115 research outputs found
Diffusion study of 15N implanted into α-Ti using the nuclear resonance technique
No full textThe diffusion of 15 N in a-Ti was studied in the 673-1023 K temperature range by using ion implantation and nuclear resonance techniques. The measurements show that the diffusion coefficients follow an Arrhenius behaviour D(T) = D0 exp (-Q/RT) where D0 = (1.1 ± 0.8) x 10-7 m2 s-1 and Q = (183 ± 2) kJ/mol. A comparison with previous results is also given.Fil: Bregolin, F. L.. Universidade Federal do Rio Grande do Sul; BrasilFil: Behar, M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Dyment, Fanny. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Get PDFMultiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
Quiescent bone lining cells are a major source of osteoblasts during adulthood
No full textThe in vivo origin of bone-producing osteoblasts is not fully defined. Skeletal stem cells, a population of mesenchymal stem cells resident in the bone marrow compartment, are thought to act as osteoprogenitors during growth and adulthood. Quiescent bone lining cells (BLCs) have been suggested as a population capable of activation into mature osteoblasts. These cells were defined by location and their morphology and studies addressing their significance have been hampered by their inaccessibility, and lack of markers that would allow for their identification and tracing. Using lineage tracing models, we have observed labeled osteoblasts at time points extending beyond the reported lifespan for this cell type, suggesting continuous reactivation of BLCs. BLCs also make a major contribution to bone formation after osteoblast ablation, which includes the ability to proliferate. In contrast, mesenchymal progenitors labeled by Gremlin1 or alpha smooth muscle actin do not contribute to bone formation in this setting. BLC activation is inhibited by glucocorticoids, which represent a well-established cause of osteoporosis. BLCs express cell surface markers characteristic of mesenchymal stem/progenitors that are largely absent in osteoblasts including Sca1 and Leptin Receptor. BLCs also show different gene expression profiles to osteoblasts, including elevated expression of Mmp13, and osteoclast regulators RANKL and macrophage colony stimulating factor, and retain osteogenic potential upon transplantation. Our findings provide evidence that bone lining cells represent a major source of osteoblasts during adulthood.Igor Matic, Brya G. Matthews, Xi Wang, Nathaniel A. Dyment, Daniel L. Worthley, David W. Rowe, Danka Grcevic, Ivo Kalajzi
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Get PDFUsing the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals
Spatial differences in the distribution of leads in the ice cover in the Atlantic sector of the Arctic basin
Get PDFWe analyzed data on the spatial distribution (density) of large breaks (gaps) in the drifting sea ice cover in the Western Arctic for the period from October 2005 to September 2017, obtained through decoding of lowresolution images from the NOAA satellites. The specific length of gaps, which is the total length of them over an area of 1 km2, is used as a characteristic of the spatial density. It was found that along the continental slope, approximately from the meridian 70° E to the Lincoln Sea, there is a well-defined area of high density, which remains throughout most part of the ice cycle. In this area, the values of the specific gap length averaged over two-month periods exceeded 24 m/km2. In the near-polar region, the density of breaks was smaller throughout the whole ice cycle. The least values of the specific length take place in May–June that is caused by changes in the general state of the ice cover. It was determined that the density of gaps in this area of the Arctic basin well correlated with the speed of wind drift of ice: the more intensive the drift, the larger the density. On the continental slope, two local zones with maximum values of the specific length of breaks reaching 32 m/km2 are considered. It is suggested that the stability of their location in space and time is connected with the increased influence of tidal processes on the deformation of the ice cover over local bottom elevations on the continental slope. A correlation between the bottom profile and the values of the specific length of the gaps along two conditional lines passing through the maximum value zones did show that the largest values of the density are noticed in areas with significant gradients of the depth
Grounds for movement: Green school grounds as sites for promoting physical activity
No full textAn environmental factor of particular importance to children's physical activity levels appears to be the presence of parks and open space. Thus, in promoting children's health, school grounds merit consideration as a potential setting for intervention. This paper explores how 'green' school grounds, which contain a greater diversity of landscaping and design features, affect the quantity and quality of physical activity among elementary school children. Teachers, parents and administrators associated with 59 schools across Canada completed questionnaires (n = 105). Analysis reveals that through greening, school grounds diversify the play repertoire, creating opportunities for boys and girls of all ages, interests and abilities to be more physically active. Complementing the rule-bound, competitive games supported by asphalt and turf playing fields, green school grounds invite children to jump, climb, dig, lift, rake, build, role play and generally get moving in ways that nurture all aspects of their health and development. Of particular significance is the potential to encourage moderate and light levels of physical activity by increasing the range of enjoyable, non-competitive, open-ended forms of play at school. Seen in this light, green school grounds stand to be an important intervention to be included in school health promotion initiatives. © The Author 2007. Published by Oxford University Press. All rights reserved
Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA
No full textIn genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this pa- per, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection
Breaks in the Arctic ice cover: from observations to predictions
No full textBreaks (ruptures) and cracks is the distinguishing feature of any ice cover in the Arctic seas during the cold season and in the whole Arctic Basin throughout a year. The formation of them is a consequence of macro-deformation of the ice thickness. Investigating of the ice breaking in the Arctic begins with single visual observations during the ice aerial surveys in the 1940s and continues till nowadays using regular information from artificial Earth satellites. Processing of big volumes of satellite data and creating climatological datasets on breaks became possible owing to the development of algorithms for automatic identification of the ice breaks in images. Interpretation of the satellite images is based on the fundamental difference between physical properties of breaks and the surrounding consolidated ice. Algorithms for automatic recognition of ruptures using satellite data obtained in different wavelength ranges, including the use of artificial intelligence, are currently being developed. The main characteristics of breaks which are usually analyzed are as follows: the summarized area of them and its ratio to the total area of the ice field, the mean and maximum widths as well as the total length. The temporal and spatial variability of these characteristics is also considered. Such information is needed for solving problems of improving models of ice cover dynamics and modeling the interaction between the ocean and the atmosphere at high latitudes. A specific feature of publications of the Russian authors on this topic is the practical use of the results obtained for hydrometeorological support of navigation in ice. For the navigation purposes, the dominant orientation of the ruptures on the way of ships is of greatest importance. Operational and prognostic information about the orientation and extent of ruptures, including distribution of them in an ice field are the key data for choosing the optimal sailing route in the Arctic
Length of large leads in drifting ice of the sub-Atlantic part of the Arctic Basin with the use of satellite images
Get PDFData on the extent of the large discontinuities of drifting ice in the Western part of the Arctic basin are ana‑ lyzed for the period from October 2005 to September 2012. The data were obtained as a result of decoding the low resolution images received from the NOAA satellites. Areas with the low, medium and high lengths of the leads were isolated. It was found that, during the entire ice cycle, areas with low lengths (less than 100 km) were the most numerous. Definite seasonal as well as inter‑annual variations were also determined in the changes of repeatability of the lead lengths in the ice cover, its relative value and the average values. They are manifested in changes of the mentioned parameters being calculated for both, the whole set of leads, and separately from data within each of the isolated areas. The seasonal variations of these parameters are shown to be consistent with the well‑known intra‑annual changes in the state of drifting ice, consisting in the development of the process of ice formation from October to March, and the subsequent destruction of the ice fields in April–June. Fluctuations with duration up to five years were revealed within the inter‑annual changes of characteristics of the lengths of leads. The presence of these inter‑annual changes may be explained by the development of the processes leading to «weakening» of drifting ice during the period under consideration. The assumption that the fluctuations in the length of discontinuities of the ice were related to the changes of the rate of the ice drift is grounded
Protein-protein interaction analysis highlights additional loci of interest for multiple sclerosis
Get PDFGenetic factors play an important role in determining the risk of multiple sclerosis (MS). The strongest genetic association in MS is located within the major histocompatibility complex class II region (MHC), but more than 50 MS loci of modest effect located outside the MHC have now been identified. However, the relative candidate genes that underlie these associations and their functions are largely unknown. We conducted a protein-protein interaction (PPI) analysis of gene products coded in loci recently reported to be MS associated at the genome-wide significance level and in loci suggestive of MS association. Our aim was to identify which suggestive regions are more likely to be truly associated, which genes are mostly implicated in the PPI network and their expression profile. From three recent independent association studies, SNPs were considered and divided into significant and suggestive depending on the strength of the statistical association. Using the Disease Association Protein-Protein Link Evaluator tool we found that direct interactions among genetic products were significantly higher than expected by chance when considering both significant regions alone (p<0.0002) and significant plus suggestive (p<0.007). The number of genes involved in the network was 43. Of these, 23 were located within suggestive regions and many of them directly interacted with proteins coded within significant regions. These included genes such as SYK, IL-6, CSF2RB, FCLR3, EIF4EBP2 and CHST12. Using the gene portal BioGPS, we tested the expression of these genes in 24 different tissues and found the highest values among immune-related cells as compared to non-immune tissues (p<0.001). A gene ontology analysis confirmed the immune-related functions of these genes. In conclusion, loci currently suggestive of MS association interact with and have similar expression profiles and function as those significantly associated, highlighting the fact that more common variants remain to be found to be associated to MS
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