The Effect of Dynamical Image Forces on The Transport Properties of Charge Carriers and Excitons in Metal-Semiconductor Nanostructures

We examine coupled metal nanoparticle/semiconductor hybrid nano-stuctures and analyze the effect that the surface response metal nanoparticles (MNP) has on the transport properties of the system. This analysis is accomplished by treating surface plasmons as quantum oscillators. We find that charge carriers traveling in the nearby semiconductors experience a repulsion due to the ground state energy of the quantum SP (QSP). This effect is shown to be the quantum analogue of the ponderomotive effect found in plasma physics. We then extend the theory to examine the transport properties of carbon nano-tube excitons in the presence of localized SPs and show that this system maps onto a Fano-Anderson Hamiltonian. Through numerical simulation, we show that the emission patterns of the system are severely modified by the presence of localized surface plasmons

Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking.

Tunneling nanotubes (TNTs) are cellular extensions enabling cytosol-to-cytosol intercellular interaction between numerous cell types including macrophages. Previous studies of hematopoietic stem and progenitor cell (HSPC) transplantation for the lysosomal storage disorder cystinosis have shown that HSPC-derived macrophages form TNTs to deliver cystinosin-bearing lysosomes to cystinotic cells, leading to tissue preservation. Here, we explored if macrophage polarization to either proinflammatory M1-like M(LPS/IFNγ) or anti-inflammatory M2-like M(IL-4/IL-10) affected TNT-like protrusion formation, intercellular transport and, ultimately, the efficacy of cystinosis prevention. We designed new automated image processing algorithms used to demonstrate that LPS/IFNγ polarization decreased bone marrow-derived macrophages (BMDMs) formation of protrusions, some of which displayed characteristics of TNTs, including cytoskeletal structure, 3D morphology and size. In contrast, co-culture of macrophages with cystinotic fibroblasts yielded more frequent and larger protrusions, as well as increased lysosomal and mitochondrial intercellular trafficking to the diseased fibroblasts. Unexpectedly, we observed normal protrusion formation and therapeutic efficacy following disruption of anti-inflammatory IL-4/IL-10 polarization in vivo by transplantation of HSPCs isolated from the Rac2-/- mouse model. Altogether, we developed unbiased image quantification systems that probe mechanistic aspects of TNT formation and function in vitro, while HSPC transplantation into cystinotic mice provides a complex in vivo disease model. While the differences between polarization cell culture and mouse models exemplify the oversimplicity of in vitro cytokine treatment, they simultaneously demonstrate the utility of our co-culture model which recapitulates the in vivo phenomenon of diseased cystinotic cells stimulating thicker TNT formation and intercellular trafficking from macrophages. Ultimately, we can use both approaches to expand the utility of TNT-like protrusions as a delivery system for regenerative medicine

CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by expansion of GAA repeats in intron 1 of the frataxin (FXN) gene, leading to significant decreased expression of frataxin, a mitochondrial iron-binding protein. We previously reported that syngeneic hematopoietic stem and progenitor cell (HSPC) transplantation prevented neurodegeneration in the FRDA mouse model YG8R. We showed that the mechanism of rescue was mediated by the transfer of the functional frataxin from HSPC-derived microglia/macrophage cells to neurons/myocytes. In this study, we report the first step toward an autologous HSPC transplantation using the CRISPR-Cas9 system for FRDA. We first identified a pair of CRISPR RNAs (crRNAs) that efficiently removes the GAA expansions in human FRDA lymphoblasts, restoring the non-pathologic level of frataxin expression and normalizing mitochondrial activity. We also optimized the gene-editing approach in HSPCs isolated from healthy and FRDA patients' peripheral blood and demonstrated normal hematopoiesis of gene-edited cells in vitro and in vivo. The procedure did not induce cellular toxic effect or major off-target events, but a p53-mediated cell proliferation delay was observed in the gene-edited cells. This study provides the foundation for the clinical translation of autologous transplantation of gene-corrected HSPCs for FRDA

Innovation pédagogique Les apports de la culture et de l’art

Le soutien scolaire est une pratique qui a accompagné, depuis toujours, l’opération d’enseignement apprentissage. Avant les années quatre-vingt, le soutien était généralement institutionnel, dispensé par des professeurs pour leurs propres élèves, au sein de l’établissement scolaire soit durant les heures de cours soit lors de séances réservées à ce type d’activité en se fixant comme objectifs primordiaux, la mise à niveau et la remédiation aux lacunes.Avec l’émergence de l’enseignement privé et l’ampleur qu’il a pris surtout au début des années quatre-vingt-dix, le soutien scolaire a pris d’autres formes et s’est fixé d’autres objectifs.Mais la majorité des enseignants ont recours lors des séances de soutien scolaire aux mêmes méthodes adoptées lors de l’enseignement durant les séances de classe. Or, il faut revoir les méthodes de ces séances et chercher à mettre en place des cours participatifs faisant appel à l’analyse de l’image et la découverte de l’art

Deep learning on graph for semantic segmentation of point cloud

This master thesis provides in-depth explanations of how deep learning and graph theory can be used together to perform pointwise classification in 3D point clouds obtained by combinations of geospatial images. That scene understanding problem arises in a number of practical scenarios, e.g. for governments to survey deforestation from aerial images taken by drones. After an introduction on the problem statement and the main assets of typical architectures used for images, this thesis introduces the neural network architecture we developed, and describes how to build its main elements together with the graphs. To assess its performances, our architecture based on graph convolutions was tested under two different scenarios and compared to traditional machine learning algorithms

Identification and Characterisation of the Murine Homologue of the Gene Responsible for Cystinosis, Ctns

BACKGROUND: Cystinosis is an autosomal recessive disorder characterised by an intralysosomal accumulation of cystine, and affected individuals progress to end-stage renal failure before the age of ten. The causative gene, CTNS, was cloned in 1998 and the encoded protein, cystinosin, was predicted to be a lysosomal membrane protein. RESULTS: We have cloned the murine homologue of CTNS, Ctns, and the encoded amino acid sequence is 92.6% similar to cystinosin. We localised Ctns to mouse chromosome 11 in a region syntenic to human chromosome 17 containing CTNS. Ctns is widely expressed in all tissues tested with the exception of skeletal muscle, in contrast to CTNS. CONCLUSIONS: We have isolated, characterised and localised Ctns, the murine homologue of CTNS underlying cystinosis. Furthermore, our work has brought to light the existence of a differential pattern of expression between the human and murine homologues, providing critical information for the generation of a mouse model for cystinosis

Building sustainability assessment

Although the social, economic and cultural indicators are of substantial importance, the concept of sustainable building is usually related to environmental characteristics. Any building level assessment method is complex and involves contradictory aspects. Moreover emphasizing qualitative criteria only increases confusion. The R&D and standardization is thus concentrated to transparency and usability of the environmental methods. Other directions of research are aiming at performance-based design and methods to take regional and cultural aspects into account. In this paper, the perspectives of the sustainability assessment of a whole building are presented based on the state-of-the art, feasibility study on performance analysis and development of extended LCA for buildings. Based on the case studies of building sustainability assessment using various tools, the environmental indicators were shown to be often of lesser importance than the other, soft ones. At the end, will be presented and discussed the first steps in the development of a building sustainability assessment method for Portuguese residential buildings.(undefined

LAU-0901, a novel platelet-activating factor receptor antagonist, confers enduring neuroprotection in experimental focal cerebral ischemia in the rat

LAU-0901, a novel platelet-activating factor (PAF) receptor antagonist, is highly neuroprotective in a rodent model of cerebral ischemia. This study was conducted to establish whether the neuroprotection induced by LAU-0901 persists with chronic survival. Male Sprague–Dawley rats were anesthetized with isoflurane and subjected to 2 h of temporary middle cerebral artery occlusion (MCAo) induced by means of a poly-l-lisine-coated intraluminal nylon suture. Animals were treated with either LAU-0901 (60 mg/kg) or vehicle (45% cyclodextran) administered i.p. at 2 h from onset of MCAo. They received neurobehavioral examinations during MCAo (60 min) and then at 1, 2, 3, 7, 14, 21 and 28 days followed by histopathology at 30 days. LAU-0901 significantly improved the behavior compared to the vehicle group, beginning on day 1 (by 29%, p = 0.00007) and persisting throughout a 30-day survival period (42%, p = 0.0001). Compared with vehicle treatment, LAU-0901 treatment significantly increased volume of non-infarcted brain tissue loss relative to the unlesioned hemisphere (16.3 ± 4.6% vs. 46.0 ± 10.3%, respectively). These results establish that LAU-0901 confers enduring ischemic neuroprotection.NIH Grant NS023002 (NGB

Quantitative in vivo and ex vivo confocal microscopy analysis of corneal cystine crystals in the Ctns−/− knockout mouse

PurposeThe purpose of this study was to assess the ability of quantitative in vivo confocal microscopy to characterize the natural history and detect changes in crystal volume in corneas from a novel animal model of cystinosis, the cystinosin (Ctns-/-) mouse.MethodsTwo Ctns−/− mice and one C57Bl/6 mouse were examined at each of the following time points: 2, 3, 5, 7, 10, 12, and 14 months of age. In vivo confocal microscopy scans were performed in 4 different regions of the cornea per eye. After, animals were sacrificed and cornea blocks evaluated for cell morphology using phalloidin and lymphocytic infiltration using CD45 antibodies by ex vivo confocal microscopy. Cystine crystal content in the cornea was measured by calculating the pixel intensity of the crystals divided by the stromal volume using Metamorph Image Processing Software.ResultsCorneal crystals were identified in Ctns−/− eyes beginning at 3 months of age and increased in density until 7–12 months, at which time animals begin to succumb to the disease and corneas become scarred and neovascularized. Older Ctns−/− mice (7 months and older) showed the presence of cell infiltrates that stained positively for CD45 associated with progressive keratocyte disruption. Finally, at 12 months of age, decreased cell density and endothelial distortion were detected.ConclusionsConfocal microscopy identified corneal crystals starting at 3 month old Ctns−/− eyes. Cystine crystals induce inflammatory and immune response with aging associated with loss of keratocyte and endothelial cells. These findings suggest that the Ctns−/− mouse can be used as a model for developing and evaluating potential alternative therapies for corneal cystinosis