Monitoring of northern climate exposure

Currently, facility managers are faced with many advanced decisions regarding when and how to inspect, maintain, repair or renew existing facilities in a costeffective manner. The evolution of the deteriorations of road structures in reinforced concrete depends on the exposure of the elements to water in liquid form or vapour and to other aggressive agents such as chloride. Current models of ionic transport neglect the effect of real ionic concentration in contact with concrete structures, it means boundary conditions are considered with simple tendency as uniform concentration during the winter period and model parameters are derived from the fitting method. Therefore, it implies in ineffective prediction models of deterioration, i.e. steel rebar corrosion by chloride presence or carbonation, alkali-granular reaction, acid attacks, etc. Structure are sensitive to their environment and their interaction with it is directly related to the processes of deterioration. The degradation of structures exposed to salt-laden mist is faster in the wetter areas. On the contrary, the deterioration of the structures caused by salt spray in the drier zone is slower. The structures, exposed to splashing (precipitation, wind, splash, etc.), have a slower rate of degradation in the wetter regions. The amount of rain has an indirect effect in the process of deterioration of the structure exposed to salt-laden mist because it changes the contact time of chloride on the surface of the structures. For this purpose, a unique exposure monitoring was developed. This mobile station, named MExStUL, contains an atmospheric sensor and new possibilities of chloride detection contained in splashes, mist and static water near the road improving the real exposure of structure and the boundary conditions. First results highlight the real influence of environmental parameters on structures durability on highways. Salt concentration is not uniform during winter period and water thickness demonstrate important periods of drying

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer

Background: Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. Methods: We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. Results: We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Conclusions: Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC

Infant head growth in male siblings of children with and without autism spectrum disorders

Previous research has indicated that children with autism exhibit accelerated head growth (HG) in infancy, although the timing of acceleration varies between studies. We examined infant HG trajectory as a candidate autism endophenotype by studying sibling pairs. We retrospectively obtained serial head orbitofrontal circumference measurements of: a) 48 sibling pairs in which one (n = 28) or both (n = 20) sibs were affected by an autism spectrum disorder (ASD); and b) 85 control male sibling pairs. Rate of HG of ASD subjects was slightly accelerated compared to controls, but the magnitude of difference was below the limit of reliability of standard measurement methods. Sibling intra class correlation for rate of HG was highly statistically significant; the magnitude was significantly stronger among autism-affected families (ICC = .63) than among controls (ICC = .26), p < .01. Infant HG trajectory appears familial—possibly endophenotypic—but was not a reliable marker of autism risk among siblings of ASD probands in this sample

An Integrated Meta-Analysis of Two Variants in HOXA1/HOXB1 and Their Effect on the Risk of Autism Spectrum Disorders

BACKGROUND: HOXA1 and HOXB1 have been strongly posed as candidate genes for autism spectrum disorders (ASD) given their important role in the development of hindbrain. The A218G (rs10951154) in HOXA1 and the insertion variant in HOXB1 (nINS/INS, rs72338773) were of special interest for ASD but with inconclusive results. Thus, we conducted a meta-analysis integrating case-control and transmission/disequilibrium test (TDT) studies to clearly discern the effect of these two variants in ASD. METHODS AND FINDINGS: Multiple electronic databases were searched to identify studies assessing the A218G and/or nINS/INS variant in ASD. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. A total of 10 and 7 reports were found to be eligible for meta-analyses of A218G and nINS/INS variant, respectively. In overall meta-analysis, the pooled OR for the 218G allele and the INS allele was 0.97 (95% CI = 0.76-1.25, P(heterogeneity) = 0.029) and 1.14 (95% CI = 0.97-1.33, P(heterogeneity) = 0.269), respectively. No significant association was also identified between these two variants and ASD risk in stratified analysis. Further, cumulative meta-analysis in chronologic order showed the inclination toward null-significant association for both variants with continual adding studies. Additionally, although the between-study heterogeneity regarding the A218G is not explained by study design, ethnicity, and sample size, the sensitive analysis indicated the stability of the result. CONCLUSIONS: This meta-analysis suggests the HOXA1 A218G and HOXB1 nINS/INS variants may not contribute significantly to ASD risk

Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release

Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not

Actions microclimatique et environnementale des ouvrages d'art routier [Microclimatic and environmental actions of road structures]

Les différentes zones d’un ouvrage d’art routier sont étudiées en fonction de leur degré d’exposition au microclimat environnant. Les conditions climatiques provenant de stations météorologiques et la cinétique des véhicules permettent de définir des zones d’exposition aux produits salants et au climat. Une division judicieuse d’un ouvrage en éléments structuraux en fonction de son exposition permet de prendre en considération l’importante variabilité spatiale et de définir des zones de sensibilité équivalente face aux détériorations. Sur la base de stations météorologiques suisses, d’un monitoring d’un ouvrage d’art routier, d’enquêtes auprès des autorités publiques, de mesures ponctuelles in situ et de recherches bibliographiques, cet article met en exergue le microclimat des structures de manière précise. Cette approche permet de définir les différentes zones d’exposition des ouvrages, à savoir les zones de brouillard salin, d’éclaboussures et de stagnation d’eau et de définir l’importance du microclimat en vue de prédire l’évolution des détériorations des structures. -- Various areas of a highway structure are studied regarding their level of exposure to the surrounding microclimate. Climate conditions from meteorological stations and vehicle kinetics are used to determine zones that are exposed to salt products and climate. Dividing a highway into structural elements based on exposure takes into account the significant spatial variation and helps define zones of equivalent sensitivity to deteriorations. Based on Swiss meteorological stations, highway structure monitoring, inquiries with public authorities, in situ spot measuring and literature surveys, this article precisely highlights the microclimate of these structures. This approach can help define the various exposure areas of the structures, namely salt mist, splash and water stagnation areas as well as determine the significance of the microclimate in order to predict the evolution of structural deteriorations

"In vitro" binding of cellular, alpha-amanitin sensitive, RNA polymerase to infectious, mengovirus-induced double-stranded RNA

A cellular, α-Amanitin sensitive, RNA polymerase from mouse L cells binds “in vitro” to Mengovirus-induced, double-stranded (ds) RNA. Formation of the “enzyme-ds RNA” complex was studied by the nitrocellulose filter technique. Reaction strongly depends on K+/(NH)++ and Mn++/Mg++ concentration, occurs optimally at 37°C, is linear with time up to 10 minutes, and is inhibited by a rifamycin derivative AF/013. Competition experiments demonstrated that neither heat-denatured Mengovirus RF nor single-stranded ribonucleotides interfere with complex formation, whereas the double-helical form same RNAs (native RF, Poly I:C; Poly A:U) efficiently compete with Mengovirus RF for cellular polymerase. These results seem to indicate that the double-helical nature of the template is essential for binding to occur