Measuring the scattering coefficient of turbid media from two-photon microscopy

International audienceIn this paper, we propose a new and simple method based on two-photon excitation fluorescence (TPEF) microscopy to measure the scattering coefficient μs of thick turbid media. We show, from Monte Carlo simulations, that μs can be derived from the axial profile of the ratio of the TPEF signals epi-collected by the confocal and the non-descanned ports of a scanning microscope, independently of the anisotropy factor g and of the absorption coefficient μa of the medium. The method is validated experimentally on tissue-mimicking optical phantoms, and is shown to have potential for imaging the scattering coefficient of heterogeneous medi

Synthèse d'inhibiteurs du canal potassique SK3 - composés à visée antimétastatique et vectorisation d'ARN interférents

The occurrence of metastasis in a cancer is generally associated to a bad prognostic for the patient. The formation of metastasis is the result of a complex process in which cell migration plays a key role.Recent studies have shown that the potassium calcium-dependent channel SK3 is expressed in several highly metastatic cancerous cell lines and play a direct role in the migration process. Consequently, this protein is an interesting new therapeutic target to reduce metastasis formation.This PhD thesis work aimed investigating two strategies to reduce SK3 dependent cell migration.Edelfosine, a glycerolipid with a phosphocholine head, was identified as an efficient inhibitor of the SK3 channel activity. However the side effects induced by this molecule (toxicity) led to look for efficient and less toxic analogues. Accordingly, structure-activity studies carried out in our laboratory produced new glyco-glycerolipid including one with a lactose group (ohmline). With the aim of completing this study, we report the synthesis of glyco-glycerolipids and glycophospho-glycerolipids and shown their capacity to inhibit activity of SK3 channel.The second part of this work aims to act at an early stage by using RNAi to block the expression of the SK3 protein. In this way, we have synthesized and formulated, with a cationic lipid used for the transfection, neutral co-lipids functionalized with an anisamide moiety; this motif being recognize sigma receptors which are overexpressed in tumor cell lines that also expressed SK3. First, the synthesis of the lipophosphoramides with an anisamide moiety was described followed by their use in standard transfection experiments (plasmid DNA) to evaluate the effectiveness of the targeting strategy induced by the anisamide moiety.L’apparition de métastases est souvent le signe d’un mauvais pronostic vital pour les personnes atteintes d’un cancer. Ce processus de formation de métastase est un phénomène complexe dans lequel la migration cellulaire est un facteur clé.De récentes études ont montré que le canal SK3 (canal potassique de faible conductance dont l’activité dépend de la concentration cytosolique en calcium) était exprimé dans des cellules cancéreuses à fort pouvoir métastatique et leur conférait des capacités de migration accrues. Cette protéine constitue donc une nouvelle cible thérapeutique très intéressante pour agir sur la dissémination de cellules cancéreuses.Les objectifs de ces travaux de thèse ont permis de mettre en oeuvre deux stratégies visant à inhiber l’activité de ce canal potassique SK3.L’édelfosine, un glycérolipide à tête phosphocholine, a rapidement été reconnue comme étant un inhibiteur efficace de l’activité de ce canal. Cependant les effets secondaires induits par cette molécule ont conduit à rechercher des analogues moins toxiques et tout aussi efficaces. Des études structures-activité menées au sein du laboratoire ont permis de développer un nouveau glycérolipide à tête lactose, l’ohmline. Dans le but de compléter cette étude, nous avons réalisé la synthèse de glyco-glycérolipides et de glycophospho-glycérolipides et avons montré leur capacité à inhiber la protéine SK3 et à réduire la migration cellulaire SK3 dépendante.Une seconde stratégie vise à l’utilisation possible d’ARN interférents pour bloquer l’expression de la protéine SK3. Dans ce but, nous nous sommes intéressés à la synthèse et à l’incorporation, dans des formulations de lipides cationiques utilisés pour la transfection, de lipides neutres portant des motifs anisamides, ligands spécifiques des récepteurs sigma surexprimés dans des lignées cellulaires de tumeurs exprimant SK3. La synthèse de lipophosphoramides comportant un motif anisamide est présentée suivie de leur utilisation dans des expériences de transfection modèles (vectorisation d’ADN plasmidique) afin d’évaluer l’efficacité du ciblage engendré par le motif anisamide

Étude biomécanique des mécanismes de progression du spondylolisthésis.

RÉSUMÉ Le spondylolisthésis se définit par un glissement postéro-antérieur d’une vertèbre par rapport à sa sous-jacente. Cette pathologie se développe dans la plupart des cas après une spondylolyse, soit une rupture de la pars interarticulaire de la vertèbre, ou d’une dysplasie importante de ses éléments postérieurs. Le spondylolisthésis affecte environ 6% de la population et apparaît le plus souvent à la jonction lombosacrée (L5-S1). Dans la littérature, on identifie plusieurs sévérités de spondylolisthésis : les spondylolisthésis bas grade (grades 1 et 2), qui comprennent entre autres les types « shear » et « nutcracker », qui se différencient suivant les valeurs de l’incidence pelvienne (PI) et de la pente sacrée (SS) et les spondylolisthésis haut grade (grades 3 à 5) comprenant les types « bassin balancé » et « bassin rétroversé » qui se différencient suivant les valeurs de la pente sacrée et du tilt pelvien (PT). Dans la littérature, la progression du spondylolisthésis est habituellement documentée et analysée au moyen de mesures géométriques (incidence pelvienne, pente sacrée, tilt pelvien) sans prendre en considération leurs effets et leurs actions biomécaniques sur cette progression. C’est pourquoi les relations entre paramètres et forces en jeu dans le risque de progression de la pathologie ne sont pas bien connues. Ainsi, le but du projet était de développer un modèle par éléments finis (MEF) paramétrable d’un rachis----------ABSTRACT Spondylolisthesis is a postero-anterior slippage of a vertebra with respect to its inferior vertebra. This pathology mainly occurs after a spondylolysis, which is a stress fracture of the pars interarticularis of the vertebrae, or after a high dysplasia of its posterior bony elements. Spondylolisthesis affects about 6% of the population and usually occurs at the lumbosacral junction (L5-S1). There exists different severities of spondylolisthesis: lowgrade spondylolisthesis (grades 1 and 2), including the “shear-type” and “nutcrackertype”, which differ in pelvic incidence (PI) and sacral slope (SS) values, and high-grade spondylolisthesis (grade 3 to 5), including “balanced pelvis”-type and “retroverted pelvis”-type, which differ in sacral slope and pelvic tilt (PT) values. The progression of spondylolisthesis is usually documented and analyzed using geometric measurements (PI, SS, PT) without taking their effects and their biomechanical actions into account. That is why the link between the predicting parameters and the forces responsible for the progression of the pathology is poorly documented in the literature. The aim of this project was to develop a parametric finite element model (FEM) of a paediatric spine to analyze the conditions involved in the risk of progression of the pathology and to test the hypothesis that pelvic incidence is a predictive parameter of the deformity. This model includes the spondylolysis and sacral dome, and can be personalized depending on the type of spondylolisthesis. A detailed biomechanica

Antoine Compagnon, Les Cinq paradoxes de la modernité

Les concepts de « moderne », « modernité » et « modernisme » ont été l’objet de nombreux travaux critiques dans les domaines français et anglo-saxons au cours de ces dernières décennies. Les définitions et lectures, parfois convergentes ou conflictuelles, de ces catégories dévoilent les ambiguïtés théoriques qui ont traversé l’histoire récente des beaux-arts. Dans Les Cinq paradoxes de la modernité, Antoine Compagnon propose un panorama critique des divers processus de modélisation artistique..

A nonlinear method of removing harmonic noise in geophysical data

A nonlinear, adaptive method to remove the harmonic noise that commonly resides in geophysical data is proposed in this study. This filtering method is based on the ensemble empirical mode decomposition algorithm in conjunction with the logarithmic transform. We present a synthetic model study to investigate the capability of signal reconstruction from the decomposed data, and compare the results with those derived from other 2-D adaptive filters. Applications to the real seismic data acquired by using an ocean bottom seismograph and to a shot gather of the ground penetrating radar demonstrate the robustness of this method. Our work proposes a concept that instead of Fourier-based approaches, the harmonic noise removal in geophysical data can be achieved effectively by using an alternative nonlinear adaptive data analysis method, which has been applied extensively in other scientific studies

Capturing transition features around a wing by reduced-order modeling based on compressible Navier-Stokes equations

The three-dimensional transition in the flow around a NACA0012 wing of constant spanwise section at Mach number 0.3, Reynolds number 800, and incidence 20° is investigated by direct numerical simulation and reduced-order modeling. The interaction between the von Kármán and the secondary instabilities is analyzed. Irregular events in the flow transition modulating the spanwise undulation are highlighted and quantified. These transition features, including "local intermittencies" in the secondary instability pattern, are efficiently captured by a reduced-order model derived by means of the Galerkin projection of the compressible flow Navier-Stokes equations onto a truncated proper orthogonal decomposition basis

A Perspective on the Use of NB-UVB Phototherapy vs. PUVA Photochemotherapy

Narrowband UVB (NB-UVB) phototherapy and psoralen-UVA (PUVA) photochemotherapy are widely used phototherapeutic modalities for a range of skin diseases. The main indication for NB-UVB and PUVA therapies is psoriasis, and other key diagnoses include atopic eczema, vitiligo, cutaneous T-cell lymphoma (CTCL), and the photodermatoses. The decision on choice of phototherapy is important and NB-UVB is usually the primary choice. NB-UVB phototherapy is a safe and effective therapy which is usually considered when topical agents have failed. PUVA requires prior psoralen sensitization but remains a highly effective mainstay therapy, often used when NB-UVB fails, there is rapid relapse following NB-UVB or in specific indications, such as pustular or erythrodermic psoriasis. This review will provide a perspective on the main indications for use of NB-UVB and PUVA therapies and provide comparative information on these important dermatological treatments

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Mechanistic insight into heptosyltransferase inhibition using Kdo multivalent glycoclusters

peer reviewe

Antithrombin-III Mitigates Thrombin-Mediated Endothelial Cell Contraction and Sickle Red Blood Cell Adhesion in Microscale Flow

Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII pretreatment. Blood samples from subjects with normal haemoglobin (HbAA) and subjects with homozygous SCD (HbSS) were used to examine RBC adhesion to ECs. Endothelial cell surface adhesion molecule expression and confluency in response to thrombin and ATIII treatments were also evaluated. We found that ATIII pretreatment of ECs reduced HbSS RBC adhesion to thrombin-activated endothelium. Furthermore, ATIII mitigated cellular contraction and reduced surface expression of von Willebrand factor and vascular cell adhesion molecule-1 (VCAM-1) mediated by thrombin. Our findings suggest that, by attenuating thrombin-mediated EC damage and RBC adhesion to endothelium, ATIII may alleviate the thromboinflammatory manifestations of SCD