L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.

During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a system works in coordination is not well understood. Cross-regulatory interactions between different signalling pathways and redundancy between them can increase precision and fidelity of guidance systems. Immunoglobulin superfamily proteins of the NCAM and L1 families couple specific substrate recognition and cell adhesion with the activation of receptor tyrosine kinases. Thus it has been shown that L1CAM-mediated cell adhesion promotes the activation of the EGFR (erbB1) from Drosophila to humans. Here we explore the specificity of the molecular interaction between L1CAM and the erbB receptor family. We show that L1CAM binds physically erbB receptors in both heterologous systems and the mammalian developing brain. Different Ig-like domains located in the extracellular part of L1CAM can support this interaction. Interestingly, binding of L1CAM to erbB enhances its response to neuregulins. During development this may synergize with the activation of erbB receptors through L1CAM homophilic interactions, conferring diffusible neuregulins specificity for cells or axons that interact with the substrate through L1CAM

Graphon Estimation in bipartite graphs with observable edge labels and unobservable node labels

Many real-world data sets can be presented in the form of a matrix whose entries correspond to the interaction between two entities of different natures (number of times a web user visits a web page, a student's grade in a subject, a patient's rating of a doctor, etc.). We assume in this paper that the mentioned interaction is determined by unobservable latent variables describing each entity. Our objective is to estimate the conditional expectation of the data matrix given the unobservable variables. This is presented as a problem of estimation of a bivariate function referred to as graphon. We study the cases of piecewise constant and H\"older-continuous graphons. We establish finite sample risk bounds for the least squares estimator and the exponentially weighted aggregate. These bounds highlight the dependence of the estimation error on the size of the data set, the maximum intensity of the interactions, and the level of noise. As the analyzed least-squares estimator is intractable, we propose an adaptation of Lloyd's alternating minimization algorithm to compute an approximation of the least-squares estimator. Finally, we present numerical experiments in order to illustrate the empirical performance of the graphon estimator on synthetic data sets

Atmospheric CO2 modeling at the regional scale: an intercomparison of 5 meso-scale atmospheric models

Atmospheric CO2 modeling in interaction with the surface fluxes, at the regional scale is developed within the frame of the European project CarboEurope-IP and its Regional Experiment component. In this context, five meso-scale meteorological models participate in an intercomparison exercise. Using a common experimental protocol that imposes a large number of rules, two days of the CarboEurope Regional Experiment Strategy (CERES) campaign are simulated. A systematic evaluation of the models is done in confrontation with the observations, using statistical tools and direct comparisons. Thus, temperature and relative humidity at 2 m, wind direction, surface energy and CO2 fluxes, vertical profiles of potential temperature as well as in-situ CO2 concentrations comparisons between observations and simulations are examined. This intercomparison exercise shows also the models ability to represent the meteorology and carbon cycling at the synoptic and regional scale in the boundary layer, but also points out some of the major shortcomings of the models

The SURFEXv7.2 land and ocean surface platform for coupled or offline simulation of Earth surface variables and fluxes

CC Attribution 3.0 License.Final revised paper also available at http://www.geosci-model-dev.net/6/929/2013/gmd-6-929-2013.pdfInternational audienceSURFEX is a new externalized land and ocean surface platform that describes the surface fluxes and the evolution of four types of surface: nature, town, inland water and ocean. It can be run either coupled or in offline mode. It is mostly based on pre-existing, well validated scientific models. It can be used in offline mode (from point scale to global runs) or fully coupled with an atmospheric model. SURFEX is able to simulate fluxes of carbon dioxide, chemical species, continental aerosols, sea salt and snow particles. It also includes a data assimilation module. The main principles of the organization of the surface are described first. Then, a survey is made of the scientific module (including the coupling strategy). Finally the main applications of the code are summarized. The current applications are extremely diverse, ranging from surface monitoring and hydrology to numerical weather prediction and global climate simulations. The validation work undertaken shows that replacing the pre-existing surface models by SURFEX in these applications is usually associated with improved skill, as the numerous scientific developments contained in this community code are used to good advantage

CO₂ dispersion modelling over Paris region within the CO₂-MEGAPARIS project

Accurate simulation of the spatial and temporal variability of tracer mixing ratios over urban areas is a challenging and interesting task needed to be performed in order to utilise CO₂ measurements in an atmospheric inverse framework and to better estimate regional CO₂ fluxes. This study investigates the ability of a high-resolution model to simulate meteorological and CO₂ fields around Paris agglomeration during the March field campaign of the CO₂-MEGAPARIS project. The mesoscale atmospheric model Meso-NH, running at 2 km horizontal resolution, is coupled with the Town Energy Balance (TEB) urban canopy scheme and with the Interactions between Soil, Biosphere and Atmosphere CO₂-reactive (ISBA-A-gs) surface scheme, allowing a full interaction of CO₂ modelling between the surface and the atmosphere. Statistical scores show a good representation of the urban heat island (UHI) with stronger urban–rural contrasts on temperature at night than during the day by up to 7 °C. Boundary layer heights (BLH) have been evaluated on urban, suburban and rural sites during the campaign, and also on a suburban site over 1 yr. The diurnal cycles of the BLH are well captured, especially the onset time of the BLH increase and its growth rate in the morning, which are essential for tall tower CO₂ observatories. The main discrepancy is a small negative bias over urban and suburban sites during nighttime (respectively 45 m and 5 m), leading to a few overestimations of nocturnal CO₂ mixing ratios at suburban sites and a bias of +5 ppm. The diurnal CO₂ cycle is generally well captured for all the sites. At the Eiffel tower, the observed spikes of CO₂ maxima occur every morning exactly at the time at which the atmospheric boundary layer (ABL) growth reaches the measurement height. At suburban ground stations, CO₂ measurements exhibit maxima at the beginning and at the end of each night, when the ABL is fully contracted, with a strong spatio-temporal variability. A sensitivity test without urban parameterisation removes the UHI and underpredicts nighttime BLH over urban and suburban sites, leading to large overestimation of nocturnal CO₂ mixing ratio at the suburban sites (bias of +17 ppm). The agreement between observation and prediction for BLH and CO₂ concentrations and urban–rural increments, both day and night, demonstrates the potential of using the urban mesoscale system in the context of inverse modellin

Evaluation of the effectiveness of telemedical technologies in patients with digestive diseases

BACKGROUND: The use of telemedical technologies (TMT) is widespread in providing care to patients of various profiles. However, TMTs are hardly ever used in gastroenterology, despite the extensive digitalization of healthcare. Potential sites for the use of TMTs among gastroenterological patients were assessed. AIM: The study aimed to assess the effectiveness and benefits of TMTs in patients with digestive diseases. Patients with colorectal cancer (CRC): Screening and postoperative management. The TMT intervention increased the number of patients screened for CRC compared to standard face-to-face counseling. In addition, the quality of preparation for colonoscopy was higher in patients who interacted with the physician via TMTs compared to the control group. Most studies reported positive effects of TMTs on quality of life and physical activity in patients with CRC. However, the study by K. Beaver et al. showed that the incidence of CRC recurrence did not differ in the TMT and face-to-face groups. Patients with nonalcoholic fatty liver disease (NAFLD): Correction of lifestyle. When assessing the use of TMTs among NAFLD patients, a significant decrease in alanine aminotransferase and aspartate aminotransferase activity was found compared to that in face-to-face management. The results of the body mass index reduction are contradictory. The most pronounced tendency towards weight loss was observed with the telemedical follow-up of patients over a 6-month period. Patients with irritable bowel syndrome (IBS): Treatment and monitoring of symptoms. Two directions are distinguished in the treatment of IBS by ТМТs. The first is cognitive behavioral therapy (CBT). H. Everitt et al. showed clinically significant improvement in 72.8% of cases after 12 months of web-based CBT. The advantages of using telemedicine in the delivery of CBT include the geographical independence of the physician and the patient, personalization of treatment, and the possibility of ongoing support for the patient and his or her family. The second direction is the use of special diets, such as low-fermentable nutrient diets (FODMAP). Patients following the FODMAP diet supervised by the mobile app reduced symptom severity (odds ratio 55; 95% confidence interval 1198, p=0.01). Special mobile apps (IBS Constant Care) were used to monitor the condition of patients with IBS, which analyze input data and assess severity, providing information to both the patient and the physician. Patients with inflammatory bowel disease (IBD): Patient training and telemonitoring. The study by L. Pang et al. proved that the patients quality of life in the telemedicine intervention group was significantly higher (p=0.03). Another advantage of using TMTs is the provision of access to educational materials about IBD and the possibility of remote contact with the treating physician. The patients ability to obtain necessary information reduces the need for unplanned visits to medical facilities, thus reducing the cost of organizing medical care for patients with IBD. The degree of IBD activity and risk of recurrence and adherence to therapy did not differ significantly between the telemedicine intervention group and the standard face-to-face follow-up group. METHODS: A literature search relevant to the review was conducted in the PubMed database. The studies taken for assessment were those on the use of TMTs among patients with IBD, IBS, NAFLD, and CRC. TMTs were used to access educational information and dietary recommendations, provide information on lifestyle adjustments and physical activity, remind patients to take medicines, consult with physicians, and assess disease activity by completing online questionnaires. The various studies used text messaging, e-mail, mobile apps, websites, and videoconferencing apps as a means of communication. RESULTS: The use of telemedicine in the management of patients with digestive diseases showed high efficiency. TMTs contribute to: Improved quality of life in patients with digestive diseases. Increasing physical activity of patients with CRC and NAFLD. Improved quality of CRC screening. Maintaining remission of IBD and CRC as effectively as face-to-face monitoring. Moreover, the use of TMTs allows personalized treatment, ensures the ongoing support of the patient and his or her family by the medical staff, and provides patients with access to quality educational materials about the disease. CONCLUSIONS: Thus, the use of TMTs is promising in the treatment of digestive diseases and requires wider introduction into practice

Alteration of erythrocyte membrane polyunsaturated fatty acids in preterm newborns with retinopathy of prematurity

Projet OmegaROP.International audienceExtremely preterm infants are at high risk for retinopathy of prematurity (ROP), a potentially blinding disease characterized by abnormalities in retinal vascularization. Whereas animal studies revealed that n-3 polyunsaturated fatty acids (PUFAs) may be of benefit in preventing ROP, human studies conducted on preterm infants during the 1st weeks of life showed no association between blood n-3 PUFA bioavailability and ROP incidence and/or severity, probably because of the influence of nutrition on the lipid status of infants. In the OmegaROP prospective cohort study, we characterized the erythrocyte concentrations of PUFAs in preterm infants aged less than 29 weeks gestational age (GA) without any nutritional influence. We show that GA is positively associated with the erythrocyte n-6 to n-3 PUFA ratio, and particularly with the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA), in infants with ROP. A time-dependent accumulation of AA at the expense of DHA seems to occur in utero in erythrocytes of preterm infants who will develop ROP, thus reinforcing previous data on the beneficial properties of DHA on this disease. In addition, preliminary data on maternal erythrocyte membrane lipid concentrations suggest modifications in placental transfer of fatty acids. Documenting the erythrocyte AA to DHA ratio at birth in larger cohorts might be useful to set up new prognostic factors for ROP