2. Universidad Cardenal Herrera-CEU

This document aims to make a retrospective of our work in the Ford research group in collaboration with researchers from the CEU Cardenal Herrera University and the University of Valencia. The research group originated from the doctoral thesis by Eduardo García Magraner and his thesis was directed by Nicolás Montés in 2016. The Mini-terms were formulated for the first time in this thesis. From then on, the research group grew as the mini-terms began to consolidate both industrially and scientifically. At industrial level we were provided with a CDTI (Centre for the Development of Industrial Technology) which made it possible to massify the mini-terms at Ford factory in Valencia and at scientific level we attended different congresses. Especially relevant was ICINCO 2018 since the concept of the mini-terms could be presented to the programme chair of the congress, Oleg Gusikhin, (Global Data Insight & Analytics, Ford Motor Company, United States). His support led to the consolidation of the mini-terms through their standardization within Ford and also the consolidation of the group through the inclusion of the CEU Cardenal Herrera University in the URP (University Research Program). The success of Eduardo García’s doctoral thesis motivated the Foundation for Development and Innovation (FDI) to decide to fund doctoral theses within Ford, financing a thesis in collaboration with the University of Valencia and another one with the CEU Cardenal Herrera University. Moreover, Eduardo García’s thesis motivated the staff of the plant to take the step to carry out doctoral theses, funded by the INNODOCTO programme of the Generalitat Valenciana. Throughout this journey different awards have been won such as the Henry Ford Technology Awards in 2019, the Factories of the Future Awards in 2021, the Global Manufacturing Technical Excellence Award in 2023 and the Angel Herrera Award for the best research work in 2024. Twenty-four communications have been made to congresses, ICINCO being the congress with the highest number of communications. In particular, at ICINCO 2020, one of these articles was selected as the Best Industrial Paper Award. Thirteen articles have been published in indexed journals with an impact index and also three book chapters. This document aims at reviewing the different tools and concepts developed and introduced by the research group as well as trying to define its objective.

The progressive emergence of antimicrobial resistance has become a global health problem in need of rapid solution. Research into new antimicrobial drugs is imperative. Drug repositioning, together with computational mathematical prediction models, could be a fast and efficient method of searching for new antibiotics. The aim of this study was to identify compounds with potential antimicrobial capacity against Escherichia coli from US Food and Drug Administration-approved drugs, and the similarity between known drug targets and E. coli proteins using a topological structure-activity data analysis model. This model has been shown to identify molecules with known antibiotic capacity, such as carbapenems and cephalosporins, as well as new molecules that could act as antimicrobials. Topological similarities were also found between E. coli proteins and proteins from different bacterial species such as Mycobacterium tuberculosis, Pseudomonas aeruginosa and Salmonella Typhimurium, which could imply that the selected molecules have a broader spectrum than expected. These molecules include antitumor drugs, antihistamines, lipid-lowering agents, hypoglycemic agents, antidepressants, nucleotides, and nucleosides, among others. The results presented in this study prove the ability of computational mathematical prediction models to predict molecules with potential antimicrobial capacity and/or possible new pharmacological targets of interest in the design of new antibiotics and in the better understanding of antimicrobial resistance.

In recent days there are many possibilities in develop solutions for industrial manufacturing process thanks to the emerging technology based in Industry 4.0, where one can measure and manage data from an industrial process in real time been able to know more information than ever before from the process. But still having challenges in complex process where monitoring data and give a solution is less intuitive, mostly due to a complex physical definition of the process and manufacturing car body parts in automotive is a clear example. In deep drawing process is common to have variations in the process parameters and they can carry out bad manufactured parts. The cycle time, the robust process and the complex physics in the process are the main problems to obtain feasible information from the process. In the following it is proposed a new methodology to have full knowledge of the process applying the so-called method Hybrid Twin.

Quinolones are one of the most extensively used therapeutic families of antibiotics. However, the increase in antibiotic-resistant bacteria has rendered many of the available compounds useless. After applying our prediction model of activity against E. coli to a library of 1000 quinolones, two quinolones were selected to be synthesized. Additionally, a series of zwitterionic quinolonates were also synthesized. Quinolones and zwitterionic quinolonates were obtained by coupling the corresponding amine with reagent 1 in acetonitrile. Antibacterial activity was assessed using a microdilution method. All the compounds presented antibacterial activity, especially quinolones 2 and 3, selected by the prediction model, which had broad-spectrum activity. Furthermore, a new type of zwitterionic quinolonate with antibacterial activity was found. These compounds can lead to a new line of antimicrobials, as the structures, and, therefore, their properties, are easily adjustable in the amine in position 4 of the pyridine ring.

Currently, the development of resistance of Enterobacteriaceae bacteria is one of the most important health problems worldwide. Consequently, there is a growing urge for finding new compounds with antibacterial activity. Furthermore, it is very important to find antibacterial compounds with a good pharmacokinetic profile too, which will lead to more efficient and safer drugs. In this work, we have mathematically described a series of antibacterial quinolones by means of molecular topology. We have used molecular descriptors and related them to various pharmacological properties by using multilinear regression (MLR) analysis. The regression functions selected by presenting the best combination of a number of quality and validation metrics allowed for the reliable prediction of clearance (CL), and minimum inhibitory concentration 50 against Enterobacter aerogenes (MIC50Ea) and Proteus mirabilis (MIC50Pm). The obtained results clearly reveal that the combination of molecular topology methods and MLR provides an excellent tool for the prediction of pharmacokinetic properties and microbiological activities in both new and existing compounds with different pharmacological activities.

Post-processing meshing algorithms are widely used to achieve the desired quality in quadrilateral meshes. Assuming that the mesh quality depends on the distortion and the size error of each of its convex quadrilaterals, deficiencies arise by considering solutions based in minimizing either the distortion or the size error. To solve this undesirable situation, in this paper we propose a new smoothing post-processing meshing algorithm. This procedure provides a good compromise between the distortion and the size of each element in the mesh. It is formulated by using an elasticity-based argument and allows to be implemented either in sequential or parallel form. Moreover, it provides a good quality output compared with some of the usual smoothing post-processing meshing algorithms.

Solutions of partial differential equations can exhibit multiple time scales. Standard discretization techniques are constrained to capture the finest scale to accurately predict the response of the system. In this paper, we provide an alternative route to circumvent prohibitive meshes arising from the necessity of capturing fine-scale behaviors. The proposed methodology is based on a time-separated representation within the standard Proper Generalized Decomposition, where the time coordinate is transformed into a multi-dimensional time through new separated coordinates, each representing one scale, while continuity is ensured in the scale coupling. For instance, when considering two different time scales, the governing Partial Differential Equation is commuted into a nonlinear system that iterates between the so-called microtime and macrotime, so that the time coordinate can be viewed as a 2D time. The macroscale effects are taken into account by means of a finite element-based macro-discretization, whereas the microscale effects are handled with unidimensional parent spaces that are replicated throughout the time domain. The resulting separated representation allows us a very fine time discretization without impacting the computational efficiency. The proposed formulation is explored and numerically verified on thermal and elastodynamic problems.

The present paper aims at analyzing the topological content of the complex trajectories that weeder-autonomous robots follow in operation. We will prove that the topological descriptors of these trajectories are affected by the robot environment as well as by the robot state, with respect to maintenance operations. Most of existing methodologies enabling efficient diagnosis are based on the data analysis, and in particular on some statistical quantities derived from the data. The present work explores the use of an original approach that instead of analyzing quantities derived from the data, analyzes the “shape” of the data, that is, the time series topology based on the homology persistence. We will prove that this procedure is able to extract valuable patterns able to discriminate the trajectories that the robot follows depending on the particular patch in which it operates, as well as to differentiate the robot behavior before and after undergoing a maintenance operation. Even if it is a preliminary work, and it does not pretend to compare its performances with respect to other existing technologies, this work opens new perspectives in considering quite natural and simple descriptors based on the intrinsic information that data contains, with the aim of performing efficient diagnosis and prognosis.

Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry—many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry–virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.

In this paper, we propose a new splitting algorithm for dynamical low-rank approximation motivated by the fibre bundle structure of the set of fixed rank matrices. We first introduce a geometric description of the set of fixed rank matrices which relies on a natural parametrization of matrices. More precisely, it is endowed with the structure of analytic principal bundle, with an explicit description of local charts. For matrix differential equations, we introduce a first order numerical integrator working in local coordinates. The resulting algorithm can be interpreted as a particular splitting of the projection operator onto the tangent space of the low-rank matrix manifold. It is proven to be exact in some particular case. Numerical experiments confirm this result and illustrate the robustness of the proposed algorithm.