Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents

Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel^®.     

Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory,Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts’ integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice’s hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by “rejuvenating” the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.     

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.     

Effective Natural Killer Cell Degranulation Is an Essential Key in COVID-19 Evolution

NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.     

Prediction of Losses in Flow Through the Last Stage of LP Steam Turbine

The aim of presented work was the prediction of the losses in the wet steam flow through the last stage of 200MW steam turbine LP part.To this end,three numerical tools were used.The first method was the streamline curvature method (SCM) used on the meridional plane with losses correlations.The next two methods,TASCflow commercial CFD code and an in-house CFD code,based on the solution of the Reynolds- averaged Navier-Stokes equations (RANS).Ap- plication of three independent numerical tools al- lowed to make the more reliable losses analysis and made possible to compare applied numerical methods with each other. For the flow modeling in the last stage of LP steam turbine the various two-phase flow models were used and compared.The equilibrium model and non-equi- librium models with homogeneous and/or heterogeneous condensation were considered.The boundary conditions at the inlet and outlet from the stage were selected in such way to get the beginning of the homogeneous condensation process in the sta- tot.It corresponded to the part load of the turbine, i.e.140MW power and pressure in condenser 2.7kPa.     

Static output-feedback control under information structure constraints

An important challenge in the static output-feedback control context is to provide an isolated gain matrix possessing a zero–nonzero structure, mainly in problems presenting information structure constraints. Although some previous works have contributed some relevant results to this issue, a fully satisfactory solution has not yet been achieved up to now. In this note, by using a Linear Matrix Inequality approach and based on previous results given in the literature, we present an efficient methodology which permits us to obtain an isolated static output-feedback gain matrix having, simultaneously, a zero–nonzero structure imposed a priori.     

A semantic role labelling-based framework for learning ontologies from Spanish documents

Currently, most of the information available in the Web is adapted primarily for human consumption, but there is so much information that can no longer be processed by a person in a reasonable time, either in digital or physical formats. To solve this problem, the idea of the Semantic Web arose. The Semantic Web deals with adding machine-readable information to Web pages. Ontologies represent a very important element of this web, as they provide a valid and robust structure to represent knowledge based on concepts, relations, axioms, etc. The need for overcoming the bottleneck provoked by the manual construction of ontologies has generated several studies and research on obtaining semiautomatic methods to learn ontologies. In this sense, this paper proposes a new ontology learning methodology based on semantic role labeling from digital Spanish documents. The method makes it possible to represent multiple semantic relations specially taxonomic and partonomic ones in the standardized OWL 2.0. A set of experiments has been performed with the approach implemented in educational domain that show promising results.     

Control of attendance applied in higher education through mobile NFC technologies

This paper presents an improved attendance control system, required for continuous evaluation which has become compulsory following the Bologna Process. It provides a solution based on NFC technology and is based on a real project developed and pilot tested at the “Universidad Pontificia de Salamanca, Campus Madrid”.     

Efficient implementation of the implicit error correction nVoD schema

Implicit Error Correction is a near Video-on-Demand (nVoD) schema that trades bandwidth utilization for initial playback delay while potentially allowing an infinite number of users. Additionally, it provides error protection without further bandwidth increase by exploiting the implicit redundancy of nVoD protocols, using linear combinations of the segments transmitted in a given time slot. This paper introduces a new implementation that outperforms the original schema by adding two new mechanisms: redundancy channels and feedback error correction.     

Emptiness and Finiteness for Tree Automata with Global Reflexive Disequality Constraints

In recent years, several extensions of tree automata have been considered. Most of them are related with the capability of testing equality or disequality of certain subterms of the term evaluated by the automaton. In particular, tree automata with global constraints are able to test equality and disequality of subterms depending on the state to which they are evaluated. The emptiness problem is known decidable for this kind of automata, but with a non-elementary time complexity, and the finiteness problem remains unknown. In this paper, we consider the particular case of tree automata with global constraints when the constraint is a conjunction of disequalities between states, and the disequality predicate is forced to be reflexive. This restriction is significant in the context of XML definitions with monadic key constraints. We prove that emptiness and finiteness are decidable in triple exponential time for this kind of automata.