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Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that primarily affects motor neurons and is accompanied by sustained unregulated immune responses, but without clear indications of the ultimate causative mechanisms. The identification of a diverse array of ALS phenotypes, a series of recently discovered mutations, and the links between ALS and frontotemporal degeneration have significantly increased our knowledge of the disease. In this review we discuss the main features involved in ALS pathophysiology in the context of recent advances in 'omics' approaches, including genomics, proteomics, and others. We emphasize the pressing need to combine clinical imaging with various different parameters taken from omics fields to facilitate early, accurate diagnosis and rational drug design in the treatment of ALS. ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that affects motor neurons. There is no cure for ALS. Although ALS is a brain disease closely related to Parkinson's, Alzheimer's, and Huntington's diseases, so far the complex descriptions of ALS-associated damage have not clarified the ultimate causative mechanisms.Current interventions are the result of unintentional discoveries or the non-specific application of cell-based therapies whose effects are not completely understood. However, research on ALS is currently thriving and the body of knowledge on the subject has increased remarkably in recent years.The emergence of functional immunomics for ALS from established omics technologies are opening new therapeutic avenues based on the smart manipulation of the immune system.Molecular imaging in the field of ALS is evolving. Thus, a combination of omics technologies and clinical imaging may very well be the key for breaking-down ALS., Financial support was provided by grants AI075285 and AI093903 from the US National Institutes of Health, RG4111A1 and JF2161-A-5 from the National Multiple Sclerosis Society, and PA0069 from the International Progressive MS Alliance (F.J.Q.), the Regional Ministry of Economy, Science and Innovation (P11-CTS-8161 to D.P.), the Regional Ministry of Health (PI13-575 to S.L.), the PAIDI Program from the Andalusian Government (CTS-677 to D.P.), and the Spanish Ministry of Economy and Competitiveness with FEDER co-funding (PI14-1600 to D.P.; SAF-2012-39720 and CP10-00527 to C.R.). D.C-H. holds a postdoctoral fellowship from CONACyT (Mexico). M.C-G. holds a PIF-University of Seville PhD fellowship.

In this work, Valanis model parameters, and their variation with bolt preload, were determined for a bolted lap joint, which consisted in two steel plates held together by a metric 12 screw. For this purpose, a series of transitory non-linear analyses were performed on the basis of a three dimensional finite element model of the bolted lap joint subjected to varying bolt preloads and tangential displacements. Curve fitting of hysteresis cycles obtained from numerical simulations allowed determination of Valanis model parameters as well as assessment of bolt preload influence on these parameters. In addition, the present numerical simulations provided information about the evolution of the contact state from stick to slip regimes between the bolted plates, reflecting the non-linear behaviour of the joint. Quasi-static tests at several preloads and tangential displacements conditions were conducted to validate Valanis model parameters previously obtained from numerical simulations. The present findings provided detailed information about the evolution of the aforementioned Valanis parameters with bolt preload. Thus, we confirmed that equivalent stiffness values corresponding to the macro-slip regime as well as the upper limit of the sticking regime (Et and σ0, respectively) are highly influenced by bolt preload levels. These results may prove useful to appropriately design bolted joints to be used under specific stiffness and damping criteria, and therefore reducing the vibration response of the joint., This work has been funded with project MYCT/FEDER Ref. BIA2006-15266-C02-02, and by Diputación General de Aragón (Grant no. G.C.I.A. 2011.T67).