Novel Stereoselective Transformations under Lewis Base Catalysis

295 p.Dada la necesidad de las empresas farmacéuticas de comercializar compuestos enantioméricamente puros, la síntesis de moléculas enantiopuras ha atraído mucho interés en los últimos años. La síntesis asimétrica y en concreto, la organocatálisis, constituyen hoy en día uno de los principales métodos para la obtención de compuestos enantioméricamente puros. Este tipo de catálisis emplea una gran variedad de organocatalizadores que pueden clasificarse en función de su modo de activación en ácidos de Brønsted, bases de Brønsted, ácidos de Lewis y bases de Lewis. El trabajo recogido en esta memoria se centra en el uso de bases de Lewis para promover transformaciones novedosas en el ámbito de la síntesis asimétrica. Así, se han empleado aminas secundarias quirales para llevar a cabo la reacción de reagrupamiento vinilciclopropano-ciclopenteno enantioselectiva de manera efectiva. Por otro lado, mediante la activación del bis(pinacolato)diboro a través de bases de Lewis y su reactividad frente a alenilamidas, se ha desarrollado una reacción de hidroborilación regioselectiva de alenilamidas a través de la cual se ha podido acceder a olefinas trisustituidas empleadas como ¿building blocks¿ en futuras transformaciones. Además, como parte de una estancia predoctoral, se incluye el trabajo realizado en el grupo de investigación del Prof. Nuno Maulide en la Universidad de Viena el cual se centra en el campo de laactivación de amidas mediante el uso de anhídrido tríflico.Ministerio de Economía y Competitividad beca predoctoral de formación de personal investigador” (BES-2015-072454). Gobierno Vasco por la subvención a grupos de investigación IT328-10 e IT908-16 Universidad del País Vasco UPV/EHU proyecto EHUA 12/09 y MICINN (CTQ2014-52107-P y CTQ2017-83633-P

Novel Stereoselective Transformations under Lewis Base Catalysis

295 p.Dada la necesidad de las empresas farmacéuticas de comercializar compuestos enantioméricamente puros, la síntesis de moléculas enantiopuras ha atraído mucho interés en los últimos años. La síntesis asimétrica y en concreto, la organocatálisis, constituyen hoy en día uno de los principales métodos para la obtención de compuestos enantioméricamente puros. Este tipo de catálisis emplea una gran variedad de organocatalizadores que pueden clasificarse en función de su modo de activación en ácidos de Brønsted, bases de Brønsted, ácidos de Lewis y bases de Lewis. El trabajo recogido en esta memoria se centra en el uso de bases de Lewis para promover transformaciones novedosas en el ámbito de la síntesis asimétrica. Así, se han empleado aminas secundarias quirales para llevar a cabo la reacción de reagrupamiento vinilciclopropano-ciclopenteno enantioselectiva de manera efectiva. Por otro lado, mediante la activación del bis(pinacolato)diboro a través de bases de Lewis y su reactividad frente a alenilamidas, se ha desarrollado una reacción de hidroborilación regioselectiva de alenilamidas a través de la cual se ha podido acceder a olefinas trisustituidas empleadas como ¿building blocks¿ en futuras transformaciones. Además, como parte de una estancia predoctoral, se incluye el trabajo realizado en el grupo de investigación del Prof. Nuno Maulide en la Universidad de Viena el cual se centra en el campo de laactivación de amidas mediante el uso de anhídrido tríflico.Ministerio de Economía y Competitividad beca predoctoral de formación de personal investigador” (BES-2015-072454). Gobierno Vasco por la subvención a grupos de investigación IT328-10 e IT908-16 Universidad del País Vasco UPV/EHU proyecto EHUA 12/09 y MICINN (CTQ2014-52107-P y CTQ2017-83633-P

An Approach to Data Analysis in 5G Networks

5G networks expect to provide significant advances in network management compared to traditional mobile infrastructures by leveraging intelligence capabilities such as data analysis, prediction, pattern recognition and artificial intelligence. The key idea behind these actions is to facilitate the decision-making process in order to solve or mitigate common network problems in a dynamic and proactive way. In this context, this paper presents the design of Self-Organized Network Management in Virtualized and Software Defined Networks (SELFNET) Analyzer Module, which main objective is to identify suspicious or unexpected situations based on metrics provided by different network components and sensors. The SELFNET Analyzer Module provides a modular architecture driven by use cases where analytic functions can be easily extended. This paper also proposes the data specification to define the data inputs to be taking into account in diagnosis process. This data specification has been implemented with different use cases within SELFNET Project, proving its effectiveness.Depto. de Ingeniería de Software e Inteligencia Artificial (ISIA)Fac. de InformáticaTRUEUnión Europea. Horizonte 2020pu

Molecular-Level Insight into Charge Carrier Transport and Speciation in Solid Polymer Electrolytes by Chemically Tuning Both Polymer and Lithium Salt

The advent of Li-metal batteries has seen progress toward studies focused on the chemical modification of solid polymer electrolytes, involving tuning either polymer or Li salt properties to enhance the overall cell performance. This study encompasses chemically modifying simultaneously both polymer matrix and lithium salt by assessing ion coordination environments, ion transport mechanisms, and molecular speciation. First, commercially used lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt is taken as a reference, where F atoms become partially substituted by one or two H atoms in the −CF3 moieties of LiTFSI. These substitutions lead to the formation of lithium(difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI) and lithium bis(difluoromethanesulfonyl)imide (LiDFSI) salts. Both lithium salts promote anion immobilization and increase the lithium transference number. Second, we show that exchanging archetypal poly(ethylene oxide) (PEO) with poly(ε-caprolactone) (PCL) significantly changes charge carrier speciation. Studying the ionic structures of these polymer/Li salt combinations (LiTFSI, LiDFTFSI or LiDFSI with PEO or PCL) by combining molecular dynamics simulations and a range of experimental techniques, we provide atomistic insights to understand the solvation structure and synergistic effects that impact macroscopic properties, such as Li+ conductivity and transference number.The authors acknowledge support from the European Commission grant for Erasmus Mundus Joint Master’s Degree MESC+ under Framework Agreement Number 2018-1424/001-001-EMJMD, the EU Marie Sklodowska-Curie COFUND DESTINY project under Grant Agreement No. 945357, and the Basque Government PhD Grant. H.M. acknowledges funding from the “Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco” (Grant IT1358-22). They also thank SGI/IZO-SGIker UPV/EHU for supercomputing resources

CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma

CD229 is a cell-surface molecule predominantly expressed on lymphocytes. Its expression in B-cell malignancies is poorly known. We tested the presence of this immunoreceptor on a large number of malignancies and normal tissue using a new monoclonal antibody and tissue microarrays. Our data show that CD229 expression is restricted to hematopoietic cells. It was strongly expressed in myeloma and marginal-zone lymphomas. Because of the high expression on multiple myeloma cells, we also analyze the presence of soluble CD229 in the sera of these patients. We showed that serum levels of soluble CD229 in myeloma patients, at the time of diagnosis, could be useful as a prognostic biomarker. Altogether, our results indicate that CD229 represents not only a useful disease biomarker but also an attractive therapeutic target. CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC). In this study, we used a new mAb against the cytoplasmic region of CD229 to study the expression of CD229 on normal tissues and B-cell malignancies, including multiple myeloma (MM), using tissue microarrays. We showed CD229 to be restricted to hematopoietic cells. It was strongly expressed in all cases of MM and in most marginal-zone lymphomas (MZL). Moderate CD229 expression was also found in chronic lymphocyte leukemia (CLL), follicular (FL), classic mantle-cell (MCL) and diffuse large B-cell lymphoma. Given the high expression on myeloma cells, we also analyzed for the presence of soluble CD229 in the sera of these patients. Serum levels of soluble CD229 (sCD229) at the time of diagnosis in MM patients could be useful as a prognostic biomarker. In conclusion, our results indicate that CD229 represents not only a useful biomarker but also an attractive therapeutic target

Staging Parkinson’s Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life

COPPADIS Study Group.[Introduction] In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient’s quality of life (QoL) with regard to a defined clinical stage.[Materials and Methods] Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale.[Results] A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; ).[Conclusion] The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.Peer reviewe

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

COPPADIS Study Group.[Background and Objective] Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group.[Material and Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable).[Results] After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865).[Conclusions] Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.This research was funded by Fundación Española de Ayuda a la Investigación en Parkinson y otras Enfermedades Neuro-degenerativas (Curemos el Parkinson; www.curemoselparkinson.org).Peer reviewe

Síntesis de catalizadores orgánicos : síntesis de organocatalizadores quirales basados en la estructura de BINOL

Retirado a solicitud el al autoraSe define como quiralidad a la propiedad de un objeto de no ser superponible con su imagen especular. Así, cuando una molécula posee dicha propiedad , surgen dos isómeros configuracionales conocidos como enantiómeros . A la mezcla 1:1 de enantiómeros se le llama mezcla racémica o racemato y se caracteriza por no ser ópt icamente activa . Ambos enantiómeros presentes en la mezcla tienen las mismas propiedades físicas y químicas a excepción de su actividad óptica , aunque su comportamiento frente a dianas biológicas puede variar dependiendo del enantiómer

Towards Incidence Management in 5G Based on Situational Awareness

The fifth generation mobile network, or 5G, moves towards bringing solutions to deploying faster networks, with hundreds of thousands of simultaneous connections and massive data transfer. For this purpose, several emerging technologies are implemented, resulting in virtualization and self-organization of most of their components, which raises important challenges related to safety. In order to contribute to their resolution, this paper proposes a novel architecture for incident management on 5G. The approach combines the conventional risk management schemes with the Endsley Situational Awareness model, thus improving effectiveness in different aspects, among them the ability to adapt to complex and dynamical monitoring environments, and countermeasure tracking or the role of context when decision-making. The proposal takes into account all layers for information processing in 5G mobile networks, ranging from infrastructure to the actuators responsible for deploying corrective measures

Seguridad en Redes de Nueva Generación- Arquitectura para la Gestión de Incidencias

New-generation networks aim to facilitate the deployment of ever faster networks and by which a greater amount of information flows. To comply with this objective, proposes the combination of different tecnologı́as Such is the case with self-organization and virtualization. of its components. This in turn raises important desafı́os in the field of security. In order to contribute to its improvement, the present artı́culo introduces an architecture for the management of incidents on mobile networks. The proposal combines the basis of conventional risk management schemes with the Situational Consciousness model proposed by Endsley. Different aspects have been taken into account, such as the ability to adapt to dynamic monitoring environments, the monitoring of countermeasures or the impact of the context of impact on the decision-making process. The covers all levels of information processing in networks from the network infrastructure to the deployment of mobile services. the actuators responsible for implementing countermeasures