Mining XML Documents

XML documents are becoming ubiquitous because of their rich and flexible format that can be used for a variety of applications. Giving the increasing size of XML collections as information sources, mining techniques that traditionally exist for text collections or databases need to be adapted and new methods to be invented to exploit the particular structure of XML documents. Basically XML documents can be seen as trees, which are well known to be complex structures. This chapter describes various ways of using and simplifying this tree structure to model documents and support efficient mining algorithms. We focus on three mining tasks: classification and clustering which are standard for text collections; discovering of frequent tree structure which is especially important for heterogeneous collection. This chapter presents some recent approaches and algorithms to support these tasks together with experimental evaluation on a variety of large XML collections

Implication of Melanopsin and Trigeminal Neural Pathways in Blue Light Photosensitivity in vivo

Photophobia may arise from various causes and frequently accompanies numerous ocular diseases. In modern highly illuminated world, complaints about greater photosensitivity to blue light increasingly appear. However, the pathophysiology of photophobia is still debated. In the present work, we investigated in vivo the role of various neural pathways potentially implicated in blue-light aversion. Moreover, we studied the light-induced neuroinflammatory processes on the ocular surface and in the trigeminal pathways. Adult male C57BL/6J mice were exposed either to blue (400–500 nm) or to yellow (530–710 nm) LED light (3 h, 6 mW/cm2). Photosensitivity was measured as the time spent in dark or illuminated parts of the cage. Pharmacological treatments were applied: topical instillation of atropine, pilocarpine or oxybuprocaine, intravitreal injection of lidocaine, norepinephrine or “blocker” of the visual photoreceptor transmission, and intraperitoneal injection of a melanopsin antagonist. Clinical evaluations (ocular surface state, corneal mechanical sensitivity and tear quantity) were performed directly after exposure to light and after 3 days of recovery in standard light conditions. Trigeminal ganglia (TGs), brainstems and retinas were dissected out and conditioned for analyses. Mice demonstrated strong aversion to blue but not to yellow light. The only drug that significantly decreased the blue-light aversion was the intraperitoneally injected melanopsin antagonist. After blue-light exposure, dry-eye-related inflammatory signs were observed, notably after 3 days of recovery. In the retina, we observed the increased immunoreactivity for GFAP, ATF3, and Iba1; these data were corroborated by RT-qPCR. Moreover, retinal visual and non-visual photopigments distribution was altered. In the trigeminal pathway, we detected the increased mRNA expression of cFOS and ATF3 as well as alterations in cytokines’ levels. Thus, the wavelength-dependent light aversion was mainly mediated by melanopsin-containing cells, most likely in the retina. Other potential pathways of light reception were also discussed. The phototoxic message was transmitted to the trigeminal system, inducing both inflammation at the ocular surface and stress in the retina. Further investigations of retina-TG connections are needed

CXCR3 Antagonism of SDF-1(5-67) Restores Trabecular Function and Prevents Retinal Neurodegeneration in a Rat Model of Ocular Hypertension

Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration

Rôle des chimiokines CXCL12 et CXCL1 dans la physiopathologie du trabéculum et de la surface oculaire au cours du glaucome

Glaucoma is the first cause of irreversible blindness in the world. Primary open-angle glaucoma (POAG) mostly combines retinal neuropathy with abnormal elevation of the intraocualar pressure, which is the first risk factor for the disease. Ocular hypertension is caused by a trabecular meshwork degeneration whose primary mecanisms are still unknown. Indeed, the current antiglaucoma treatment does not target the intial trabecular pathology so it is not currative. Moreover, antiglaucoma eye drops often contain a preservative, such as benzalkonium chloride (BAC), which has been demonstrated to cause ocular surface inflammation in glaucomatous patients treated over a long term period. Chemokines, small proteins from the cytokine family, have been first described for their chemotactic properties for leukocytes through their interaction with G protein coupled receptors. Aside from its immune properties, the chemokine CXCL12 is involved in the regulation of cell viability and extracellulare matrix remodelling through its receptor CXCR4. Recently, it has been reported that proteolytic cleavage of CXCL12 yields a proapoptotic form, SDF-1(5-67), acting via another chemokine receptor :CXCR3. In this thesis, CXCL12, CXCR3 and CXCR4 have been detected in trabecular cells in human glaucomatous trabecular tissue and immortalized cell line. We originally describe a balance between the protective system CXCL12/CXCR4 and SDF-1(5-67)/CXCR3 which induces trabecular apoptosis under the control of cytokines and matrix metalloproteinases known to be involved in POAG. We report the sucessful use in vivo of a non-peptide specific antagonist of CXCR3 in reducing ocular hypertension and restoring trabecular function in an animal model of glaucoma, opening up new therapeutic avenues in glaucoma. We also studied the role of another chamokine, CX3CL1, in the ocular surface inflammation induced by BAC. CX3CL1 is charaterized by powerful chemoattract properties on CX3CR1-bearing leukocytes. In this study, we report an overexpression of CX3CL1 in conjunctival epithelial cells in glaucomatous patients treated with a BAC-containing medication. In vitro, we demonstrate that BAC-stimulated conjunctival epithelial cells attract lymphocytic and monocytic subpopulations by producing CX3CL1. In an animal model of BAC-induced ocular toxicity, we report a decrease in macrophage infiltration to the conjunctiva in CX3CR1-deficient mice compared to wild-type animals, further confirming that CX3CL1/CX3CR1 is involved in immune cell trafincking in the ocular surface. Our results originally show that chemokines are involved in the pathophysiology of the anterior segment in glaucoma. Chemokines appear as a new regulating system for the pathogenesis of trabecular degeneration in glaucoma as well as for ocular surface inflammation, and could constitute new specific therapeutic targets in such deleterious diseasesLe glaucome primitif à angle ouvert est une neuropathie optique rétinienne dont le premier facteur de risque, l'hypertonie intraoculaire, est causé par une dégénérescence du trabéculum dont les mécanismes demeurent inconnus. Ainsi, les traitements actuels ne ciblent pas la trabéculopathie originelle, ce qui pourrait expliquer leur inefficacité parfois observée. En outre, ces traitements contiennent un conservateur, le chlorure de benzalkonium (BAC), qui est responsable d'une inflammation iatrogène de la surface oculaire mise en cause dans l'inobservance thérapeutique. Les chimiokines, cytokines initialement décrites du fait de leurs propriétés chimioattractantes, sont également impliquées dans le contrôle de la viabilité cellulaire et du microenvironnement tissulaire. Dans cette thèse, nous démontrons l'existence d'une balance au niveau trabéculaire entre le système CXCL12/CXCR4 aux effets protecteurs et le système SDF-1(5-67)/CXCR3 proapoptotique. Nous rapportons de façon originale que l'utilisation in vivo d'un antagoniste non-peptidique spécifique de CXCR3 diminue la pression intraoculaire en restaurant la fonction trabéculaire dans un modèle animal de glaucome. En parallèle, nous révélons que les cellules épithéliales conjonctivales exposées au BAC attirent certaines populations leucocytaires via CX3CL1/CX3CR1, montrant ainsi que ce système est impliqué dans le trafic immunitaire au sein de la surface oculaire. De façon originale, les chimiokines apparaissent comme un système inédit de régulation de l'environnement trabéculaire et de la surface oculaire, constituant ainsi de nouvelles cibles thérapeutiques spécifique

Influence of the Corneal Incision Size on Corneal and Ocular Higher-Order Aberrations After Cataract Surgery: Microincision versus Small-Incision

International audienceno abstrac

Apport de la reconnaissance irienne dans le traitement de l'astigmatisme, des aberrations d'ordre supérieur et sur la qualité de vision après traitement photoablatif personnalisé au laser excimer

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Influences des aberrations sphériques et des autres aberrations optiques d'ordre élevé sur la profondeur de champ du pseudophake (implants asphériques versus implants sphériques)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rôle des chimiokines CXCL12 et CXCL1 dans la physiopathologie du trabéculum et de la surface oculaire au cours du glaucome

Le glaucome primitif à angle ouvert est une neuropathie optique rétinienne dont le premier facteur de risque, l hypertonie intraoculaire, est causé par une dégénérescence du trabéculum dont les mécanismes demeurent inconnus. Ainsi, les traitements actuels ne ciblent pas la trabéculopathie originelle, ce qui pourrait expliquer leur inefficacité parfois observée. En outre, ces traitements contiennent un conservateur, le chlorure de benzalkonium (BAC), qui est responsable d une inflammation iatrogène de la surface oculaire mise en cause dans l inobservance thérapeutique. Les chimiokines, cytokines initialement décrites du fait de leurs propriétés chimioattractantes, sont également impliquées dans le contrôle de la viabilité cellulaire et du microenvironnement tissulaire. Dans cette thèse, nous démontrons l existence d une balance au niveau trabéculaire entre le système CXCL12/CXCR4 aux effets protecteurs et le système SDF-1(5-67)/CXCR3 proapoptotique. Nous rapportons de façon originale que l utilisation in vivo d un antagoniste non-peptidique spécifique de CXCR3 diminue la pression intraoculaire en restaurant la fonction trabéculaire dans un modèle animal de glaucome. En parallèle, nous révélons que les cellules épithéliales conjonctivales exposées au BAC attirent certaines populations leucocytaires via CX3CL1/CX3CR1, montrant ainsi que ce système est impliqué dans le trafic immunitaire au sein de la surface oculaire. De façon originale, les chimiokines apparaissent comme un système inédit de régulation de l environnement trabéculaire et de la surface oculaire, constituant ainsi de nouvelles cibles thérapeutiques spécifiquesGlaucoma is the first cause of irreversible blindness in the world. Primary open-angle glaucoma (POAG) mostly combines retinal neuropathy with abnormal elevation of the intraocualar pressure, which is the first risk factor for the disease. Ocular hypertension is caused by a trabecular meshwork degeneration whose primary mecanisms are still unknown. Indeed, the current antiglaucoma treatment does not target the intial trabecular pathology so it is not currative. Moreover, antiglaucoma eye drops often contain a preservative, such as benzalkonium chloride (BAC), which has been demonstrated to cause ocular surface inflammation in glaucomatous patients treated over a long term period. Chemokines, small proteins from the cytokine family, have been first described for their chemotactic properties for leukocytes through their interaction with G protein coupled receptors. Aside from its immune properties, the chemokine CXCL12 is involved in the regulation of cell viability and extracellulare matrix remodelling through its receptor CXCR4. Recently, it has been reported that proteolytic cleavage of CXCL12 yields a proapoptotic form, SDF-1(5-67), acting via another chemokine receptor :CXCR3. In this thesis, CXCL12, CXCR3 and CXCR4 have been detected in trabecular cells in human glaucomatous trabecular tissue and immortalized cell line. We originally describe a balance between the protective system CXCL12/CXCR4 and SDF-1(5-67)/CXCR3 which induces trabecular apoptosis under the control of cytokines and matrix metalloproteinases known to be involved in POAG. We report the sucessful use in vivo of a non-peptide specific antagonist of CXCR3 in reducing ocular hypertension and restoring trabecular function in an animal model of glaucoma, opening up new therapeutic avenues in glaucoma. We also studied the role of another chamokine, CX3CL1, in the ocular surface inflammation induced by BAC. CX3CL1 is charaterized by powerful chemoattract properties on CX3CR1-bearing leukocytes. In this study, we report an overexpression of CX3CL1 in conjunctival epithelial cells in glaucomatous patients treated with a BAC-containing medication. In vitro, we demonstrate that BAC-stimulated conjunctival epithelial cells attract lymphocytic and monocytic subpopulations by producing CX3CL1. In an animal model of BAC-induced ocular toxicity, we report a decrease in macrophage infiltration to the conjunctiva in CX3CR1-deficient mice compared to wild-type animals, further confirming that CX3CL1/CX3CR1 is involved in immune cell trafincking in the ocular surface. Our results originally show that chemokines are involved in the pathophysiology of the anterior segment in glaucoma. Chemokines appear as a new regulating system for the pathogenesis of trabecular degeneration in glaucoma as well as for ocular surface inflammation, and could constitute new specific therapeutic targets in such deleterious diseasesPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF