Measuring road congestion

The methodology presented here allows to measure and monitor road congestion across Europe using data from TomTom in-vehicle navigation systems. The approach is based on the analysis of a large number of real vehicle speeds that have been measured on each road link and the application of algorithms that allow the estimation of congestion indicators for specific types of roads during selected time periods. The results include the detailed mapping of recurrent congestion both geographically and temporally, as well as the comparison of the quality of service of road networks between different zones. The data used represent real speed measurements from in-vehicle navigation systems for different time periods and days of the week. The large number of "probes" (over 1 trillion of measurements) gives a highly accurate and representative picture of the actual driving conditions across the European road network. The data collected are clustered in groups of speed profiles which represent change in average speed behaviour along a road link in five-minute time intervals over a 24-hour period. Each road link has a specific speed profile assigned per day of the week. The average speed on a specific link during a certain time period can be compared to the benchmark speed estimated for the link under free flow conditions or against selected threshold values. As a result, indicators of congestion for different time periods can be measured and compared across links, regions and countries.JRC.J.1-Economics of Climate Change, Energy and Transpor

Multifractality of the kicked rotor at the critical point of the Anderson transition

International audienceWe show that quantum wavepackets exhibit a sharp macroscopic peak as they spread in the vicinity of the critical point of the Anderson transition. The peak gives a direct access to the mutifractal properties of the wavefunctions and specifically to the multifractal dimension $d_2$. Our analysis is based on an experimentally realizable setup, the quantum kicked rotor with quasi-periodic temporal driving, an effectively 3-dimensional disordered system recently exploited to explore the physics of the Anderson transition with cold atoms

DNA methylation map of mouse and human brain identifies target genes in Alzheimer’s disease

The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer’s disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5’-end gene methylation patterns and observed their unique epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were used to identify aberrant DNA methylation changes that occurred in two mouse models of Alzheimer’s disease. We were able to translate these findings to patients with Alzheimer’s disease, identifying DNA methylation-associated silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease

Bilateral spontaneous hemotympanum: Case report

BACKGROUND: The most common causes of hemotympanum are therapeutic nasal packing, epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is characterized as idiopathic, when it is detected in the presence of chronic otitis media. A rare case of spontaneous bilateral hemotympanum in a patient treated with anticoagulants is presented herein. CASE PRESENTATION: A 72-year-old male presented with acute deterioration of hearing. In the patient's medical history aortic valve replacement 1 year before presentation was reported. Since then he had been administered regularly coumarinic anticoagulants, with INR levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed hearing loss bilaterally, with the conductive component predominating. Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized tomography scan showed the presence of fluid in the mastoid and middle ear bilaterally. Treatment was conservative and consisted of a 10-day course of antibiotics, anticongestants and temporary interruption of the anticoagulant therapy. After 3 weeks, normal tympanic membranes were found and hearing had returned to previous levels. CONCLUSION: Anticoagulant intake should be included in the differential diagnosis of hemotympanum, because its detection and appropriate treatment may lead to resolution of the disorder

Biogenic amines and their metabolites are differentially affected in the Mecp2-deficient mouse brain

International audienceBACKGROUND: Rett syndrome (RTT, MIM #312750) is a severe neurological disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Female patients are affected with an incidence of 1/15000 live births and develop normally from birth to 6-18 months of age before the onset of deficits in autonomic, cognitive, motor functions (stereotypic hand movements, impaired locomotion) and autistic features. Studies on Mecp2 mouse models, and specifically null mice, revealed morphological and functional alterations of neurons. Several functions that are regulated by bioaminergic nuclei or peripheral ganglia are impaired in the absence of Mecp2. RESULTS: Using high performance liquid chromatography, combined with electrochemical detection (HPLC/EC) we found that Mecp2(-/y) mice exhibit an alteration of DA metabolism in the ponto-bulbar region at 5 weeks followed by a more global alteration of monoamines when the disease progresses (8 weeks). Hypothalamic measurements suggest biphasic disturbances of norepinephrine and serotonin at pathology onset (5 weeks) that were found stabilized later on (8 weeks). Interestingly, the postnatal nigrostriatal dopaminergic deficit identified previously does not parallel the reduction of the other neurotransmitters investigated. Finally, dosage in cortical samples do not suggest modification in the monoaminergic content respectively at 5 and 8 weeks of age. CONCLUSIONS: We have identified that the level of catecholamines and serotonin is differentially affected in Mecp2(-/y) brain areas in a time-dependent fashion

Etude des déficits catécholaminergiques centraux chez la souris Mecp2-déficiente, modèle murin du syndrome de Rett

La méthylation de l’ADN est une modification majeure du génome des eucaryotes permettant de moduler l’expression génique et contrôler le développement des mammifères. La protéine Mecp2 (Methyl CpG binding protein 2), dont le gène est situé sur le chromosome X, appartient à la famille des protéines de liaison à l’ADN méthylé. Sur la base de sa structure et de ses interactions Mecp2 a été décrit comme un répresseur de l’expression des gènes. A l’heure actuelle, son implication en tant qu’activateur de la transcription et organisateur de la structure chromatinienne lui confère un rôle plus global dans la régulation de l’épigénome. Des mutations de MECP2 conduisent à des troubles neurologiques dont le principal est le syndrome de Rett (RTT). Cette pathologie dominante liée à l’X affecte principalement les jeunes filles (incidence: 1/15000 naissances). Même si les causes précises du phénotype RTT ne sont pas connues, le profil d’expression de Mecp2 est en lien avec la synaptogenèse, la maturation et la maintenance des réseaux neuronaux. A mon arrivée en thèse l’équipe qui m’a accueilli venait d’identifier des déficits neuronaux, affectant notamment les groupes catécholaminergiques bulbaires et périphériques, à l’origine de troubles respiratoires chez un modèle murin de cette pathologie. Mon travail de thèse a permis de caractériser l’évolution postnatale des déficits moteurs et physiologiques affectant la souris Mecp2-déficiente. L’étude de structures catécholaminergiques d’intérêt telles que la Substantia Nigra et le Locus Coeruleus a révélé que les neurones dopaminergiques et noradrénergiques centraux ont un métabolisme affecté. Le nombre de neurones immunomarqués apparait significativement réduit dans ces groupes ce qui résulterait d’une perte progressive du phénotype « catécholaminergique », en l’absence de mort cellulaire. Nos données suggèrent que ces atteintes constituent un corrélat neuropathologique aux troubles comportementaux observés chez les souris Mecp2-déficientes. Ainsi certains troubles moteurs ont pu être améliorés, à l’aide d’un agent pharmacologique pro-dopaminergique, la L-Dopa. En relation avec les déficits en Bdnf (Brain-derived neurotrophic factor) décrits chez les patientes et les souris Mecp2-déficientes, nous avons identifié qu’une modification du dosage de Mecp2 induit une dérégulation de gènes (Htt, Hap1) codant des protéines impliquées dans le transport intracellulaire des vésicules de Bdnf. Nos travaux nous permettent de postuler que chez la souris Mecp2-déficiente, une altération de la dynamique de transport des vésicules chargées en Bdnf pourrait exacerber le déficit d’expression de cette neurotrophine. Notre traitement des souris Mecp2-déficientes par la cystéamine, une molécule capable d’agir sur les contenus, la libération et la sécrétion du Bdnf permet d’augmenter la survie des animaux et de réduire leurs troubles moteurs. Nos résultats montrent que les déficiences en Mecp2 entrainent des déficits de transport axonal du Bdnf qui s’ajoutent aux déficits de production du Bdnf. Par ailleurs, avec l’utilisation d’agents pharmacologiques agissant sur ce transport, nous offrons de nouvelles perspectives thérapeutiques.DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. The protein Mecp2 (Methyl CpG binding protein 2), encoded by a gene located on the X chromosome, belongs to the ‘Methyl Binding domain’ protein family. Based on its structure and its interactions Mecp2 has historically been described as a repressor of expression for many genes. Currently, its involvement as an activator of transcription and its role in chromatin architecture suggests that it could be a global regulator of the epigenome. Mutations in MECP2 lead to neurological disorders, among which Rett syndrome (RTT). This dominant X-linked pathology mainly affects girls (incidence: 1/15000 live births). Although the precise causes of the RTT phenotype are unknown, the pattern of Mecp2 expression is related to synaptogenesis, maturation and neuromaintenance. Before my integration in the ‘Human Neurogenetics’ team, this group identified neural deficits, affecting brainstem and peripheral catecholaminergic cell groups, causing respiratory disturbances in a mouse model of this disease. My thesis work enabled the characterization of the postnatal physiological and motor deficits affecting the Mecp2-deficient mice. The study of catecholaminergic structures of interest such as the substantia nigra pars compacta and the locus coeruleus has revealed that the central noradrenergic and dopaminergic neurons are affected in their metabolism. The number of immunolabelled neurons of these groups appears significantly reduced and would result in a gradual loss of the mature ‘catecholaminergic’ phenotype, in the absence of cell death. Our data suggest that these defects are a neuropathological correlate for behavioral disorders observed in Mecp2-deficient mice. Some motor deficits have been improved, with L-Dopa, a pro-dopaminergic drug. In relation with Bdnf (Brain-derived neurotrophic factor) reduction described in patients and Mecp2-deficient mice, we identified that a change in the dosage of Mecp2 deregulates genes (Htt, Hap1) encoding proteins involved in the intracellular transport of Bdnf. Our work allows to postulate that in the Mecp2-deficient neurons, an altered dynamics of Bdnf vesicles transport could exacerbate the deficit of expression of this neurotrophin. Our treatment of Mecp2-deficient mice with cysteamine, a molecule able to increase Bdnf contents and enhancing its release and secretion, increased the survival of the animals and reduced their motor defects. Our results show that the Mecp2-deficiencies lead to alteration in the axonal transport of Bdnf in addition to deficits in Bdnf production. In addition, by the use of pharmacological agents that affect this transport, we offer new therapeutic perspectives

Asymptotic Degradation of Linear Regression Estimates with Strategic Data Sources

International audienceWe consider the problem of linear regression from strategic data sources with a public good component, i.e., when data is provided by strategic agents who seek to minimize an individual provision cost for increasing their data's precision while benefiting from the model's overall precision. In contrast to previous works, our model tackles the case where there is uncertainty on the attributes characterizing the agents' data -- a critical aspect of the problem when the number of agents is large. We provide a characterization of the game's equilibrium, which reveals an interesting connection with optimal design. Subsequently, we focus on the asymptotic behavior of the covariance of the linear regression parameters estimated via generalized least squares as the number of data sources becomes large. We provide upper and lower bounds for this covariance matrix and we show that, when the agents' provision costs are superlinear, the model's covariance converges to zero but at a slower rate relative to virtually all learning problems with exogenous data. On the other hand, if the agents' provision costs are linear, this covariance fails to converge. This shows that even the basic property of consistency of generalized least squares estimators is compromised when the data sources are strategic

Asymptotic Degradation of Linear Regression Estimates with Strategic Data Sources

International audienceWe consider the problem of linear regression from strategic data sources with a public good component, i.e., when data is provided by strategic agents who seek to minimize an individual provision cost for increasing their data's precision while benefiting from the model's overall precision. In contrast to previous works, our model tackles the case where there is uncertainty on the attributes characterizing the agents' data -- a critical aspect of the problem when the number of agents is large. We provide a characterization of the game's equilibrium, which reveals an interesting connection with optimal design. Subsequently, we focus on the asymptotic behavior of the covariance of the linear regression parameters estimated via generalized least squares as the number of data sources becomes large. We provide upper and lower bounds for this covariance matrix and we show that, when the agents' provision costs are superlinear, the model's covariance converges to zero but at a slower rate relative to virtually all learning problems with exogenous data. On the other hand, if the agents' provision costs are linear, this covariance fails to converge. This shows that even the basic property of consistency of generalized least squares estimators is compromised when the data sources are strategic

Asymptotic Degradation of Linear Regression Estimates with Strategic Data Sources

International audienceWe consider the problem of linear regression from strategic data sources with a public good component, i.e., when data is provided by strategic agents who seek to minimize an individual provision cost for increasing their data's precision while benefiting from the model's overall precision. In contrast to previous works, our model tackles the case where there is uncertainty on the attributes characterizing the agents' data -- a critical aspect of the problem when the number of agents is large. We provide a characterization of the game's equilibrium, which reveals an interesting connection with optimal design. Subsequently, we focus on the asymptotic behavior of the covariance of the linear regression parameters estimated via generalized least squares as the number of data sources becomes large. We provide upper and lower bounds for this covariance matrix and we show that, when the agents' provision costs are superlinear, the model's covariance converges to zero but at a slower rate relative to virtually all learning problems with exogenous data. On the other hand, if the agents' provision costs are linear, this covariance fails to converge. This shows that even the basic property of consistency of generalized least squares estimators is compromised when the data sources are strategic