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This paper presents a design proposal for the out-of-plane buckling resistance of prismatic beam-columns subject to axial compression and uniaxial major-axis bending that was developed based on the well-known Ayrton-Perry format. Firstly, the relevant theoretical background is summarized, closely following the theoretical derivation performed by Szalai and Papp (2010). Secondly, the required transformations for the engineering application of the design procedure are detailed and extended to arbitrary bending moment distributions. Appropriate generalized initial imperfection factors for the out-of-plane buckling of beam-columns are defined so as to achieving complete consistency across the stability verifications for columns, beams and beam-columns. The proposed procedure is subsequently validated against a large set of advanced numerical simulations. A good agreement was found between the numerical results and the estimates provided by the proposed design procedure, both in terms of the overall trend and the specific quantitative results. Based on a statistical assessment, the comparison with the interaction expression of Eurocode 3 (2005) (method 2) showed that this proposal slightly outperforms the Eurocode procedure, both in terms of average values and dispersion of results. [ABSTRACT FROM AUTHOR]

Rationale The role of macrophage iron in the physiopathology of atherosclerosis is an open question that needs to be clarified. In atherosclerotic lesions, recruited macrophages are submitted to cytokines and oxidized lipids which influence their phenotype. An important phenotypic population driven by oxidized phospholipids is the Mox macrophages which present unique biological properties but their iron phenotype is not well described. Objective To investigate the effect of Mox polarization by oxidized LDL (oxLDL) on macrophage iron metabolism in the absence or presence of proinflammatory stimuli. Methods Bone marrow-derived macrophages were treated with different sources of LDL and/or LPS/IFNγ (M1 activator). Expression of ferroportin ( Slc40a1 , alias Fpn ), heme oxygenase-1 ( Hmox1 ), H- and L-ferritin ( Fth1 and Ftl1 ), hepcidin ( Hamp ), ceruloplasmin ( Cp ) and interleukine-6 ( Il6 ) was followed by quantitative PCR. FPN and HMOX1 protein expression was analyzed by immunofluorescence and in-cell-Western blotting. Results Mox macrophages expressed increased Hmox1 and Fth1 levels with basal FPN protein levels despite the significant increase of Fpn mRNA. Upregulation of Hmox1 and Fpn mRNA was specific to LDL oxidative modification and mediated by NRF2. The downregulation of both Cp isoforms and the upregulation of Hamp expression observed in Mox macrophages suggest that FPN mediated iron export could be compromised. Simultaneous exposure to oxLDL and LPS/IFNγ leads to a mixed Mox/M1 phenotype that is closer to M1. Conclusion A microenvironment rich in oxLDL and proinflammatory cytokines could promote macrophage iron retention and lipid accumulation profiles, a specific cell phenotype that likely contributes to lesion development and plaque instability in atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: EC3 provides several methodologies for the stability verification of members and frames. Regarding tapered beam-columns, in EC3-1-1, the safety verification may be performed by the General Method. However, application of this method has been shown not to be reliable. On the other hand, the interaction formulae in EC3-1-1 were specifically calibrated for stability verification of prismatic members. Recently, Ayrton–Perry based proposals for the stability verification of web-tapered columns and beams, in line with the Eurocode principles for the stability verification of prismatic members, have shown to lead to a substantial increase of accuracy and to provide mechanical consistency relatively to application of the General Method. Such methodologies may be further applied to the existing interaction formulae. It is the purpose of this paper to propose a verification procedure for the stability verification of web-tapered beam-columns under in-plane loading by adaptation of the interaction formulae in EC3-1-1, validated through extensive FEM numerical simulations covering several combinations of bending moment about strong axis, My , and axial force, N, and levels of taper. [Copyright &y& Elsevier]

Abstract: Eurocode 3 provides several methods for the stability verification of members and frames. However, several inconsistencies and difficulties have been noticed in the case of non-uniform members regarding in what concerns stability verification. In this paper, the case of web-tapered beams is studied. In a first step, available methods for stability verification of web-tapered beams are discussed. A second order analytical model based on an Ayrton–Perry approach is then derived for the case of tapered beams with uniform bending moment and further extended to other bending moment distributions. Several consistent simplifications are carried out in order to build a simple but coherent design model for the stability verification of tapered beams subject to linear bending moment distributions and to parabolic bending moment. More than 3000 numerical simulations are carried out for calibration and analysis of the results. Throughout the paper, specific issues such as the presence of shear or the codified imperfections for welded cross-sections are brought in and taken into account. Finally, it is noted that the proposed model is consistent with recently proposed design models for the stability verification of prismatic beams. [Copyright &y& Elsevier]

Abstract: EC3–EN 1993-1-1 provides several methodologies for the stability verification of members and frames. When dealing with the verification of non-uniform members in general, with tapered cross-section, irregular distribution of restraints, non-linear axis, castellated, etc., the code mentions the possibility of carrying out a verification based on 2nd order theory; however, several difficulties are noted when doing so, in particular when the benefit of plasticity should be taken into consideration. Other than this, there are yet no guidelines on how to apply standardized, easily reproducible rules as those contained in Section 6.3.1 to 6.3.3 of the code to non-uniform members. As a result, practical safety verifications for these members are often carried out using conservative assumptions, not accounting for the advantages non-uniform members provide. In this paper, firstly, available approaches for the stability verification of non-uniform members are discussed. An Ayrton–Perry formulation is then derived for the case of non-uniform columns. Finally, and followed by a numerical parametric study covering a range of slenderness, cross-sections and fabrication process, a design proposal is made for the relevant case of in-plane flexural buckling of linearly tapered columns subject to constant axial force. The proposal is consistent with current rules for uniform columns provided in EC3-1-1, i.e., clause 6.3.1. [Copyright &y& Elsevier]

Abstract: Ceruloplasmin (CP) is a multicopper oxidase involved in the acute phase reaction to stress. Although the physiological role of CP is uncertain, its role in iron (Fe) homeostasis and protection against free radical-initiated cell injury has been widely documented. Previous studies showed the existence of two molecular isoforms of CP: secreted CP (sCP) and a membrane glycosylphosphatidylinositol (GPI)-anchored form of CP (GPI-CP). sCP is produced mainly by the liver and is abundant in human serum whereas GPI-CP is expressed in mammalian astrocytes, rat leptomeningeal cells, and Sertolli cells. Herein, we show using RT-PCR that human peripheral blood lymphocytes (huPBL) constitutively express the transcripts for both CP molecular isoforms previously reported. Also, expression of CP in huPBL is demonstrated by immunofluorescence with confocal microscopy and flow cytometry analysis using cells isolated from healthy blood donors with normal Fe status. Importantly, the results obtained show that natural killer cells have a significantly higher CP expression compared to all other major lymphocyte subsets. In this context, the involvement of lymphocyte-derived CP on host defense processes via its anti/prooxidant properties is proposed, giving further support for a close functional interaction between the immune system and the Fe metabolism. [Copyright &y& Elsevier]

In Eurocode 3 (2005) the buckling curve approach is adopted for verification of prismatic columns and beams. It has the flexibility of adjusting imperfection factors according to their sections, steel grade and other relevant parameters. However, for generic single members, built-up or not, uniform or not, with complex support conditions or not, the available possibilities for such cases are the General Method given in clause 6.3.4 of Eurocode 3 (2005) or advanced numerical simulations. The applicability of the general method, however, is limited and in some aspects inconsistent (Simões da Silva et al., (2010)). As an alternative, the stability of non-uniform members can be analysed using numerical GMNIA which is a time-consuming procedure and the output is highly dependent on the experience of the user. In this paper, a novel general formulation for stability design of steel columns, beams and beam-columns with variable geometry, loads and complex support conditions is presented. The verification is based on the buckling mode as shape of the initial imperfection with an amplitude previously calibrated for the standard prismatic simply-supported columns and beams in Eurocode 3. The verification is performed as an interaction equation where the first and second order contributions to the longitudinal stress utilization are added for each cross-section along the member length. Several aspects regarding the member behaviour in the context of a specific buckling mode are discussed and finally, validation of the approach is carried out to show its consistency and accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology. [Copyright &y& Elsevier]

Tapered steel members are often chosen instead of prismatic due to a better cross-section utilization along the member, which makes them an interesting and more economical alternative. Although EN1993-1-1 offers several methodologies for the stability verification of steel members and frames, it does not provide a clear guidance for the stability design of such members. Recently, the research group has provided simplified stability verification methodologies for tapered columns and beams. The developed methodologies are based on analytical derivations which were validated with advanced numerical simulations. In order to improve the accuracy of the proposed procedures, full-scale experimental tests on tapered columns, beams and beam-column were carried out. The experiments are used to calibrate a numerical model, incorporating all relevant parameters, such as: geometrical imperfections (local and global) and material imperfections (residual stresses). In this paper, firstly a global overview of the experimental programme on web-tapered steel members is given. The key results from each experiment are summarized; they are further used for the calibration of an advanced numerical model. [ABSTRACT FROM AUTHOR]

This paper presents the results of an experimental study on 12 m prestressed stayed columns. In total, 44 tests were carried out to investigate the compressive strength and behaviour of such systems by varying column cross-section geometry, diameter of cables, initial pretension level of stays and steel grade. The details of material testing for both steel and cable, and the compressive strength of each specimen including a detailed analysis of results for further numerical and analytical investigations are presented. The applicability of available analytical and design methods for determining the elastic buckling load and the load carrying capacity of stayed columns was assessed. The results provide detailed data on the behaviour of realistic PSSC and highlight the importance of the imperfections and the benefits of such systems. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder of still unknown etiology and the leading cause of dementia worldwide. Besides its main neuropathological hallmarks, a dysfunctional homeostasis of transition metals has been reported to play a pivotal role in the pathogenesis of this disease. Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at the level of cellular iron efflux. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this goal, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed in peripheral blood mononuclear cells (PBMCs) from 73 AD patients and 74 controls by quantitative PCR. The results obtained showed a significant decrease in the expression of aconitase 1 ( ACO1 ; P = 0.007); ceruloplasmin ( CP ; P < 0.001) and amyloid-beta precursor protein ( APP ; P = 0.006) genes in AD patients compared with healthy volunteers. These observations point out to a significant downregulation in the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients, when compared to controls. Taken together, these findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease. [ABSTRACT FROM AUTHOR]

In this study, an indoor/outdoor monitoring program was carried out in a gymnasium at the University of Leon, Spain. The main goal was a characterization of aerosol size distributions in a university gymnasium under different conditions and sports activities (with and without magnesia alba) and the study of the mass fraction deposited in each of the parts of the respiratory tract. The aerosol particles were measured in 31 discrete channels (size ranges) using a laser spectrometer probe. Aerosol size distributions were studied under different conditions: i) before sports activities, ii) activities without using magnesia alba, iii) activities using magnesia alba, iv) cleaning procedures, and v) outdoors. The aerosol refractive index and density indoors were estimated from the aerosol composition: 1.577–0.003i and 2.055 g cm − 3 , respectively. Using the estimated density, the mass concentration was calculated, and the evolution of PM 1 , PM 2.5 and PM 10 for different activities was assessed. The quality of the air in the gymnasium was strongly influenced by the use of magnesia alba (MgCO 3 ) and the number of gymnasts who were training. Due to the climbing chalk and the constant process of resuspension, average PM 10 concentrations of over 440 μg m − 3 were reached. The maximum daily concentrations ranged from 500 to 900 μg m − 3 . Particle size determines the place in the respiratory tract where the deposition occurs. For this reason, the inhalable, thoracic, tracheobronchial and respirable fractions were assessed for healthy adults and high risk people, according to international standards. The estimations show that, for healthy adults, up to 300 μg m − 3 can be retained by the trachea and bronchi, and 130 μg m − 3 may reach the alveolar region. The different physical activities and the attendance rates in the sports facility have a significant influence on the concentration and size distributions observed. [ABSTRACT FROM AUTHOR]