Adaptive neurofuzzy ANFIS modeling of laser surface treatments

This paper introduces a new ANFIS adaptive neurofuzzy inference model for laser surface heat treatments based on the Green’s function. Due to its high versatility, efficiency and low simulation time, this model is suitable not only for the analysis and design of control systems, but also for the development of an expert real time supervision system that would allow detecting and preventing any failure during the treatment

Projection methods for large-scale T-Sylvester equations

The matrix Sylvester equation for congruence, or T-Sylvester equation, has recently attracted considerable attention as a consequence of its close relation to palindromic eigenvalue problems. The theory concerning T-Sylvester equations is rather well understood and there are stable and e cient numerical algorithms which solve these equations for small- to medium-sized matrices. However, developing numerical algorithms for solving large-scale T-Sylvester equations still remains an open problem. In this paper, we present several projection algorithms based on di erent Krylov spaces for solving this problem when the right-hand side of the T-Sylvester equation is a low-rank matrix. The new algorithms have been extensively tested, and the reported numerical results show that they work very well in practice, o ering a clear guidance on which algorithm is the most convenient in each situation.This work has been supported by Ministerio de Economía y Competitividad of Spain through grant MTM2012-32542.Publicad

Direct Sensitivity Analysis of Multibody Systems With Holonomic and Nonholonomic Constraints via an Index-3 Augmented Lagrangian Formulation With Projections

This is a post-peer-review, pre-copyedit version of an article published in Nonlinear Dynamics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11071-018-4306-y[Abstract] Optimizing the dynamic response of mechanical systems is often a necessary step during the early stages of product development cycle. This is a complex problem that requires to carry out the sensitivity analysis of the system dynamics equations if gradient-based optimization tools are used. These dynamics equations are often expressed as a highly nonlinear system of Ordinary Differential Equations (ODEs) or Differential-Algebraic Equations (DAEs), if a dependent set of generalized coordinates with its corresponding kinematic constraints is used to describe the motion. Two main techniques are currently available to perform the sensitivity analysis of a multibody system, namely the direct differentiation and the adjoint variable methods. In this paper, we derive the equations that correspond to the direct sensitivity analysis of the index-3 augmented Lagrangian formulation with velocity and acceleration projections. Mechanical systems with both holonomic and nonholonomic constraints are considered. The evaluation of the system sensitivities requires the solution of a Tangent Linear Model (TLM) that corresponds to the Newton-Raphson iterative solution of the dynamics at configuration level, plus two additional nonlinear systems of equations for the velocity and acceleration projections. The method was validated in the sensitivity analysis of a set of examples, including a five-bar linkage with spring elements, which had been used in the literature as benchmark problem for similar multibody dynamics formulations, a point-mass system subjected to nonholonomic constraints, and a full-scale vehicle model.Ministerio de Economía y Competitividad (MINECO); DPI2016-81005-PXunta de Galicia; ED431B2016/03

Behaviour of Augmented Lagrangian and Hamiltonian Methods for Multibody Dynamics in the Proximity of Singular Configurations

This is a post-peer-review, pre-copyedit version of an article published in Nonlinear Dynamics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11071-016-2774-5.[Abstract] Augmented Lagrangian methods represent an efficient way to carry out the forward-dynamics simulation of mechanical systems. These algorithms introduce the constraint forces in the dynamic equations of the system through a set of multipliers. While most of these formalisms were obtained using Lagrange's equations as starting point, a number of them have been derived from Hamilton's canonical equations. Besides being efficient, they are generally considered to be robust, which makes them especially suitable for the simulation of systems with discontinuities and impacts. In this work, we have focused on the simulation of mechanical assemblies that undergo singular configurations. First, some sources of numerical difficulties in the proximity of singular configurations were identified and discussed. Afterwards, several augmented Lagrangian and Hamiltonian formulations were compared in terms of their robustness during the forward-dynamics simulation of two benchmark problems. Newton-Raphson iterative schemes were developed for these formulations with the Newmark formula as numerical integrator. These outperformed fixed point iteration approaches in terms of robustness and efficiency. The effect of the formulation parameters on simulation performance was also assessed

A theoretical study on the mechanism of the base-promoted decomposition of N-chloro,N-methylethanolamine

The first step of the base-promoted decomposition of N-chloro,N-methylethanolamine in aqueous solution (CH3N(Cl)CH2CH2OH + HO- →imine + Cl- + H2O (+ CH2O)→amine + aldehyde) is investigated at the MP2/6-31++G(d,p) computing level. Solvation is included by using both a microsolvated model, in which two explicit water molecules simulate the specific solvent effects, and a hybrid cluster-continuum model, by applying a polarized continuum on the previous results, to account for the bulk effect of the solvent. Four alternative pathways (bimolecular fragmentation, Hofmann, Zaitsev and intramolecular eliminations) are possible for the rate-limiting step of this base-promoted decomposition. These reactive processes are bimolecular asynchronous concerted reactions. The common feature of the four pathways is the proton transfer to HO- being more advanced than all other molecular events, whereas imine formation is delayed. Non-reactive cyclic arrangements involving one of the explicit water molecules are found at transition structures of Hofmann and Zaitsev eliminations, such water molecule acting both as H+ donor and acceptor. Although MP2 calculations misjudge the absolute activation Gibbs free energy values, this computational level adequately predicts the enhancement in the decomposition rate due to the presence of the -OH grou

Effect of Ionizing Radiation on Human Myeloperoxidase: Reaction With Hydrated Electrons

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Myeloperoxidase (MPO) is a myeloid-lineage restricted enzyme largely expressed in the azurophilic granules of neutrophils. It catalyses the formation of reactive oxygen species, mainly hypochlorous acid, contributing to anti-pathogenic defense. Disorders in the production or regulation of MPO may lead to a variety of health conditions, mainly of inflammatory origin, including autoimmune inflammation. We have studied the effect of ionizing radiation on the activity of MPO, as measured by the capacity retained by the enzyme to produce hypochlorous acid as reactive oxygen species after exposure to successive doses of solvated electrons, the strongest possible one-e− reducing agent in water. Chlorination activity was still present after a very high irradiation dose, indicating that radiation damage does not take place at the active site, hindered in the core of MPO structure. Decay kinetics show a dependence on the wavelength, supporting that the process must occur at peripheral functional groups situated on external and readily accessible locations of the enzyme. These results are relevant to understand the mechanism of resistance of our innate anti-pathogenic defense system and also to get insight into potential strategies to regulate MPO levels as a therapeutic target in autoimmune diseases.This work was supported by: the Spanish Ministerio de Ciencia y Tecnología (CTQ2004-00534/BQU), the European Commission through the Access to Large-Scale Scientific Facilities Program (ref 41365), and the regional government of the Xunta de Galicia (Project GPC ED431B 2020/52)Xunta de Galicia; ED431B 2020/5

Did Patagonia collide with Gondwana in the Late Paleozoic? Some insights from a multidisciplinary study of magmatic units of the North Patagonian Massif

The origin of Patagonia and its relations with the South American crustal blocks to the north have been a matter of debate for decades. We report results from a multidisciplinary study centered on Paleozoic granitoids exposed in the northeastern corner of the North Patagonian Massif. Microstructural and magnetofabric studies reveal two suites of granitoids. Late Carboniferous (?) granitoids (Yaminué Complex, Tardugno Granodiorite, Cabeza de Vaca leucogranite) were emplaced and subsequently deformed in a major NNE-SSW compressive stress regime that also provoked top-to-the-SW thrust deformation in shallow crustal levels. Gravity and geobarometric studies show that the same major deformation event has been recorded at different crustal levels. The age and type of deformation of this event recorded across the northern boundary of Patagonia strongly supports a Late Carboniferous - Early Permian frontal collision between Patagonia and Gondwana. This major deformation event ceased by 281 Ma when the Navarrete Plutonic Complex, which shows mainly magmatic fabrics, was emplaced under a far-field WNW-ESE stress regime. Crustal continuity between the North Patagonian Massif and the Pampia and Arequipa- Antofalla terranes is suggested by similar Late Paleoproterozoic crustal model ages, comparable detrital zircon ages in Early Paleozoic successions, the apparent continuity of an Early Ordovician continental magmatic arc and paleomagnetic data. Reconciliation of this evidence with the Late Paleozoic frontal collision is obtained in a tectonic model that suggests that the North Patagonian Massif is a parautochthonous crustal block

Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody

Chronic Immune Activation in Systemic Lupus Erythematosus and the Autoimmune PTPN22 Trp620 Risk Allele Drive the Expansion of FOXP3+ Regulatory T Cells and PD-1 Expression.

In systemic lupus erythematosus (SLE), perturbed immunoregulation underpins a pathogenic imbalance between regulatory and effector CD4+ T-cell activity. However, to date, the characterization of the CD4+ regulatory T cell (Treg) compartment in SLE has yielded conflicting results. Here we show that patients have an increased frequency of CD4+FOXP3+ cells in circulation owing to a specific expansion of thymically-derived FOXP3+HELIOS+ Tregs with a demethylated FOXP3 Treg-specific demethylated region. We found that the Treg expansion was strongly associated with markers of recent immune activation, including PD-1, plasma concentrations of IL-2 and the type I interferon biomarker soluble SIGLEC-1. Since the expression of the negative T-cell signaling molecule PTPN22 is increased and a marker of poor prognosis in SLE, we tested the influence of its missense risk allele Trp620 (rs2476601C>T) on Treg frequency. Trp620 was reproducibly associated with increased frequencies of thymically-derived Tregs in blood, and increased PD-1 expression on both Tregs and effector T cells (Teffs). Our results support the hypothesis that FOXP3+ Tregs are increased in SLE patients as a consequence of a compensatory mechanism in an attempt to regulate pathogenic autoreactive Teff activity. We suggest that restoration of IL-2-mediated homeostatic regulation of FOXP3+ Tregs by IL-2 administration could prevent disease flares rather than treating at the height of a disease flare. Moreover, stimulation of PD-1 with specific agonists, perhaps in combination with low-dose IL-2, could be an effective therapeutic strategy in autoimmune disease and in other immune disorders

Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates.

OBJECTIVES: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. METHODS: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. RESULTS: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50-99% likelihood, and 4.0% (n = 203) to have a 10-49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. CONCLUSION: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability