Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Wider reinforced masonry shear walls subjected to cyclic lateral loading

Partially grouted wider reinforced masonry wall, built predominantly with the use of face shell bedded hollow concrete blocks, is adopted extensively in the cyclonic areas due to its economy. Its out-of-plane response to lateral pressure loading is well definied; however its in-plane shear behaviour is less well understood, in particular it is unclear how the grouted reinforced cores affect the load paths within the wall. For the rational design of the walls, clarification is sought as to whether the wall acts as a composite of unreinforced panels surrounded by the reinforced cores or simply as a continuum embedded with reinforcement at wider spacing. This paper reports four full scale walls tested under in-place cyclic shear loading to provide some insight into the effect of the grout cores in altering the load paths within the wall. The global lateral load - lateral deflection hysteretic curves as well as the local responses of some critical zones of the shear walls are presented. It is shown that the aspect ratio of the unreinforced masonry panels surrounded by the reinforced grouted cores within the shear walls have profound effect in ascertaining the behaviour of the shear walls.

Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones : a possible pathological role in subchondral bone sclerosis

Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeo-stasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, im-munohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the os-teocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogene-sis.

Improved design rules for hollow flange sections subject to lateral distortional buckling

The LiteSteel Beam (LSB) is a new hollow flange section with a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. It is subjected to lateral distortional buckling when used as flexural members, which reduces its member moment capacity. An investigation into the flexural behaviour of LSBs using experiments and numerical analyses led to the development of new design rules for LSBs subject to lateral distortional buckling. However, the comparison of moment capacity results with the new design rules showed that they were conservative for some LSB sections while slightly unconservative for others due to the effects of section geometry. It is also unknown whether these design rules are applicable to other hollow flange sections such as hollow flange beams (HFB). This paper presents the details of a study into the lateral distortional buckling behaviour of hollow flange sections such as LSBs, HFBs and their variations. A geometrical parameter defined as the ratio of flange torsional rigidity to the major axis flexural rigidity of the web (GJf/EIxweb) was found to be a critical parameter in evaluating the lateral distortional buckling behaviour and moment capacities of hollow flange sections. New design rules were therefore developed by using a member slenderness parameter modified by K, where K is a function of GJf/EIxweb. The new design rules based on the modified slenderness parameter were found to be accurate in calculating the moment capacities of not only LSBs and HFBs, but also other types of hollow flange sections.

Numerical modelling and design of LiteSteel Beams subject to lateral buckling

The LiteSteel Beam (LSB) is a new hollow flange channel section developed using a patented dual electric resistance welding and cold-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a slender web, and is commonly used as flexural members. However, the LSB flexural members are subjected to a relatively new lateral distortional buckling mode, which reduces their moment capacities. Unlike lateral torsional buckling, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist and cross sectional change due to web distortion. Therefore a detailed investigation into the lateral buckling behaviour of LSB flexural members was undertaken using experiments and finite element analyses. This paper presents the details of suitable finite element models developed to simulate the behaviour and capacity of LSB flexural members subject to lateral buckling. The models included all significant effects that influence the ultimate moment capacities of such members, including material inelasticity, lateral distortional buckling deformations, web distortion, residual stresses, and geometric imperfections. Comparison of elastic buckling and ultimate moment capacity results with predictions from other numerical analyses and available buckling moment equations, and experimental results showed that the developed finite element models accurately predict the behaviour and moment capacities of LSBs. The validated model was then used in a detailed parametric study that produced accurate moment capacity data for all the LSB sections and improved design rules for LSB flexural members subject to lateral distortional buckling.

Numerical method for predicting the elastic lateral distortional buckling moment of a mono-symmetric beam with web openings

When used as floor joists, the new mono-symmetric LiteSteel beam (LSB) sections require web openings to provide access for inspections and various services. The LSBs consist of two rectangular hollow flanges connected by a slender web, and are subjected to lateral distortional buckling effects in the intermediate span range. Their member capacity design formulae developed to date are based on their elastic lateral buckling moments, and only limited research has been undertaken to predict the elastic lateral buckling moments of LSBs with web openings. This paper addresses this research gap by reporting the development of web opening modelling techniques based on an equivalent reduced web thickness concept and a numerical method for predicting the elastic buckling moments of LSBs with circular web openings. The proposed numerical method was based on a formulation of the total potential energy of LSBs with circular web openings. The accuracy of the proposed method’s use with the aforementioned modelling techniques was verified through comparison of its results with those of finite strip and finite element analyses of various LSBs.

Behaviour and design of cold-formed steel beams subject to lateral-torsional buckling

Cold-formed steel beams are increasingly used as floor joists and bearers in buildings. Their behaviour and moment capacities are influenced by lateral-torsional buckling when they are not laterally restrained adequately. Past research on lateral-torsional buckling has concentrated on hot-rolled steel beams. Hence a numerical study was undertaken to investigate the lateral-torsional buckling behaviour of simply supported cold-formed steel lipped channel beams subjected to uniform bending. For this purpose a finite element model was developed using ABAQUS and its accuracy was verified using available numerical and experimental results. It was then used in a detailed parametric study to simulate the lateral-torsional buckling behaviour and capacity of cold-formed steel beams under varying conditions. The moment capacity results were compared with the predictions from the current design rules in many cold-formed steel codes and suitable recommendations were made. European design rules were found to be conservative while Australian/New Zealand and North American design rules were unconservative. Hence the moment capacity design equations in these codes were modified in this paper based on the available finite element analysis results. This paper presents the details of the parametric study, recommendations to current design rules and the new design rules proposed in this research for lateral-torsional buckling of cold-formed steel lipped channel beams.

Elastic lateral buckling of cantilever LiteSteel beams under transverse loading

The LiteSteel Beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using its patented dual electric resistance welding and automated continuous roll-forming technologies. The LSB has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. Its flexural strength for intermediate spans is governed by lateral distortional buckling characterised by simultaneous lateral deflection, twist and web distortion. Recent research on LSBs has mainly focussed on their lateral distortional buckling behaviour under uniform moment conditions. However, in practice, LSB flexural members are subjected to non-uniform moment distributions and load height effects as they are often under transverse loads applied above or below their shear centre. These loading conditions are known to have significant effects on the lateral buckling strength of beams. Many steel design codes have adopted equivalent uniform moment distribution and load height factors based on data for conventional hot-rolled, doubly symmetric I-beams subject to lateral torsional buckling. The non-uniform moment distribution and load height effects of transverse loading on cantilever LSBs, and the suitability of the current design modification factors to include such effects are not known. This paper presents a numerical study based on finite element analyses of the elastic lateral buckling strength of cantilever LSBs subject to transverse loading, and the results. The applicability of the design modification factors from various steel design codes was reviewed, and suitable recommendations are presented for cantilever LSBs subject to transverse loading.

Numerical study of cold-formed steel beam subject to lateral-torsional buckling

The use of cold-formed steel members as structural columns and beams in residential, industrial and commercial buildings has increased significantly in recent times. This study is focused on the use of cold-formed steel sections as flexural members subject to lateral-torsional buckling. For this purpose a finite element model of a simply supported lipped channel beam under uniform bending was developed, validated using available numerical and experimental results, and used in a detailed parametric study. The moment capacity results were then compared with the predictions from the current ambient temperature design rules in the cold-formed steel structures codes of Australia, New Zealand, North America and Europe. European design rules were found to be conservative while Australian and American design rules were unsafe. This paper presents the results of the numerical study, the comparison with the current design rules and the new proposed design rules.

Lateral torsional buckling behaviour of cold-formed steel beams at elevated temperatures

Abstract: This paper presents the details of a study into the behaviour and moment capacities of cold-formed steel lipped channel beams (LCB) subject to lateral-torsional buckling at elevated temperatures. It was based on a validated numerical model of a simply supported and laterally unrestrained LCB subjected to a uniform moment. The ultimate moment capacities from this study were compared with the predicted values using ambient and fire design methods. This study showed that the lateral torsional buckling capacity is strongly influenced by the level of non-linearity in the stress-strain curves of steel at elevated temperatures. Hence most of the current design methods based on a single buckling curve were not adequate to determine the moment capacities. This paper proposes a new design method for the cold-formed steel LCBs subject lateral-torsional buckling at elevated temperatures.