupling reactions. EDC was used as coupling agent. Spacer arm saturation of the film surface was achieved for 25 mol% yield meaning that one spacer arm on four carboxylic acids were covalently bound. Peptide immobilization resulted in binding 10 times less leading to a final 3 mol% yield. Binding densities are governed by their individual space requirements. Each chemical step has been followed by FTIR in ATR mode, NMR using HR MAS technique and XPS. From XPS results, a layer of peptide covered PVDF-g-PAA film surface. The amounts of covalently immobilized peptide were determined using indirect UV spectroscopy on supernatant reaction solution. Yields were correlated with high resolution NMR results. The peptide/antibody recognition validated our system showing the conservation of peptide tridimensional structure with a positive response to specific antibodies. Because of the covalent protein linkage to PVDF films, a simple cleaning with immunoaffinity chromatography buffer allows the films to be reused

Whipple's disease diagnosed during biological treatment for joint disease

Objectives Increased susceptibility to infections is among the main safety concerns raised by biological agents. We describe five cases of Whipple\u27s disease diagnosed during treatment with biological agents. Methods We retrospectively identified five cases of Whipple\u27s disease diagnosed between 2003 and 2009 in patients treated with TNFα antagonists in five French hospitals. Results Five patients (four male; mean age: 50.4 years; range: 38–67) underwent biological therapy according to prior diagnoses of rheumatoid arthritis (n = 2), ankylosing spondylitis (n = 2), or spondyloarthropathy (n = 1). Biological therapy failed to control the disease, which responded to appropriate antibiotics for Whipple\u27s disease. Retrospectively, clinical symptoms before biological therapy were consistent with Whipple\u27s disease. All five patients had favorable outcomes (mean follow-up, 29 months [13–71]). Conclusions Biological therapy probably worsened preexisting Whipple\u27s disease, triggering the visceral disorders. Whipple\u27s disease must be ruled out in patients with joint disease, as patients with this spontaneously fatal condition should not receive immunosuppressive agents

Flexural Fatigue Behavior of Cross-Ply Laminates: An Experimental Approach

Within an experimental approach we describe the mechanical behavior of different resin-epoxy laminates reinforced with cross-ply Kevlar and glass fibers under the conditions of static and cyclic three-point bending. In static tests, we consider the effect of stacking sequence, the thickness of 90°-oriented layers, reinforcement type on the mechanical behavior of laminates under loading and on realization of various damage modes leading to rupture. Cyclic loading studies have been performed in two steps. In the first stage, we inquire into the dependence of the behavior and durability of four glass fiber- reinforced laminate-types on the stacking sequence; the second stage is devoted to studying the dependence of cyclic strength and fatigue behavior of laminates on the reinforcement type. Fatigue tests are carried out in load-control regime for glass and hybrid (Kevlar + glass) fiber laminates. Fatigue curves are constructed in coordinates “stress - number of cycles until fracture” from the criteria corresponding to a drop in stiffness by 5 and 10%. Analysis of the results obtained permits evaluation of the effect of the stacking sequence and the reinforcement type on the behavior of cross-ply laminates in cyclic loading. The presence of Kevlar fibers accounts for nonlinear behavior of laminates in static tests and for low cyclic strength in fatigue tests under three-point bending.В рамках экспериментального подхода описано механическое поведение различных ламинатов с матрицей из эпоксидной смолы, перекрестно-армированных кевларовыми волокнами и стекловолокнами, в условиях статического и циклического трехточечного изгиба. При статических испытаниях рассматриваются последовательность укладки слоев и волокон, толщины слоев, ориентированных под углом 90° и влияние типа армирования на механическое поведение ламинатов в процессе нагружения, а также на реализацию различных режимов повреждения, приводящих к разрушению. Исследования при циклическом нагружении состоят из двух этапов. На первом этапе изучается влияние последовательности укладки слоев и волокон на поведение и долговечность четырех типов ламинатов, армированных стекловолокнами, на втором этапе - влияние типа армирования на циклическую прочность и сопротивление ламинатов при циклическом нагружении. Усталостные испытания выполнены в мягком режиме нагружения для ламинатов, армированных стекловолокнами и гибридными волокнами (кевлар+стекло). Кривые усталости были построены в координатах напряжение - число циклов до разрушения на основе критериев снижения жесткости на 5 и 10%. Анализ полученных результатов позволяет оценить влияние последовательности укладки слоев и типа армирования на поведение перекрестно-армированных ламинатов при циклическом нагружении. Наличие кевларовых волокон в ламинатах обеспечивает их нелинейное поведение при статических испытаниях и низкую циклическую прочность при усталостных испытаниях в условиях трехточечного изгиба.У рамках експериментального підходу описано механічну поведінку різних ламінатів із матрицею з епоксидної смоли, що перехресноармовані кевларо- вими волокнами і скловолокнами, в умовах статичного і циклічного три- точкового згину. При статичних випробуваннях розглядаються послідовність укладення шарів і волокон, товщини орієнтованих під кутом 90° шарів і вплив типу армування на механічну поведінку ламінатів у процесі навантаження, а також на реалізацію різних режимів пошкодження, що призводить до руйнування. Дослідження при циклічному навантаженні складається з двох етапів. На першому етапі розглядається вплив послідовності укладення шарів і волокон на поведінку і довговічність чотирьох типів армованих скловолокнами ламінатів, на другому етапі - вплив типу армування на циклічну міцність і опір ламінатів при циклічному навантаженні. Випробування на втому виконано у м ’якому режимі навантаження для армованих скловолокнами і гібридними волокнами (кевлар + скло) ламінатів. На основі критеріїв зниження жорсткості на 5 і 10% в координатах напруження - число циклів до руйнування побудовано криві утоми. Аналіз отриманих результатів дозволяє оцінити вплив послідовності укладення шарів і типу армування на поведінку перехресноармованих ламінатів при циклічному навантаженні. Наявність кевларових волокон у ламінатах запезчує їх нелінійну поведінку при статичних випробуваннях і низьку циклічну міцність при випробуваннях на втому в умовах триточкового згину

Tunable Indistinguishable Photons From Remote Quantum Dots

Single semiconductor quantum dots have been widely studied within devices that can apply an electric field. In the most common system, the low energy offset between the InGaAs quantum dot and the surrounding GaAs material limits the magnitude of field that can be applied to tens of kVcm^-1, before carriers tunnel out of the dot. The Stark shift experienced by the emission line is typically 1 meV. We report that by embedding the quantum dots in a quantum well heterostructure the vertical field that can be applied is increased by over an order of magnitude whilst preserving the narrow linewidths, high internal quantum efficiencies and familiar emission spectra. Individual dots can then be continuously tuned to the same energy allowing for two-photon interference between remote, independent, quantum dots

Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans

Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses are prolonged leading to a two-fold increase in total charge transfer. The enhanced response in tom-1 mutants is not associated with any detectable changes in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis. However, at the ultrastructural level, we observe a concomitant increase in the number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact nervous system, TOM-1 negatively regulates synaptic vesicle priming. © 2006 Gracheva et al