Hacia nuevas estrategias terapéuticas basadas en cannabinoides para el síndrome de Dravet

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 17-12-2021Dravet syndrome (DS) is a rare genetic epileptic encephalopathy affecting children which, in approximately 70-80% of patients, is caused by loss-of-function mutations in the Scn1a gene, which encodes the α1 subunit of the voltage-gated sodium channel (NaV1.1). Clinically, these patients present different types of epileptic seizures, which are frequently accompanied by some comorbidities such as developmental delay, cognitive impairment, hyperactivity, autistic traits and a rate of premature mortality of around 20%. Therapeutic strategies typically involve a complex polytherapy, with antiepileptic drugs whose action mechanisms are focused on correcting hyperexcitability, i.e., the imbalance between excitation and inhibition occurring in epilepsy. Current treatment algorithms often lead to tolerance issues as well as adverse effects, and around 30% of patients remain refractory. Therefore, there is an urgent need for new and effective therapeutic approaches...El síndrome de Dravet (SD) es una encefalopatía epiléptica rara y genética que afecta a niños y que, en alrededor del 70-80% de los pacientes, está causado por mutaciones con pérdida de función en el gen Scn1a, que codifica la subunidad α1 del canal de sodio dependiente de voltaje (NaV1.1). En cuanto a la clínica, estos pacientes presentan diversos tipos de crisis epilépticas, que a menudo se acompañan por algunas comorbilidades tales como retraso en el desarrollo, alteraciones cognitivas, hiperactividad, rasgos autistas y una tasa de muerte prematura de alrededor del 20%. Las estrategias terapéuticas normalmente implican una compleja politerapia, con fármacos antiepilépticos cuyos mecanismos de acción se centran en corregir la hiperexcitiblidad, es decir, el desequilibrio entre excitación e inhibición que ocurre en situaciones de epilepsia. Los algoritmos de tratamiento actuales a menudo conllevan problemas de tolerancia, así como efectos adversos, y alrededor del 30% de los pacientes permanecen refractarios. Por ello, es urgente la búsqueda de nuevas aproximaciones terapéuticas eficaces...Fac. de MedicinaTRUEunpu

Estudio sobre la satisfacción de los usuarios de una biblioteca hospitalaria

To know the opinion of the users of the Hospital Puerta de Hierro Library with regard to services offered. Development: Observational, cross-sectional study performed in 2002, with a 28 questions questionnaire: 5 closed queries, 3 open queries and 20 general questions, following Likert scale with a scoring from 1 (very poor) to 6 (very satisfactory). 106 questionnaires were collected. Professionalism and staff good manners are the more valued by the library users. The worst are the dimensions of the reading room scarce collection of journals and books on specialities and furniture. Physicians and other medical staff are the less satisfied professionals Conclusions: Library users have expressed a medium-high degree of satisfaction in regard to facilities while they expressed a low degree of satisfaction in regard to infrastructure, furniture and dimensions of the reading room. [ESCUDERO GÓMEZ, C. 2007. [Satisfaction of users in a University Hospital Library]. Revista General de información y documentació

Spanish electronic Book Market: distribution and sales platforms, business models and digital reading

[EN] In accordance with known international data publishing industry, the ebook’s phenomenon is becoming further strong and solid. In The United States (US), from where are setting trends in the electronic book market development, from January to August 2010 sales increased 193% over the same period last year. According to the Association of American Publishers (AAP) report, "Sales of books (not including academics) for the period January to August 2010 amounted to 2910 million dollars. The e-book sales reached 9.03% of the total, compared to 3.31% throughout 2009”. In addition, this report revealed a parallel decrease phenomenon in print-book sales. In Spain, with data from the Ministerio de Cultura and published in the Boletín del Observatorio del Libro y la Lectura in December 2010, the domestic electronic publishing reached 12,839 new e-book titles, meaning 97.8% of digital and other publishing media materials and 16.0% of whole book’s production in Spain (Ministerio de Cultura, 2010). Over the same period last year, the electronic publishing has increased 40.1%. With regard to the grow experienced, in the Foro Internacional para Contenidos Digitales (FICOD 2009) held in Madrid in November 2009 the experts predicted deep changes in business models relating to print-books and digital publishing.

Spatial Algorithms for Geometric Contact Detection in Multibody System Dynamics

This article belongs to the Topic Dynamical Systems: Theory and Applications.In the present work, different algorithms for contact detection in multibody systems based on smooth contact modelling approaches are presented. Beginning with the simplest ones, some difficult interactions are subsequently introduced. In addition, a brief overview on the different kinds of contact/impact modelling is provided and an underlining of the advantages and the drawbacks of each of them is determined. Finally, some practical examples of each interaction are presented and analyzed and an outline of the issues arisen during the design process and how they have been solved in order to obtain stable and accurate results is given. The main goal of this paper is to provide a resource for the early-stage researchers in the field that serves as an introduction to the modelling of simple contact/impact events in the context of multibody system dynamics.The authors would like to acknowledge the Spanish Government through the MCYT Project "RETOS2015: sistema de monitorización integral de conjuntos mecánicos críticos para la mejora del mantenimiento en el transporte-maqstatus". The authors would also like to acknowledge the financial support received by the Community of Madrid through its multi-year agreement with University Carlos III focused on its policy "Excelencia para el Profesorado Universitario"

Dynamic Modeling of the Dissipative Contact and Friction Forces of a Passive Biped-Walking Robot

This article belongs to the Special Issue Optimization of Motion Planning and Control for Automatic Machines, Robots and Multibody Systems.This work presents and discusses a general approach for the dynamic modeling and analysis of a passive biped walking robot, with a particular focus on the feet-ground contact interaction. The main purpose of this investigation is to address the supporting foot slippage and viscoelastic dissipative contact forces of the biped robot-walking model and to develop its dynamics equations for simple and double support phases. For this investigation, special attention has been given to the detection of the contact/impact between the legs of the biped and the ground. The results have been obtained with multibody system dynamics applying forward dynamics. This study aims at examining and comparing several force models dealing with different approaches in the context of multibody system dynamics. The normal contact forces developed during the dynamic walking of the robot are evaluated using several models: Hertz, Kelvin-Voight, Hunt and Crossley, Lankarani and Nikravesh, and Flores. Thanks to this comparison, it was shown that the normal force that works best for this model is the dissipative Nonlinear Flores Contact Force Model (hysteresis damping parameter - energy dissipation). Likewise, the friction contact/impact problem is solved using the Bengisu equations. The numerical results reveal that the stable periodic solutions are robust. Integrators and resolution methods are also purchased, in order to obtain the most efficient ones for this model.This work was financially supported by the Spanish Government through the MCYT project "RETOS2015: sistema de monitorización integral de conjuntos mecánicos críticos para la mejora del mantenimiento en el transporte-maqstatus

Calculation of intercepted photosynthetically active radiation (IPAR) for traditional crops in Castilla y León, Spain

Trabajo presentado a la XII National and y III International Conference on Engineering Thermodynamics. Madrid, 2022Agriculture is one of the most important economic activities in the Castilla y León region (Spain), approximately one-third of the land area is destined for this use. The role of agriculture in rural areas is essential from a territorial perspective, where rural depopulation is originating a crisis in the countryside. Moreover, climate change is having a major impact on agricultural productivity as a consequence, among others, of the increase in the frequency and the severity of extreme events, especially in Mediterranean regions [1]. For these reasons, it is essential to highlight the vision of agriculture as a multifunctional activity. Besides good management, productivity depends on many other factors, such as soil properties or climatic factors. A decisive climatic variable, which is often not considered in the planning and management of the crops, is the Photosynthetically Active Radiation (PAR), specifically, the Intercepted Photosynthetically Active Radiation (IPAR). The main purpose of this study is to calculate and represent an estimation of IPAR values for the most characteristic crops of Castilla y León.The authors gratefully acknowledge the financial support provided by the Spanish Ministry of Science & Innovation under the I+D+i state program Challenges Research Projects (Ref. RTI2018-098900- B-I00). Elena Garrachón-Gómez thanks financial support provided by Junta de Castilla y León (Programa Operativo de Empleo Juvenil, Fondo Social Europeo e Iniciativa de Empleo Juvenil)

Reductive Hydrogenation of Sulfido-Bridged Tantalum Alkyl Complexes: A Mechanistic Insight

Hydrogenolysis of a series of alkyl sulfido-bridged tantalum(IV) dinuclear complexes [Ta(?5-C5Me5)R(?-S)]2 [R = Me, nBu (1), Et, CH2SiMe3, C3H5, Ph, CH2Ph (2), p-MeC6H4CH2 (3)] has led quantitatively to the Ta(III) tetrametallic sulfide cluster [Ta(?5-C5Me5)(?3-S)]4 (4) along with the corresponding alkane. Mechanistic information for the formation of the unique low-valent tetrametallic compound 4 was gathered by hydrogenation of the phenyl-substituted precursor [Ta(?5-C5Me5)Ph(?- S)]2, which proceeds through a stepwise hydrogenation process, disclosing the formation of the intermediate tetranuclear hydride sulfide [Ta2(?5-C5Me5)2(H)Ph(?-S)(?3-S)]2 (5). Extending our studies toward tantalum alkyl precursors containing functional groups susceptible to hydrogenation, such as the allyl-and benzylsubstituted compounds [Ta(?5-C5Me5)(?3-C3H5)(?-S)]2 and [Ta(?5-C5Me5)(CH2Ph)(?-S)]2 (2), enables alternative reaction pathways en route to the formation of 4. In the former case, the dimetallic system undergoes selective hydrogenation of the unsaturated allyl moiety, forming the asymmetric complex [{Ta(?5-C5Me5)(?3-C3H5)}(?-S)2{Ta(?5-C5Me5)(C3H7)}] (6) with only one propyl fragment. Species 2, in addition to the hydrogenation of one benzyl fragment and concomitant toluene release, also undergoes partial hydrogenation and dearomatization of the phenyl ring on the vicinal benzyl unity to give a ?5-cyclohexadienyl complex [Ta2(?5-C5Me5)2(?-CH2C6H6)(?-S)2] (7). The mechanistic implications of the latter hydrogenation process are discussed by means of DFT calculationsComunidad de MadridUniversidad de AlcaláPrograma Estímulo a la Investigación de Jóvenes Investigadore

Modelling multiple-simultaneous impact problems with a nonlinear smooth approach: pool/billiard application

Smooth approaches are able to model reasonably well contact/impact events between two bodies, showing some peculiarities when dealing with certain geometries and arising certain issues with the detection of the initial instant of contact. The characterization of multiple-simultaneous interaction systems, considering (or not) energy dissipation phenomena (mainly friction), is always an interesting research topic, addressed from different perspectives. In the present work, the process of design, optimization and verification of a multiple-impact, day-to-day multibody novel model is shown. Specifically, we have decided to focus on a pool/billiard game due to its geometry simplicity. The model involves several balls moving freely and rolling, suffering different kinds of contacts/impacts among them and against the cushions and the cloth. In this system, the proper modelling of both contact and friction forces in the multiple, simultaneous contacts and impacts events is critical to obtain consistent results. In addition, these forces are complicated to model because of its nonlinear behaviour. The different existing approaches when dealing with multiple-contact events are briefly described, along with their most distinctive features. Then, the interactions identified on the model are implemented using several nonlinear contact-force models, following a smooth-based approach and considering friction phenomena, aiming at determining the most suitable set of both contact and friction force models for each of these implemented interactions, which take place simultaneously, thus resulting in a complex system with multiple impacts. Subsequently, the solving method that provides the most accurate results at the minimum computational cost is determined by testing a simple shot. Finally, the different interactions on the model are verified using experimental results and previous works. One of the main goals of this work is to show the some of the issues that arise when dealing with multiple-simultaneous impact multibody systems from a smooth-contact approach, and how researchers can deal with them.The authors would like to thank the Spanish Government through the MCYT Project "RETOS2015: sistema de monitorización integral de conjuntos mecánicos críticos para la mejora del mantenimiento en el transportemaqstatus". The authors would also like to acknowledge the support received by the Community of Madrid through its multiyear agreement with University Carlos III focused on its policy "Excelencia para el Profesorado Universitario". Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

New support roller profile design for railway wheel re-profiling process by under-floor lathes with a single cutting tool

The wheel re-profiling is an important part of railway wheelset maintenance. Researchers and railway operators have been very concerned about how to minimize the loss of time during wheel re-profiling without decreasing safety. Avoiding wheelset disassembly means considerable time savings, while reducing wheel damage during operation. Underfloor wheel lathes are the most appropriate tool to achieve this double objective, and therefore the most used nowadays. Multi-cut tool lathes have the disadvantage of being extremely expensive. On the other hand, with single tool lathes, re-profiling is not smooth or safe enough when current convex profile support rollers are used. It is well known by the companies that during reprofiling the wheel suffers impacts/damaged. In this article, a methodology to optimize the profile of the support rollers used in underfloor single tool lathes for railway wheel re-profiling is proposed. This novel profile design will minimize damage and increase the safety of such lathes, since it proposes a greater smoothness in the process. Simulations of re-profiling process have been carried out by the finite element method showing that the designed roller profile reduces drastically the impact/damage during the operation. The impact generated between the re-profiling wheel and the rollers is avoided. Profile-optimized support rollers have been used in a real underfloor wheel lathe, showing good results.This work was financially supported by the Spanish Government through the MCYT project 395 “RETOS2015: sistema de monitorización integral de conjuntos mecánicos críticos para la mejora del mantenimiento en el transporte-maqstatus.