DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.

The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature.

Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans.

Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.

Uncertainty associated with Monte Carlo radiation transport in radionuclide metrology

In radionuclide metrology, Monte Carlo (MC) simulation is widely used to compute parameters associated with primary measurements or calibration factors. Although MC methods are used to estimate uncertainties, the uncertainty associated with radiation transport in MC calculations is usually difficult to estimate. Counting statistics is the most obvious component of MC uncertainty and has to be checked carefully, particularly when variance reduction is used. However, in most cases fluctuations associated with counting statistics can be reduced using sufficient computing power. Cross-section data have intrinsic uncertainties that induce correlations when apparently independent codes are compared. Their effect on the uncertainty of the estimated parameter is difficult to determine and varies widely from case to case. Finally, the most significant uncertainty component for radionuclide applications is usually that associated with the detector geometry. Recent 2D and 3D x-ray imaging tools may be utilized, but comparison with experimental data as well as adjustments of parameters are usually inevitable.

The role of the renal mineralocorticoid versus the glucocorticoid receptor in renal sodium and potassium transport

Dans le néphron distal sensible à l'aldostérone, le récepteur aux minéralocorticoïdes (RM) et le récepteur aux glucocorticoids (RG) sont exprimés et peuvent être liés et activés par l'aldostérone et le Cortisol, respectivement. La réabsorption rénale de sodium est principalement contrôlée par le RM. Cependant, des modèles expérimentaux in vitro et in vivo suggèrent que le RG pourrait également jouer un rôle dans le transport rénal du sodium. Afin d'étudier l'implication du RG et/ou du RM exprimés dans les cellules épithéliales adultes dans le transport rénal du sodium, nous avons généré deux modèles de souris, dans lesquelles l'expression du RG (Nr3c1Pax8/LC1) ou du RM (Nr3c2Pax8/LC1) peut être abolie de manière inductible et cela spécifiquement dans les tubules rénaux. Les souris déficientes pour le gène du RM survivent mais développent un phénotype sévère de PHA-1, caractérisé par un retard de croissance, une augmentation des niveaux urinaires de Na+, une diminution de la concentration du Na+ dans le plasma, une hyperkaliémie et une augmentation des niveaux d'aldostérone plasmatique. Ce phénotype empire et devient létal lorsque les souris sont nourries avec une diète déficiente en sodium. Les niveaux d'expression en protéine de NCC, de la forme phosphorylée de NCC et de aENaC sont diminués, alors que l'expression en ARN messager et en protéine du RG est augmentée. Une diète riche en Na+ et pauvre en K+ ne corrige pas la concentration élevée d'aldostérone dans le plasma pour la ramener à des niveaux conformes, mais est suffisante pour corriger la perte de poids et les niveaux anormaux des électrolytes dans le plasma et l'urine. -- In the aldosterone-sensitive distal nephron, both the mineralocorticoid (MR) and the glucocorticoid (GR) receptor are expressed. They can be bound and activated by aldosterone and Cortisol, respectively. Renal Na+ reabsorption is mainly controlled by MR. However, in vitro and in vivo experimental models suggest that GR may play a role in renal Na+ transport. Therefore, to investigate the implication of MR and/or GR in adult epithelial cells in renal sodium transport, we generated inducible renal tubule- specific MR (Nr3c2Pax8/LC1) and GR (Nr3c1Pax8/LC1) knockout mice. MR-deficient mice survived but developed a severe PHA-1 phenotype with failure to thrive, higher urinary Na+, decreased plasma Na+ levels, hyperkalemia and higher levels of plasma aldosterone. This phenotype further worsened and became lethal under a sodium-deficient diet. NCC protein expression and its phosphorylated form, as well as aENaC protein level were downregulated, whereas the mRNA and protein expression of GR was increased. A diet rich in Na+and low in K+ did not normalize plasma aldosterone to control levels, but was sufficient to restore body weight, plasma and urinary electrolytes. Upon switch to a Na+-deficient diet, GR-mutant mice exhibited transient increased urinary Na+ and decreased K+ levels, with transitory higher plasma K+ concentration preceded by a significant increase in plasma aldosterone levels within the 12 hours following diet switch. We found no difference in urinary aldosterone levels, plasma Na+ concentration and plasma corticosterone levels. Moreover, NHE3, NKCC2, NCC

Tackling Societal Challenges Related to Ageing and Transport Transition: An Introduction to Philosophical Principles of Causation Adapted to the Biopsychosocial Model

In geriatrics, driving cessation is addressed within the biopsychosocial model. This has broadened the scope of practitioners, not only in terms of assessing fitness to drive, but also by helping to maintain social engagements and provide support for transport transition. Causes can be addressed at different levels by adapting medication, improving physical health, modifying behaviour, adapting lifestyle, or bringing changes to the environment. This transdisciplinary approach requires an understanding of how different disciplines are linked to each other. This article reviews the philosophical principles of causality between fields and provides a framework for understanding causality within the biopsychosocial model. Understanding interlevel constraints should help practitioners overcome their differences, and favor transversal approaches to driving cessation.

Cyclosporine A kinetics in brain cell cultures and its potential of crossing the blood-brain barrier.

There is an increasing need to develop improved systems for predicting the safety of xenobiotics. However, to move beyond hazard identification the available concentration of the test compounds needs to be incorporated. In this study cyclosporine A (CsA) was used as a model compound to assess the kinetic profiles in two rodent brain cell cultures after single and repeated exposures. CsA induced-cyclophilin B (Cyp-B) secretion was also determined as CsA-specific pharmacodynamic endpoint. Since CsA is a potent p-glycoprotein substrate, the ability of this compound to cross the blood-brain barrier (BBB) was also investigated using an in vitro bovine model with repeated exposures up to 14days. Finally, CsA uptake mechanisms were studied using a parallel artificial membrane assay (PAMPA) in combination with a Caco-2 model. Kinetic results indicate a low intracellular CsA uptake, with no marked bioaccumulation or biotransformation. In addition, only low CsA amounts crossed the BBB. PAMPA and Caco-2 experiments revealed that CsA is mostly trapped to lipophilic compartments and exits the cell apically via active transport. Thus, although CsA is unlikely to enter the brain at cytotoxic concentrations, it may cause alterations in electrical activity and is likely to increase the CNS concentration of other compounds by occupying the BBBs extrusion capacity. Such an integrated testing system, incorporating BBB, brain culture models and kinetics could be applied for assessing neurotoxicity potential of compounds.

Influence of transport and time on blood variables commonly measured for the athlete biological passport.

Some recent studies have characterized the stability of blood variables commonly measured for the Athlete Biological Passport. The aim of this study was to characterize the impact of different shipments conditions and the quality of the results returned by the haematological analyzer. Twenty-two healthy male subjects provided five EDTA tubes each. Four shipment conditions (24, 36, 48, 72 h) under refrigerated conditions were tested and compared to a set of samples left in the laboratory also under refrigerated conditions (group control). All measurements were conducted using two Sysmex XT-2000i analyzers. Haemoglobin concentration, reticulocytes percentage, and OFF-score numerical data were the same for samples analyzed just after collection and after a shipment under refrigerated conditions up to 72 h. Detailed information reported especially by the differential (DIFF) channel scatterplot of the Sysmex XT-2000i indicated that there were signs of blood deterioration, but were not of relevance for the variables used in the Athlete Biological Passport. As long as the cold chain is guaranteed, the time delay between the collection and the analyses of blood variables can be extended. Copyright© 2015 John Wiley & Sons, Ltd.

PEC1/AtABCG32 transport function in cuticle biosynthesis

Most aerial parts of the plants are covered by a hydrophobic coating called cuticle. The cuticle is formed of cutin, a complex mixture of esterified fatty acids that are embedded and associated with waxes. The cuticle often appears as a superposition of layers of different composition: The cuticle proper formed of cutin and a mixture of waxes and underneath, the cuticle layer containing cutin, intracuticular waxes and polysaccharides of the cell wall. In addition to its involvement in plant development by preventing organ fusions, the cuticle acts as a barrier to prevent water loss and protect plants against environmental aggressions such as excessive radiation or pathogens attacks. PEC1/AtABCG32 is an ABC transporter from the PDR family involved in cutin biosynthesis. Characterization of the peci mutant in Arabidopsis thaliana showed that PEC1 plays a significant role in the diffusion barrier formation in leaves and petals. The cuticles of leaves and flowers of peci are permeable and the cuticular layer rather than the cuticular proper was altered in the petals, underlining the importance of this particular layer in the maintenance of the diffusion barrier. Chemical analysis on the flower cutin monomer composition of ped mutant revealed a decrease in hydroxylated cutin monomers, suggesting a function of PEC1 in the incorporation of these monomers in the polymer cutin. However, the exact nature of the substrates of PEC1 remained elusive. PEC1 homologues in barley and rice, respectively HvABCG31/EIBI1 and OsABCG31, are also implicated in cuticle biosynthesis. Interestingly, the rice mutant displays more severe phenotypes such as dwarfism and spreading necrosis conducting to the seedling death. In this work, we further characterized osabcg31 mutant and hairpin-RNAi downregulated OsABCG31 plant lines showing reduced growth and cuticle permeability. Our analysis showed a decrease in hydroxylated cutin monomers and severe disruptions in the cuticle, which explain the permeability. Further insights into the function of the cuticle in rice resistance/susceptibility to Pathogens were obtained after inoculation with Magnaporthe oryzae, the fungus responsible for the rice blast disease. Osabcg31 as well as the transgenic lines downregulating OsABCG31 showed increased resistance to the fungus. However, only later steps of infection are reduced . and no impact is obseived on the germination or penetration stages, suggesting that the cuticle disruption per se is not responsible for the resistance. We further investigated the cause of the resistance by analyzing the expression of defense related gene in osabcg31 prior to infection. We found that osabcg31 constitutively express defense related genes, which may explain the resistance, the dwarfism and the cell death. osabcg31 is thus a tool to study the connection between cuticle, plant development and defense signaling networks in rice. The transport function of PEC1 family members is still unknown. In order to link cutin biosynthesis and transport activity, we combined ped mutation with mutations in cutin synthesis related genes. Here, we show that PEC1 acts independently from GPAT4 and GPAT8 pathway and partially overlaps with GPAT6 biosynthesis pathway that leads to the production of hydroxylated C16 cutin precursor 2-Mono(10,16-dihydroxyhexadecanoylJglycerol (2-MHG). In addition, we noticed that despite a comparable cutin monomer composition, ped mutant leaves cuticle are permeable while that of gpat6 mutant are not. This finding raises the possibility of PEC1 being required for the incorporation of C16 hydroxylated monomers and their structural arrangement rather than their direct transport towards the cuticle. A careful investigation of the cuticle permeability, cutin composition and ultrastructure during leave development in Wt plants and ped mutants revealed a possible different regulation of several pathways of cutin biosynthesis and showed the importance of PEC1 function early during leave cuticle maturation. In order to elucidate the transport activity of PEC1, we successfully expressed PEC1 in Nicotiana benthamiana plant system for direct transport experiments. This system will be used to test the PEC 1-dependent transport of potential substrates such as sn-2-monoacylglycerol loaded with a hydroxylated C16 fatty acid. -- Toutes les parties aériennes des plantes sont recouvertes d'une couche hydrophobe appelée «cuticule». Cette cuticule est composée de cutine, un polymère d'acides gras estérifiés, et de cires. La cuticule apparaît souvent sous forme de couches superposées: une première couche extérieure appelée «cuticle proper» formée de cutine et d'un mélange de cires, et une deuxième couche, la «cuticle layer», formée de cutine associée à des cires intracuticulaires et des polysaccharides pariétaux. La cuticule joue le rôle de barrière prévenant contre la perte d'eau et les agressions environnementales. AtABCG32/PEC1 est un transporteur ABC de la famille des PDR impliqué dans la synthèse de la cutine. L'étude du mutant peci d'Arabidopsis thaliana a révélé une fonction de PEC1 dans la formation de la barrière de diffusion. La cuticule des feuilles et fleurs de peci est perméable. Des altérations de la «cuticle layer» ont été démontrées, soulignant son importance dans le maintien de la barrière. L'analyse de la composition de la cutine de peci a montré une réduction spécifique en monomères hydroxylés, suggérant un rôle de PEC1 dans leur incorporation dans la cuticule. Cependant, la nature exacte des substrats de PEC1 n'a pas été identifiée. PEC1 possède deux homologues chez l'orge et le riz, respectivement HvABCG31 et OsABCG31, et qui sont impliqués dans la biosynthèse de la cuticule. Chez le riz, des phénotypes plus sévères ont été observés tels que nanisme et nécroses conduisant à la mort des jeunes plants. Dans cette étude, nous avons continué la caractérisation de osabcg31 ainsi que des lignées de riz sous exprimant le gène OsABCG31 et présentant une cuticule perméable tout en ayant une meilleure croissance. Notre étude a démontré une réduction des monomères hydroxylés de cutine et une désorganisation de la structure de la cuticule, aggravée dans le mutant osabcg31. Ce résultat explique la perméabilité observée. Des mformations P|us approfondies sur l'implication de la cuticule dans la résistance aux pathogènes ont été obtenues après inoculation du mutant osabcg31 et les lignées sous- exprimant OsABCG31 avec une souche virulente de Magnaporthe Oryzae, le champignon responsable de la pyriculariose du riz. Les différentes lignées testées ont démontré une résistance au pathogène. Cependant, seules les étapes tardives de l'infection sont réduites et aucun impact n'est observé sur la germination des spores ou la pénétration du champignon, suggérant que les modifications de la cuticule ne sont pas directement à l'origine de la résistance. L'analyse de l'expression de gènes impliqués dans la résistance à Magnaporthe.oryzae a mis en évidence l'expression constitutive de ces gènes en l'absence de tout contact avec le pathogène. Ceci explique la résistance, le nanisme et la mort cellulaire observés. Ainsi, osabcg31 représente un outil efficace pour l'étude intégrée des systèmes de régulation de la défense, de développement des plantes et la cuticule. La nature des substrats transportés par PEC1/AtABCG32 reste inconnue. Dans le but d'établir une liaison entre biosynthèse de cutine et transport des précurseurs par PEC1, la mutation peci a été combinée avec des mutants impliqués dans différentes voies de biosynthèse. Cette étude a démontré une fonction indépendante de PEC1 de la voie de biosynthèse impliquant les enzymes GPAT4 et GPAT8, et une fonction partiellement indépendante de la voie impliquant GPAT6 qui mène à la production de précurseurs sn-2- monoacylglycerol chargés en acides gras en C16 (2-MHG). De plus, malgré un profil similaire en monomères de cutine, gpat6 conserve une cuticule imperméable alors que celle de PEC1 est perméable. Ceci suggère que PEC1 est nécessaire à l'incorporation des monomères en C16 et leur arrangement structurel plutôt que simplement à leur transport direct. L'étude approfondie de la perméabilité cuticulaire, de la structure ainsi que de la composition en cutine pendant le développement des feuilles de peci et la plante sauvage a révélé l'existence de différentes régulations des voies de biosynthèses des monomères et a démontré l'importance de PEC1 dans les premières étapes de la mise en place de la cuticule. Pour identifier les substrats transportés, l'expression de PEC1 chez le système hétérologue Nicotiana benthamiana a été conduite avec succès. Ce système sera utilisé pour tester le transport de substrats potentiels tels que le sn-2-monoacylglycerol chargé en acide gras en C16.

Aetiologies of pulseless electrical activity in out-of-hospital cardiac arrests:A retrospective study and analysis of specific causes

Background: Pulseless electrical activity (PEA) cardiac arrest is defined as a cardiac arrest (CA) presenting with a residual organized electrical activity on the electrocardiogram. In the last decades, the incidence of PEA has regularly increased, compared to other types of CA like ventricular fibrillation or pulseless ventricular tachycardia. PEA is frequently induced by reversible conditions. The "4 (or 5) H" & "4 (or 5) T" are proposed as a mnemonic to asses for Hypoxia, Hypovolemia, Hypo- /Hyperkalaemia, Hypothermia, Thrombosis (cardiac or pulmonary), cardiac Tamponade, Toxins, and Tension pneumothorax. Other pathologies (intracranial haemorrhage, severe sepsis, myocardial contraction dysfunction) have been identified as potential causes for PEA, but their respective probability and frequencies are unclear and they are not yet included into the resuscitation guidelines. The aim of this study was to analyse the aetiologies of PEA out-of-hospital CA, in order to evaluate the relative frequencies of each cause and therefore to improve the management of patients suffering a PEA cardiac arrest. Method: This retrospective study was based on data routinely and prospectively collected for each PEMS intervention. All adult patients treated from January 1st 2002 to December 2012 31st by the PEMS for out-of-hospital cardiac arrest, with PEA as the first recorded rhythm, and admitted to the emergency department (ED) of the Lausanne University Hospital were included. The aetiologies of PEA cardiac arrest were classified into subgroups, based on the classical H&T's classification, supplemented by four other subgroups analysis: trauma, intra-cranial haemorrhage (ICH), non-ischemic cardiomyopathy (NIC) and undetermined cause. Results: 1866 OHCA were treated by the PEMS. PEA was the first recorded rhythm in 240 adult patients (13.8 %). After exclusion of 96 patients, 144 patients with a PEA cardiac arrest admitted to the ED were included in the analysis. The mean age was 63.8 ± 20.0 years, 58.3% were men and the survival rate at 48 hours was 29%. 32 different causes of OHCA PEA were established for 119 patients. For 25 patients (17.4 %), we were unable to attribute a specific cause for the PEA cardiac arrest. Hypoxia (23.6 %), acute coronary syndrome (12.5%) and trauma (12.5 %) were the three most frequent causes. Pulmonary embolism, Hypovolemia, Intoxication and Hyperkaliemia occurs in less than 10% of the cases (7.6 %, 5.6 %, 3.5%, respectively 2.1 %). Non ischemic cardiomyopathy and intra-cranial haemorrhage occur in 8.3 % and 6.9 %, respectively. Conclusions: According to our results, intra-cranial haemorrhage and non-ischemic cardiomyopathy represent noticeable causes of PEA in OHCA, with a prevalence equalling or exceeding the frequency of classical 4 H's and 4 T's aetiologies. These two pathologies are potentially accessible to simple diagnostic procedures (native CT-scan or echocardiography) and should be included into the 4 H's and 4 T's mnemonic.

Analyse de réseau piéton et gestion scolaire: sinuosité, centricité et transport optimal régularisé

Que ce soit d'un point de vue, urbanistique, social, ou encore de la gouvernance, l'évolution des villes est un défi majeur de nos sociétés contemporaines. En offrant la possibilité d'analyser des configurations spatiales et sociales existantes ou en tentant de simuler celles à venir, les systèmes d'information géographique sont devenus incontournables dans la gestion et dans la planification urbaine. En cinq ans la population de la ville de Lausanne est passée de 134'700 à 140'570 habitants, alors que les effectifs de l'école publique ont crû de 12'200 à 13'500 élèves. Cet accroissement démographique associé à un vaste processus d'harmonisation de la scolarité obligatoire en Suisse ont amené le Service des écoles à mettre en place et à développer en collaboration avec l'université de Lausanne des solutions SIG à même de répondre à différentes problématiques spatiales. Établies en 1989, les limites des établissements scolaires (bassins de recrutement) ont dû être redéfinies afin de les réadapter aux réalités d'un paysage urbain et politique en pleine mutation. Dans un contexte de mobilité et de durabilité, un système d'attribution de subventions pour les transports publics basé sur la distance domicile-école et sur l'âge des écoliers, a été conçu. La réalisation de ces projets a nécessité la construction de bases de données géographiques ainsi que l'élaboration de nouvelles méthodes d'analyses exposées dans ce travail. Cette thèse s'est ainsi faite selon une dialectique permanente entre recherches théoriques et nécessités pratiques. La première partie de ce travail porte sur l'analyse du réseau piéton de la ville. La morphologie du réseau est investiguée au travers d'approches multi-échelles du concept de centralité. La première conception, nommée sinuo-centralité ("straightness centrality"), stipule qu'être central c'est être relié aux autres en ligne droite. La deuxième, sans doute plus intuitive, est intitulée centricité ("closeness centrality") et exprime le fait qu'être central c'est être proche des autres (fig. 1, II). Les méthodes développées ont pour but d'évaluer la connectivité et la marchabilité du réseau, tout en suggérant de possibles améliorations (création de raccourcis piétons). Le troisième et dernier volet théorique expose et développe un algorithme de transport optimal régularisé. En minimisant la distance domicile-école et en respectant la taille des écoles, l'algorithme permet de réaliser des scénarios d'enclassement. L'implémentation des multiplicateurs de Lagrange offre une visualisation du "coût spatial" des infrastructures scolaires et des lieux de résidence des écoliers. La deuxième partie de cette thèse retrace les aspects principaux de trois projets réalisés dans le cadre de la gestion scolaire. À savoir : la conception d'un système d'attribution de subventions pour les transports publics, la redéfinition de la carte scolaire, ou encore la simulation des flux d'élèves se rendant à l'école à pied. *** May it be from an urbanistic, a social or from a governance point of view, the evolution of cities is a major challenge in our contemporary societies. By giving the opportunity to analyse spatial and social configurations or attempting to simulate future ones, geographic information systems cannot be overlooked in urban planning and management. In five years, the population of the city of Lausanne has grown from 134'700 to 140'570 inhabitants while the numbers in public schools have increased from 12'200 to 13'500 students. Associated to a considerable harmonisation process of compulsory schooling in Switzerland, this demographic rise has driven schooling services, in collaboration with the University of Lausanne, to set up and develop GIS capable of tackling various spatial issues. Established in 1989, the school districts had to be altered so that they might fit the reality of a continuously changing urban and political landscape. In a context of mobility and durability, an attribution system for public transport subventions based on the distance between residence and school and on the age of the students was designed. The implementation of these projects required the built of geographical databases as well as the elaboration of new analysis methods exposed in this thesis. The first part of this work focuses on the analysis of the city's pedestrian network. Its morphology is investigated through multi-scale approaches of the concept of centrality. The first conception, named the straightness centrality, stipulates that being central is being connected to the others in a straight line. The second, undoubtedly more intuitive, is called closeness centrality and expresses the fact that being central is being close to the others. The goal of the methods developed is to evaluate the connectivity and walkability of the network along with suggesting possible improvements (creation of pedestrian shortcuts).The third and final theoretical section exposes and develops an algorithm of regularised optimal transport. By minimising home to school distances and by respecting school capacity, the algorithm enables the production of student allocation scheme. The implementation of the Lagrange multipliers offers a visualisation of the spatial cost associated to the schooling infrastructures and to the student home locations. The second part of this thesis recounts the principal aspects of three projects fulfilled in the context of school management. It focuses namely on the built of an attribution system for public transport subventions, a school redistricting process and on simulating student pedestrian flows.