2. Universidad Cardenal Herrera-CEU

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.

Oxidative stress is associated with multiple pathologies such as cancer and can exacerbate the development of them. In this work, we have studied the antioxidant capacity of 5-Fluorouracile (5-FU) which is an antineoplastic drug that is used in the treatment of colorectal cancer. 5-FU is a compound that has a chemical structure similar to uracil and is also fluorinated. New fluorinated derivates previously obtained in our laboratory were tested to study its antioxidant activity. All the compounds analyzed were able to inhibit lipid peroxidation when used in concentrations of 10 μM.

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.

Since its emergence in March 2020, the SARS-CoV-2 global pandemic has produced more than 116 million cases and 2.5 million deaths worldwide. Despite the enormous efforts carried out by the scientific community, no effective treatments have been developed to date. We applied a novel computational pipeline aimed to accelerate the process of identifying drug repurposing candidates which allows us to compare three-dimensional protein structures. Its use in conjunction with two in silico validation strategies (molecular docking and transcriptomic analyses) allowed us to identify a set of potential drug repurposing candidates targeting three viral proteins (3CL viral protease, NSP15 endoribonuclease, and NSP12 RNA-dependent RNA polymerase), which included rutin, dexamethasone, and vemurafenib. This is the first time that a topological data analysis (TDA)-based strategy has been used to compare a massive number of protein structures with the final objective of performing drug repurposing to treat SARS-CoV-2 infection.