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Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments. Multiomic brain tissue analysis identified sex-specific molecular changes in Amyotrophic lateral sclerosis (ALS), revealing subgroups within the disease and pointing to the MAPK pathway as an early disease mechanism and potential therapeutic target. [ABSTRACT FROM AUTHOR]

Corrosion of steel reinforcement is known to affect the residual bearing capacity of the structure. The loss of metal supposes a decrease of the sectional area of the reinforcing bar, either homogeneously distributed or concentrated in some zones. The morphology of the corroded area is a critical issue because while the uniform loss is influencing the steel strength, when it is localized also the ductility is reduced due the local stress concentration. There are previous publications showing the impact of corrosion on some mechanical aspects of the steel as on the ductility, the strength or the elastic modulus, but still we lack of a comprehensive framework of all types of corrosion. In this work a classification is made of the types of damages for better assessing their consequences. Further, through application of basic classical mechanics are given expressions to calculate the "corrosion factor" related to the yield strength, the ultimate strength, the elastic modulus and the elongation (ductility). Finally, through fracture mechanics and an energetic approach are given the expressions for the critical stress intensity factor and the "apparent" residual section "loss" of the corroded steel bars. [ABSTRACT FROM AUTHOR]

The effect of traffic vibrations on buildings is of special interest as its sources have multiplied becoming a concern for residents or for those who work, visit or preserve buildings of heritage value. The problem has their origin in characteristics such as the deterioration of the roads or concentration of public transport routes in adjacent streets. The effect of these vibrations has been the object of study in recent years, with works referred to especially experimental determinations, whose results can be used to assess whether the measurements obtained are within accepted values by some regulations. These results can also be used to calibrate global numerical models to determine this influence analyzing attenuation measures. This paper proposes a global model of finite elements that allows dealing with the treatment of traffic-induced vibrations in structures and analyzing an alternative of solution according to the location. The model includes the building under study, land and surrounding constructions to have orientative results of the whole including its boundary conditions. The actions caused by the traffic are established through impulses that define the load states to be applied. Finally, an alternative is proposed to analyze the options to mitigate the effect of the generated vibrations. [ABSTRACT FROM AUTHOR]

In simplified seismic structural analyses, not all the deterioration modes are adequately considered. This work discusses the relation among the hidden failure modes of columns of non-ductile reinforced concrete building frames and their global collapse mechanism. With this aim, a numerically efficient model is developed and implemented in OpenSEES. Two benchmark problems are analyzed with this model: the well-known Van Nuys Hotel and a prototype building designed for gravity loads only; in this last case, the results are compared with experiments on a one-third scale model. The obtained results confirm that simplified models grossly overestimate the building capacity. [ABSTRACT FROM AUTHOR]

The main objective of this article is to achieve a very high lift rotor to take the maximum advantage of the kinetic energy of a slow velocity water flow, which belongs to a lowland river type. Low speed flux and lack of depth are the main obstacles in hydrokinetic operation. The use of a high lift aerodynamic profile and the gain of the rotor number of blades serve to accomplish the task. This work presents the fluid dynamic design for an axial hydrokinetic turbine rotor, studied in a three-dimensional (3D) numerical simulation by means of Computational Fluid Dynamics (CFD). The use of CFD techniques avoids some physical model assays. For the hydrokinetic turbine rotor design, first a onedimensional (1D) theoretical design was carried out, starting with the selection of a suitable airfoil profile to create the hydrofoil blade. Then, the 3D rotor geometry was defined and studied carefully by means of CFD, to check its hydrodynamic behavior, that is, lift and drag, streamline velocities and pressure fields. The CFD results were obtained using an open CFD code (Kratos). [ABSTRACT FROM AUTHOR]

The seismic behavior of a representative medium-rise building of Mexico City is evaluated using the capacity spectrum method. This method is widely used in the seismic assessment of buildings because it allows obtaining fragility curves which permit evaluating the ability of a building to resist earthquakes. A real full-height multistory model is proposed to test the capabilities of the algorithm exhibited. The model is outlined through structural drawings sized and structured in accordance with building code regulations for masonry structures in Mexico City. Computational requirements for the analysis of large structures are indicated in addition to improvements to a nonlinear computing code for better performance in terms of memory management and execution times. Finally, a comparison of obtained results and building code regulations is carried out, highlighting differences in the obtained results. The need to handle meshes with a high number of finite elements (FEs) led to development of a new layered finite element that can reproduce the nonlinear behavior of its constituent materials when there are out-of-plane stresses without having to introduce additional degrees of freedom. The proposed FE is compared with the standard FE, presenting different kinematics, and excellent results are obtained. This work emerges from the need to combine and improve existing technologies in the field of finite-element analysis. One such technology is the numerical simulation of the behavior of composite materials. Therefore, it was also necessary to develop a computing program capable of reading both finite-element meshes and patterns of fibers to calculate the information of the composite materials, such as volumetric participation and fiber's orientation. [ABSTRACT FROM AUTHOR]

The continuous increase of computational capacity has encouraged the extensive use of multiscale techniques to simulate the material behaviour on several fields of knowledge. In solid mechanics, the multiscale approaches which consider the macro-scale deformation gradient to obtain the homogenized material behaviour from the micro-scale are called first-order computational homogenization. Following this idea, the second-order FE2 methods incorporate high-order gradients to improve the simulation accuracy. However, to capture the full advantages of these high-order framework the classical boundary value problem (BVP) at the macro-scale must be upgraded to high-order level, which complicates their numerical solution. With the purpose of obtaining the best of both methods i.e. first-order and second-order, in this work an enhanced-first-order computational homogenization is presented. The proposed approach preserves a classical BVP at the macro-scale level but taking into account the high-order gradient of the macro-scale in the micro-scale solution. The developed numerical examples show how the proposed method obtains the expected stress distribution at the micro-scale for states of structural bending loads. Nevertheless, the macro-scale results achieved are the same than the ones obtained with a first-order framework because both approaches share the same macro-scale BVP. [ABSTRACT FROM AUTHOR]

The behavior of reinforced concrete structures under severe demands, as strong ground motions, is highly complex; this is mainly due to the complexity of concrete behavior and to the strong interaction between concrete and steel, with several coupled failure modes. On the other hand, given the increasing awareness and concern on the worldwide seismic risk, new developments have arisen in earthquake engineering; nonetheless, some developments are mainly based on simple analytical tools that are widely used, given their moderate computational cost. This research aims to provide a solid basis for validation and calibration of such developments by using computationally efficient continuum mechanics-based tools. Within this context, this paper presents a model for 3D simulation of cyclic behavior of RC structures. The model integrates a bond-slip model developed by one of the authors and the damage variable evolution methodology for concrete damage plastic model developed by some authors. In the integrated model, a new technique is derived for efficient 3D analysis of bond-slip of 2 or more crossing reinforcing bars in beam-column joints, slabs, footings, pile caps, and other similar members. The analysis is performed by implementing the bond-slip model in a user element subroutine of Abaqus and the damage variable evolution methodology in the original concrete damage plastic model in the package. Two laboratory experiments consisting of a column and a frame subjected to cyclic displacements up to failure are simulated with the proposed formulation. [ABSTRACT FROM AUTHOR]

The construction of confined masonry buildings has become a good choice to meet the housing needs of low-income families in big cities. Despite this, current building codes for such construction allow the use of highly simplified analysis techniques that have hardly changed in the last 40 years. This paper is based on numerical simulation and discusses the need to combine and improve existing techniques in finite-element method (FEM) analysis for composite materials, to assess the overall structural behavior of reinforced concrete structures with masonry in-fills, and consequently to support the derivation of rational rules for analysis and design. Through the use of a simple yet powerful shell finite element (FE), state-of-the-art theories of mixtures to analyze composite materials, a computational tool to generate the volume fraction of composites, and the Mexican building code, this paper attempts to be a guide to numerical reproduction of the overall behavior of confined masonry structures. [ABSTRACT FROM AUTHOR]

In engineering, traditional approaches aimed at teaching concepts of dynamics to engineering students include the study of a dense yet sequential theoretical development of proofs and exercises. Structural dynamics are seldom taught experimentally in laboratories since these facilities should be provided with expensive equipment such as wave generators, data-acquisition systems, and heavily wired deployments with sensors. In this paper, the design of an experimental experience in the classroom based upon digital fabrication and modeling tools related to structural dynamics is presented. In particular, all experimental deployments are conceived with low-cost, open-source equipment. The hardware includes Arduino-based open-source electronics whereas the software is based upon object-oriented open-source codes for the development of physical simulations. The set of experiments and the physical simulations are reproducible and scalable in classroom-based environments. [ABSTRACT FROM AUTHOR]

A new damage model, based on continuum damage mechanics and simulating the opening, closing, and reopening of cracks in concrete using only one surface of discontinuity, is proposed in this article. The model complies with the thermodynamics principles of nonreversible, isothermal, and adiabatic processes. Two scalar internal variables have been defined: a tensile damage variable d+ and a compressive damage variable d-; the threshold of damage is controlled by only one surface of discontinuity and a new parameter controlling the damage variable that should be activated. This new parameter represents the ratio of tensile stress to compressive stress in the damaged material. The continuity of response under complex loads, which is one of the aims of this work, is ensured. An adequate response under different types of loads leads to the conclusion that the proposed model provides a powerful tool to numerically analyze reinforced concrete structures. Validation and illustrative examples are included in the article. [ABSTRACT FROM AUTHOR]

This article presents the formulation of an enriched macro finite element based on the trigonometric shear deformation theory for the static analysis of symmetrically laminated composite plates. Shear correction factor is not required because this theory accounts for tangential stress-free boundary conditions on the plate boundary surfaces. The macro element is obtained using the principle of virtual work and Gram-Schmidt orthogonal polynomials as enrichment functions. The implementation of the obtained algorithm is simple and efficient, and allows studying general quadrilateral plates with a single macro element. Several examples are presented to show the capability and applicability of the developed formulation. [ABSTRACT FROM PUBLISHER]

A new generalized damage model for quasi-incompressible hyperelasticity in a total Lagrangian finite-strain framework is presented. A Kachanov-like reduction factor (1 − D) is applied on the deviatoric part of the hyperelastic constitutive model. Linear and exponential softening are defined as damage evolution laws, both describable in terms of only two material parameters. The model is formulated following continuum damage mechanics theory such that it can be particularized for any hyperelastic model based on the volumetric-isochoric split of the Helmholtz free energy. However, in the present work, it has been implemented in an in-house finite element code for neo-Hooke and Ogden hyperelasticity. The details of the hybrid formulation used are also described. A couple of three-dimensional examples are presented to illustrate the main characteristics of the damage model. The results obtained reproduce a wide range of softening behaviors, highlighting the versatility of the formulation proposed. The damage formulation has been developed to be used in conjunction with mixing theory in order to model the behavior of fibered biological tissues. As an example, the markedly different behaviors of the fundamental components of the rectus sheath were reproduced using the damage model, obtaining excellent correlation with the experimental results from literature. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper investigates the possibility of using classical first order computational homogenization together with a simple regularization procedure based on the fracture energy of the micro-scale-constituents. A generalized geometrical characteristic length takes into account the size of the macro-scale element as well as the size of the RVE (and its constituents). The proposed regularization ensures objectivity of the dissipated energy at the macro-scale, with respect to the size of the FE in both scales and with respect to the size of the RVE. The proposed method is first validated against benchmark examples, and finally applied to the numerical simulation of experimental tests on in-plane loaded shear walls made of periodic masonry. [ABSTRACT FROM AUTHOR]

The knowledge of contact forces in teeth surfaces during mastication or para-functional movements can help to understand processes related to friction and wear of human dental enamel. The development of a numerical model for analysis of the occlusal contact between two antagonistic teeth is proposed, which includes three basic steps: the characterisation of the surface roughness, its homogenisation using an assumed distribution function and the numerical determination of the resulting forces. Finite element strain results for the main different asperities are statistically combined, deriving the predicted macroscopic behaviour of the interface. Axisymmetric and 3D numerical models with an elasto-plastic constitutive law are used to simulate micro-indentations and micro-contacts, respectively. The contact is allowed to occur locally in planes not necessarily parallel to the surface's mean plane, a problem for which there is no analytical solution. The three identified parameters, homogenised surface hardness (3.68 GPa), surface yield stress (3.08 GPa) and static friction coefficient (0.23), agree with the experimental values reported in the literature. [ABSTRACT FROM PUBLISHER]

Mechanical factors such as stresses and strains play a major role in the growth and remodelling of soft biological tissues. The main constituents of tissue undergo different processes reacting to mechanical stimulus. Thereby, the characterisation of growth and remodelling requires an accurate estimation of the stresses and strains of their main components. Many soft tissues can be considered as composite materials and can be analysed using an appropriate rule of mixtures. Particularly, arterial tissue can be modelled as an isotropic soft matrix reinforced with preferentially oriented collagen fibres. An inverse approach to obtain the mechanical characterisation of each main component is proposed in this work. The procedure is based on a rule of mixtures raised in a finite deformation framework and generalised to include kinematics and compatibility equations for serial–parallel behaviour. This methodology allows obtaining the stress–strain relationship of the components fitting experimental data. [ABSTRACT FROM PUBLISHER]

This paper presents a variational formulation for the free vibration analysis of unsymmetrically laminated composite plates with elastically restrained edges. The study includes a micromechanics approach that allows starting the study considering each layer as constituted by long unidirectional fibers in a continuous matrix. The Mori-Tanaka method is used to predict the mechanical properties of each lamina as a function of the elastic properties of the components and of the fiber volume fraction. The resulting mechanical properties for each lamina are included in a general Ritz formulation developed to analyze the free vibration response of thick laminated anisotropic plates resting on elastic supports. Comprehensive numerical examples are computed to validate the present method, and the effects of the different mechanical and geometrical parameters on the dynamical behavior of different laminated plates are shown. New results for general unsymmetrical laminates with elastically restrained edges are also presented. The analytical approximate solution obtained in this paper can also be useful as a basis to deal with optimization problems under, for instance, frequency constraints. [ABSTRACT FROM AUTHOR]

This paper reviews the most common formulations to obtain the compression strength of long fiber composites due to fiber buckling. This failure mode was first studied by Rosen (Fibre Composite Materials, pp. 37–45, 1965) who defined two different fiber buckling modes, extensional and transverse. Further studies improved the first model proposed by Rosen by defining with more accuracy the mechanics of the problem. Although each formulation use a different approach to solve the problem, all of them agree in the dependence of fiber buckling on three main parameters: matrix shear strength, fiber initial misalignments and volumetric participation of the fibers in the composite. Once having described the different approaches used, and the parameters on which they depend, this paper describes a new formulation capable of obtaining the compression strength of composites taking into account the fiber buckling phenomenon. This formulation uses the serial/parallel mixing theory developed by Rastellini et al. (Comput. Struct. 86(9):879–896, 2008) to simulate the composite, and takes advantage of knowing the mechanical performance of the composite constituents to simulate the fiber buckling phenomenon. This is done with an homogenization procedure. It consists in introducing the interaction between fibers and matrix into their respective constitutive equations. The interaction between fiber and matrix takes into account fiber initial misalignments, its volumetric participation and the mechanical properties of both constituents. The new formulation proposed is implemented in a finite element code, taking into account that fibers can have different misalignment levels, and that the composite behaves differently if it is under tensile or compression forces. The mechanical performance of the formulation proposed is studied with several finite element simulations of compressed composites. Finally, the correctness of the formulation is proved by comparing the numerical results with the experimental tests provided by Barbero and Tomblin (Int. J. Solids Struct. 33(29):4379–4393, 1996), Tomblin et al. (Int. J. Solids Struct. 34(13):1667–1679, 1997). [ABSTRACT FROM AUTHOR]

This work presents the results of a study carried out to characterize the mechanical response of a high damping rubber to be used in designing and constructing energy dissipating devices and base isolators for controling strong vibrations in civil engineering structures. A new parametric model of the elastomer is proposed to be employed in the design procedure and structural analysis of passive controlled structures. The parameters of the model are calibrated using experimental data obtained from tests on rubber specimens under different loading paths. The main dissipating energy mechanisms of the rubber are identified. The proposed model is able to reproduce those main mechanisms as well as geometric second order effects such as tension stiffening due to the effect of axial strains in the response. The response predicted by the proposed model is compared with that obtained from experimental tests and from the Kelvin and plasticity models. [ABSTRACT FROM AUTHOR]