Differences in the conectivity between hippocampi in patients with drug resistant epilepsy of the temporal lobe a resting-state fMRI study

Treball Final de Màster Universitari en Investigació en Cervell i Conducta. Codi: SBM024. Curs: 2019/2020.Introduction: Drug-resistant temporal lobe epilepsy is used to be treated through surgical interventions which resect the epileptogenic focus which is usually found in the hippocampus and/or the amygdala. Sometime this intervention produces some episodic memory loss, for this reason the functionality of this structures must be assessed. The objective from the present research is to observe the connectivity between both hippocampi, their functionality and evaluate their implication before the surgical process. Methodology: The sample was formed by 24 patients, all of them with temporal lobe epilepsy who completed a fMRI resting-state procedure. The images obtained from the fMRI were analysed with the software SPM12. Results: We have found the existence of slight but significative differences between the connectivity of both hippocampi, with les connectivity in patients with lesions in the left hemisphere tan lesions in the right hemisphere, as well as intragroup differences. Conclusions: The differences in connectivity inside of each group, are due to the functionality of the hippocampus, since the disconnection of one hippocampus from the other could indicate a lack of functionality. The pattern of greater affection in patients lefthanded is coherent with the greater prevalence of lack in episodic memory in this group. Neuropsychological studies with memory tasks could be useful to establish the functional connectivity in resting-state as a valid index to predict the hippocampal functionality

Propuesta de Materiales para la unidad: “El Sistema Nervioso” en 1º de Bachillerato

Treball Final de Màster Universitari en Professor/a d'Educació Secundària Obligatòria i Batxillerat, Formació Professional i Ensenyaments d'Idiomes. Codi SAP139. Curs: 2017/2018El trabajo de Final de Máster que presentamos recoge una serie de materiales didácticos contextualizados en la asignatura de Biología y Geología de primero de Bachillerato, los cuales están encaminados a promocionar una evaluación a través de Moodle. Con este trabajo, perteneciente a la modalidad 6 “Materiales didácticos” queremos aportar materiales que sirvan a los docentes a la hora de configurar su curso, en torno a la unidad didáctica sobre el sistema nervioso (Real Decreto 1105/2014). Con tal fin, creamos un Aula Virtual desde cero en la que añadimos unos materiales diseñados específicamente para la misma. Además se trabajaron los recursos que contiene una plataforma de este calibre para generar las rúbricas de evaluación, talleres Y formularios, que se ofrecen como material para el profesorado de bachillerato

Nous fàrmacs : medicina personalitzada

El desenvolupament de metodologies que permeten la seqüenciació de genomes individuals d'una manera ràpida i amb costos acceptables fa pensar que en el futur serà possible parlar de medicina personalitzada, és a dir, la possibilitat d'administrar a un pacient específic el fàrmac apropiat per a la indicació apropiada amb la dosi adequada. Això hauria de permetre evitar la falta d'eficàcia i seguretat d'una bona part dels fàrmacs utilitzats actualment, que està lligada a la gran variació genètica en la població general en els llocs d'acció dels fàrmacs i als mecanismes que en determinen l'absorció, el metabolisme i l'excreció. La farmacogenètica i, més àmpliament, la farmacogenòmica, són les ciències en què es basa la medicina personalitzada. El canvi més important en el desenvolupament de nous fàrmacs en l'era postgenòmica està lligat a la necessitat de desenvolupament conjunt del binomi assaig diagnòstic i tractament dirigit. El compliment de les promeses de la farmacogenòmica té implicacions que van més enllà dels aspectes purament científics, ja que requereixen un canvi radical en la pràctica de la medicina amb implicacions ètiques, legals, reguladores i econòmiques. Aquest article revisa les diferències entre el desenvolupament tradicional de fàrmacs i els canvis introduïts per l'ús de la informació genòmica en el desenvolupament de noves terapèutiques.The development of methodologies allowing for the sequencing of individual genomes in a rapid manner and with acceptable costs allows us to think that in the future it will be possible to speak of personalized medicine, i.e., the possibility to treat a particular patient with the drug for the right indication at the right dose. This should help to avoid the lack of efficacy and safety of a good part of the drugs used currently that is linked to the great genetic variability in the general population with regard to the sites of actions of drugs as well as in the mechanisms determining their absorption, metabolism and excretion. Pharmacogenetics and more widely pharmacogenomics are the sciences in which personalized medicine is based. The most important change in the development of new medicines in the postgenomic era is linked to the necessity of developing, at the same time, both a diagnostic assay and a targeted treatment. The fulfilment of the promises of pharmacogenomics has implications far beyond the pure scientific aspects as it requires a radical change in the way medicine is currently practised with ethical, legal, regulatory and economic implications. This paper reviews the differences between the traditional drug development and the changes introduced by the use of genetic information in the development of new therapies

Improving scalability of large-scale distributed Spiking Neural Network simulations on High Performance Computing systems using novel architecture-aware streaming hypergraph partitioning

After theory and experimentation, modelling and simulation is regarded as the third pillar of science, helping scientists to further their understanding of a complex system. In recent years there has been a growing scientific focus on computational neuroscience as a means to understand the brain and its functions, with large international projects (Human Brain Project, Brain Activity Map, MindScope and \textit{China Brain Project}) aiming to further our knowledge of high level cognitive functions. They are a testament to the enormous interest, difficulty and importance of solving the mysteries of the brain. Spiking Neural Network (SNN) simulations are widely used in the domain to facilitate experimentation. Scaling SNN simulations to large networks usually results in more-than-linear increase in computational complexity. The computing resources required at the brain scale simulation far surpass the capabilities of personal computers today. If those demands are to be met, distributed computation models need to be adopted, since there is a slow down of improvements in individual processors speed due to physical limitations on heat dissipation. This is a significant change that requires careful management of the workload in many levels: partition of work, communication and workload balancing, efficient inter-process communication and efficient use of available memory. If large scale neuronal network models are to be run successfully, simulators must consider these, and offer a viable solution to the challenges they pose. Large scale SNN simulations evidence most of the issues of general HPC systems evident in large distributed computation. Commonly used distribution of workload algorithms (round robin, random and manual allocation) do not take into consideration connectivity locality, which is natural in biological networks, which can lead to increased communication requirements when distributing the simulation in multiple computing nodes. State-of-the-art SNN simulations use dense communication collectives to distribute spike data. The common method of point to point communication in distributed computation is through dense patterns. Sparse communication collectives have been suggested to incur in lower overheads when the application's pattern of communication is sparse. In this work we characterise the bottlenecks on communication-bound SNN simulations and identify communication balance and sparsity as the main contributors to scalability. We propose hypergraph partitioning to distribute neurons along computing nodes to minimise communication (increasing sparsity). A hypergraph is a generalisation of graphs, where a (hyper)edge can link 2 or more vertices at once. Coupled with a novel use of sparse-aware communication collective, computational efficiency increases by up to 40.8 percent points and simulation time reduces by up to 73\%, compared to the common round-robin allocation in neuronal simulators. HPC systems have, by design, highly hierarchical communication network links, with qualitative differences in communication speed and latency between computing nodes. This can create a mismatch between the distributed simulation communication patterns and the physical capabilities of the hardware. If large distributed simulations are to take full advantage of these systems, the communication properties of the HPC need to be taken into consideration when allocating workload to route frequent, heavy communication through fast network links. Strategies that consider the heterogeneous physical communication capabilities are called architecture-aware. After demonstrating that hypergraph partitioning leads to more efficient workload allocation in SNN simulations, this thesis proposes a novel sequential hypergraph partitioning algorithm that incorporates network bandwidth via profiling. This leads to a significant reduction in execution time (up to 14x speedup in synthetic benchmark simulations compared to architecture-agnostic partitioners). The motivating context of this work is large scale brain simulations, however in the era of social media, large graphs and hypergraphs are increasingly relevant in many other scientific applications. A common feature of such graphs is that they are too big for a single machine to cope, both in terms of performance and memory requirements. State-of-the-art multilevel partitioning has been shown to struggle to scale to large graphs in distributed memory, not just because they take a long time to process, but also because they require full knowledge of the graph (not possible in dynamic graphs) and to fit the graph entirely in memory (not possible for very large graphs). To address those limitations we propose a parallel implementation of our architecture-aware streaming hypergraph partitioning algorithm (HyperPRAW) to model distributed applications. Results demonstrate that HyperPRAW produces consistent speedup over previous streaming approaches that only consider hyperedge overlap (up to 5.2x speedup). Compared to multilevel global partitioner in dense hypergraphs (those with high average cardinality), HyperPRAW is able to produce workload allocations that result in speeding up runtime in a synthetic simulation benchmark (up to 4.3x). HyperPRAW has the potential to scale to very large hypergraphs as it only requires local information to make allocation decisions, with an order of magnitude less memory footprint than global partitioners. The combined contributions of this thesis lead to a novel, parallel, scalable, streaming hypergraph partitioning algorithm (HyperPRAW) that can be used to help scale large distributed simulations in HPC systems. HyperPRAW helps tackle three of the main scalability challenges: it produces highly balanced distributed computation and communication, minimising idle time between computing nodes; it reduces the communication overhead by placing frequently communicating simulation elements close to each other (where the communication cost is minimal); and it provides a solution with a reasonable memory footprint that allows tackling larger problems than state-of-the-art alternatives such as global multilevel partitioning

Péptidos derivados de lactoferrina bovina contra la hipertensión arterial: inhibición de los sistemas angiotensina y endotelina

En esta Tesis Doctoral se ha caracterizado el mecanismo de acción de hidrolizados y péptidos antihipertensivos derivados de la proteína láctea lactoferrina bovina (LF). En concreto, se ha determinado su efecto sobre los principales componentes del sistema renina-angiotensina (RAS) y del sistema endotelina. Para ello, se han utilizado diferentes aproximaciones experimentales que incluyen en primer lugar ensayos in vitro para determinar los efectos inhibitorios sobre la actividad de la enzima conversora de angiotensina (ECA) y sobre la enzima conversora de endotelina (ECE). En segundo lugar, se realizaron ensayos funcionales ex vivo para comprobar en arterias aisladas los efectos vasoactivos de los péptidos e hidrolizados tanto sobre la actividad ECA y ECE como sobre los receptores para la angiotensina II, AT1, y para la endotelina-1, ETA. Además, se han llevado a cabo ensayos in vivo en ratas espontáneamente hipertensas (SHRs) para estudiar los efectos sobre la presión arterial (PA) tras la administración oral aguda y crónica. En este último caso se han determinado los niveles circulantes de actividad renina y ECA, angiotensina II (ang-II) y aldosterona. Finalmente se ha evaluado el efecto de los hidrolizados en la presión arterial de ratas normotensas Wistar-Kyoto (WKY). Se generaron hidrolizados de LF (HLF) utilizando la enzima pancreática pepsina y la proteasa de origen microbiano proteinasa K. Se evaluó el efecto sobre los componentes clave del RAS y del sistema endotelina de estos dos hidrolizados, junto con un HLF obtenido previamente con pepsina (pHLF) cuyo efecto antihipertensivo agudo en SHRs ya había sido descrito. Para poder abordar la implicación del sistema endotelina, en primer lugar se desarrolló un método in vitro para comprobar el efecto inhibidor sobre ECE. Este método se complementó con otro ex vivo, utilizando arterias aisladas de conejo, que permitió comprobar, en términos de vasoactividad, los efectos de los péptidos tanto sobre la actividad ECE como sobre los receptores ETA. La combinación de esta metodología con los ensayos in vitro y ex vivo de inhibición de ECA sugieren que el pHLF podría ejercer su efecto antihipertensivo como inhibidor dual de vasopeptidasas. Esto se ha evidenciado por su capacidad de inhibir in vitro las actividades ECA y ECE, y se ha confirmado por su efecto inhibidor ex vivo sobre la vasoconstricción ECA-dependiente inducida por angiotensina I, así como sobre la vasoconstricción ECE-dependiente inducida por proendotelina (big ET-1). Además, se evidenció el efecto inhibidor de este hidrolizado y de dos de sus péptidos mayoritarios (LIWKL y RPYL) sobre la vasoconstricción ECA-independiente inducida por ang-II, bloqueando los receptores AT1. La inhibición in vivo de la ECA por parte del pHLF fue confirmada por la reducción de los niveles circulantes de actividad ECA, ang-II y aldosterona, así como el incremento compensatorio de actividad renina, tras la administración oral mantenida del hidrolizado en la dieta. Finalmente, el hidrolizado de LF obtenido con proteinasa K podría ejercer su efecto antihipertensivo como inhibidor de la vasopeptidasa ECE, como se ha evidenciado por su capacidad de inhibir in vitro la actividad ECE, y se ha confirmado por su efecto inhibidor ex vivo sobre la vasoconstricción ECE-dependiente inducida por big ET-1. Además, la caracterización de los péptidos mayoritarios de este hidrolizado ha permitido identificar las secuencias GILRPY y REPYFGY, con efecto inhibidor de ECE. En conclusión, se ha demostrado que la proteólisis enzimática de LF es un método eficaz para generar hidrolizados con efectos antihipertensivos tras su administración oral, cuyos mecanismos de acción van más allá de la inhibición de la ECA

Desarrollo de videojuegos sobre la plataforma Android

Este PFC está enfocado a la elaboración de tres videojuegos para dispositivos móviles con sistema operativo Android. Para ello se ha estudiado la arquitectura del sistema operativo Android, así como las herramientas necesarias para el desarrollo de aplicaciones para Android. Tras esto, se ha pasado a investigar y aprender el funcionamiento de una librería Open Source para el desarrollo de videojuegos (AndEngine). Y como conclusión y aplicación de lo aprendido, se han desarrollado tres videojuegos utilizando la librería elegida y el resto de herramientas necesarias.Musoles Tornador, S. (2014). Desarrollo de videojuegos sobre la plataforma Android. http://hdl.handle.net/10251/43331.Archivo delegad

Carta que sobre la vida y virtudes del P. Vicente Juan [Texto impreso]

El texto aparece fechado en : "Valencia y Julio 5 de 1747"Sign. : A-D4, E

Antihypertensive Mechanism of Lactoferrin-Derived Peptides: Angiotensin Receptor Blocking Effect

Texto del artículo, no incluye figuras ni tablas.Looking for antihypertensive mechanisms beyond ACE inhibition, we assessed whether lactoferrin (LF)-derived peptides can act as receptor blockers to inhibit vasoconstriction induced by angiotensin II or endothelin-1. The lactoferricin B (LfcinB)-derived peptide LfcinB20–25 (RRWQWR), the low molecular weight LF hydrolysate (LFH < 3 kDa), and two peptides identified in LFH < 3 kDa (LIWKL and RPYL) were tested in ex vivo assays of vasoactive responses. The peptide RPYL was tested in radioligand receptor binding assays. Both LFH < 3 kDa and individual peptides inhibited angiotensin II-induced vasoconstriction. RPYL showed the highest ex vivo inhibitory effect and also inhibited binding of [125I]-(Sar1,Ile8)-angiotensin II to AT1 receptors. By contrast, neither LFH < 3 kDa nor RPYL inhibited endothelin-1 and depolarization-induced vasoconstrictions. In conclusion, LF-derived peptides selectively inhibit angiotensin II-induced vasoconstriction by blocking angiotensin AT1 receptors. Therefore, inhibition of angiotensin II-induced vasocontriction is suggested as a mechanism contributing along with ACE inhibition to the antihypertensive effect of some LF-derived peptides.This work was supported by Grants AGL2010-21009 from Ministerio de Educación y Ciencia – FEDER, Consolider Ingenio 2010, Fun-C-Food, CSD2007-00063, and network RETICS INVICTUS – RD12/0014/0004 from Instituto de Salud Carlos III. R. Fernández-Musoles is the recipient of a fellowship from Ministerio de Educación y Ciencia (BES-2008-004472).Peer reviewe

Mapping cFos expression after cerebellar and medial prefrontal deactivations in rats trained to acquire cocaine-induced preference conditioning

6th Mediterranean Conference of Neuroscience (MNS Malta 2017

Discursos gratulatorios, que en las visitas publicas... practicadas por la... ciudad de Valencia, cerca de... Don Josef Climent ... i Fr. Don Rafael Lasala ... [Texto impreso]

Sign. : [sol]3, A-C4, D2Letra inicial decorada y friso tip. decorativo en p. 1Notas a pie de pág. y reclamo