Knockdown of Kiaa0319 Reduces Dendritic Spine Density

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to exhibit differential spatial-temporal expression patterns in the brain throughout development, which suggests that the polycystic kidney disease (PKD) domain encoded by KIAA0319 facilitates cell-cell adhesion to enable neuronal precursors to crawl up the radial glia during neuronal migration. With the knowledge of KIAA0319 involvement in early neurogenesis, we were interested in determining how different KIAA0319 expression may impact cortical neurons in layer II and III during early adulthood. We show that KIAA0319 knockdown in cortical pyramidal neurons significantly reduces the dendritic spine density. Studies have shown that changes in dendritic spine morphology and density affect properties of neural circuitry. Henceforth, this finding may reveal a link between the Kiaa0319 gene and the deficit of the neural processing task of reading due to reduced spines density. Finding a correlation between Kiaa0319 expression and its influence on dendritic spine development may lead to a greater insight of a direct link between the dyslexia susceptibility gene and the biological mechanism that causes dyslexia.

Neocortical hyperexcitability defect in a mutant mouse model of spike-wave epilepsy, {\it stargazer}

Single-locus mutations in mice can express epileptic phenotypes and provide critical insights into the naturally occurring defects that alter excitability and mediate synchronization in the central nervous system (CNS). One such recessive mutation (on chromosome (Chr) 15), stargazer(stg/stg) expresses frequent bilateral 6-7 cycles per second (c/sec) spike-wave seizures associated with behavioral arrest, and provides a valuable opportunity to examine the inherited lesion associated with spike-wave synchronization.^ The existence of distinct and heterogeneous defects mediating spike-wave discharge (SWD) generation has been demonstrated by the presence of multiple genetic loci expressing generalized spike-wave activity and the differential effects of pharmacological agents on SWDs in different spike-wave epilepsy models. Attempts at understanding the different basic mechanisms underlying spike-wave synchronization have focused on $\gamma$-aminobutyric acid (GABA) receptor-, low threshold T-type Ca$\sp{2+}$ channel-, and N-methyl-D-aspartate receptor (NMDA-R)-mediated transmission. It is believed that defects in these modes of transmission can mediate the conversion of normal oscillations in a trisynaptic circuit, which includes the neocortex, reticular nucleus and thalamus, into spike-wave activity. However, the underlying lesions involved in spike-wave synchronization have not been clearly identified.^ The purpose of this research project was to locate and characterize a distinct neuronal hyperexcitability defect favoring spike-wave synchronization in the stargazer brain. One experimental approach for anatomically locating areas of synchronization and hyperexcitability involved an attempt to map patterns of hypersynchronous activity with antibodies to activity-induced proteins.^ A second approach to characterizing the neuronal defect involved examining the neuronal responses in the mutant following application of pharmacological agents with well known sites of action.^ In order to test the hypothesis that an NMDA receptor mediated hyperexcitability defect exists in stargazer neocortex, extracellular field recordings were used to examine the effects of CPP and MK-801 on coronal neocortical brain slices of stargazer and wild type perfused with 0 Mg$\sp{2+}$ artificial cerebral spinal fluid (aCSF).^ To study how NMDA receptor antagonists might promote increased excitability in stargazer neocortex, two basic hypotheses were tested: (1) NMDA receptor antagonists directly activate deep layer principal pyramidal cells in the neocortex of stargazer, presumably by opening NMDA receptor channels altered by the stg mutation; and (2) NMDA receptor antagonists disinhibit the neocortical network by blocking recurrent excitatory synaptic inputs onto inhibitory interneurons in the deep layers of stargazer neocortex.^ In order to test whether CPP might disinhibit the 0 Mg$\sp{2+}$ bursting network in the mutant by acting on inhibitory interneurons, the inhibitory inputs were pharmacologically removed by application of GABA receptor antagonists to the cortical network, and the effects of CPP under 0 Mg$\sp{2+}$aCSF perfusion in layer V of stg/stg were then compared with those found in +/+ neocortex using in vitro extracellular field recordings. (Abstract shortened by UMI.) ^

Mapping of mechanical properties of cement paste microstructures

The presented study is related to the EU 7 th Framework Programme CODICE (COmputationally Driven design of Innovative CEment-based materials). The main aim of the project is the development of a multi-scale model for the computer based simulation of mechanical and durability performance of cementitious materials. This paper reports results of micro/nano scale characterisation and mechanical property mapping of cementitious skeletons formed by the cement hydration at different ages. Using the statistical nanoindentation and micro-mechanical property mapping technique, intrinsic properties of different hydrate phases, and also the possible interaction (or overlapping) of different phases (e.g. calcium-silcate-hydrates) has been studied. Results of the mapping and statistical indentation testing appear to suggest the possible existence of more hydrate phases than the commonly reported LD and HD C-S-H and CH phases

Multiphase transformer-coupled converter: two different strategies for energy conversion

The operation of a multiphase topology, ideally, without energy storage presents the advantage of achieving very high efficiency over a wide load range as well as a fast dynamic response. However, ideal no-energy storage operation also implies a limitation in the regulation capability of the topology, the output voltage can only take discrete values. These features (high efficiency and discrete regulation capability) of the proposed energy conversion strategy enable the topology as a candidate for `DC-DC transformer' applications. The advantages, drawbacks and the operating principle of this concept, implemented with a `closed chain' magnetic structure have been already presented. In this work, the minimum energy storage operation, is applied to two different magnetic structures. These magnetic structures are called `closed chain' and `pyramidal' the main advantage of the `pyramidal' coupling structure is to improve the size of the converter without increasing the operating frequency. Both magnetic structures are analyzed, compared and experimentally implemented.

Bond modelling of prestressed concrete during the prestressing force release

This paper presents an analytical model for simulating the bond between steel and concrete, in precast prestressed concrete elements, during the prestressing force release. The model establishes a relationship between bond stress, steel and concrete stress and slip in such concrete structures. This relationship allows us to evaluate the bond stress in the transmission zone, where bond stress is not constant, along the whole prestressing force release process. The model is validated with the results of a series of tests, considering different steel indentation depths and concrete covers and is extended to evaluate the transmission length. This capability has been checked by comparing the transmission length predicted by the model and one measured experimentally in two series of tests.

Determination of the mechanical properties of amorphous materials through instrumented nanoindentation

A novel methodology based on instrumented indentation is developed to determine the mechanical properties of amorphous materials which present cohesive-frictional behaviour. The approach is based on the concept of a universal hardness equation, which results from the assumption of a characteristic indentation pressure proportional to the hardness. The actual universal hardness equation is obtained from a detailed finite element analysis of the process of sharp indentation for a very wide range of material properties, and the inverse problem (i.e. how to extract the elastic modulus, the compressive yield strength and the friction angle) from instrumented indentation is solved. The applicability and limitations of the novel approach are highlighted. Finally, the model is validated against experimental data in metallic and ceramic glasses as well as polymers, covering a wide range of amorphous materials in terms of elastic modulus, yield strength and friction angle.

Study of bond stress-slip relationship and radial dilation in prestressed concrete

This paper presents two test procedures for evaluating the bond stress–slip and the slip–radial dilation relationships when the prestressing force is transmitted by releasing the steel (wire or strand) in precast prestressed elements. The bond stress–slip relationship is obtained with short length specimens, to guarantee uniform bond stress, for three depths of the wire indentation (shallow, medium and deep). An analytical model for bond stress–slip relationship is proposed and compared with the experimental results. The model is also compared with the experimental results of other researchers. Since numerical models for studying bond-splitting problems in prestressed concrete require experimental data about dilatancy angle (radial dilation), a test procedure is proposed to evaluate these parameters. The obtained values of the radial dilation are compared with the prior estimated by numerical modelling and good agreement is reached

Selective area growth and characterization of InGaN nano-disks implemented in GaN nanocolumns with different top morphologies

This work reports on the morphology control of the selective area growth of GaN-based nanostructures on c-plane GaN templates. By decreasing the substrate temperature, the nanostructures morphology changes from pyramidal islands (no vertical m-planes), to GaN nanocolumns with top semipolar r-planes, and further to GaN nanocolumns with top polar c-planes. When growing InGaN nano-disks embedded into the GaN nanocolumns, the different morphologies mentioned lead to different optical properties, due to the semi-polar and polar nature of the r-planes and c-planes involved. These differences are assessed by photoluminescence measurements at low temperature and correlated to the specific nano-disk geometry.

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.

A novel methodology to determine the mechanical properties of amorphous materials through instrumented nanoindentation

A novel methodology based on instrumented indentation was developed to characterize the mechanical properties of amorphous materials. The approach is based on the concept of a universal postulate that assumes the existence of a characteristic indentation pressure proportional to the hardness. This hypothesis was numerically validated. This method overcomes the limitation of the conventional indentation models (pile-up effects and pressure sensitivity materials).

Three-Dimensional Analysis of Spiny Dendrites Using Straightening and Unrolling Transforms

Current understanding of the synaptic organization of the brain depends to a large extent on knowledge about the synaptic inputs to the neurons. Indeed, the dendritic surfaces of pyramidal cells (the most common neuron in the cerebral cortex) are covered by thin protrusions named dendritic spines. These represent the targets of most excitatory synapses in the cerebral cortex and therefore, dendritic spines prove critical in learning, memory and cognition. This paper presents a new method that facilitates the analysis of the 3D structure of spine insertions in dendrites, providing insight on spine distribution patterns. This method is based both on the implementation of straightening and unrolling transformations to move the analysis process to a planar, unfolded arrangement, and on the design of DISPINE, an interactive environment that supports the visual analysis of 3D patterns.

Cohesive-frictional modelling of bond and splitting action of prestressing wire

This work shows a numerical procedure for bond between indented wires and concrete, and the coupled splitting of the concrete. The bond model is an interface, non-associative, plasticity model. It is coupled with a cohesive fracture model for concrete to take into account the splitting of such concrete. The radial component of the prestressing force, increased by Poisson’s effect, may split the surrounding concrete, decreasing the wire confinement and diminishing the bonding. The combined action of the bond and the splitting is studied with the proposed model. The results of the numerical model are compared with the results of a series of tests, such as those which showed splitting induced by the bond between wire and concrete. Tests with different steel indentation depths were performed. The numerical procedure accurately reproduces the experimental records and improves knowledge of this complex process.

An analytical model for simulating the bond of prestressed concrete during the prestressed force release

A bond analytical model is proposed in this paper. The model is capable of reproducing the bond stress developed between the steel and concrete, in precast prestressed elements, during the entire process of prestressing force release. The bond stress developed in the transmission zone, where the bond stress is not constant, is also obtained. The steel and concrete stresses as well as the slip between both materials can be also estimated by means of the relation established in the model between these parameters and the bond stress. The model is validated with the results of a series of tests, considering different steel indentation depths and concrete covers and it is extended to evaluate the transmission length. This has been checked by comparing the transmission length predicted by the model and one measured experimentally in two series of tests.

Simulador WKM para gestión de conocimiento en una WSN

La gestión del conocimiento (KM) se basa en la captación, filtración, procesamiento y análisis de unos datos en bruto que con dicho refinamiento podrán llegar a convertirse en conocimiento o Sabiduría. Estas prácticas tendrán lugar en este PFC en una WSN (Wireless Sensor Network) compuesta de unos sofisticados dispositivos comúnmente conocidos como “motas” y cuya principal característica son sus bajas capacidades en cuanto a memoria, batería o autonomía. Ha sido objetivo primordial de este Proyecto de fin de Carrera aunar una WSN con la Gestión del Conocimiento así como demostrar que es posible llevar a cabo grandes procesamientos de información, con tan bajas capacidades, si se distribuyen correctamente los procesos. En primera instancia, se introducen conceptos básicos acerca de las WSN (Wireless Sensor Networks) así como de los elementos principales en dichas redes. Tras conocer el modelo de arquitectura de comunicaciones se procede a presentar la Gestión del Conocimiento de forma teórica y a continuación la interpretación que se ha hecho a partir de diversas referencias bibliográficas para llevar a cabo la implementación del proyecto. El siguiente paso es describir punto por punto todos los componentes del Simulador; librerías, funcionamiento y demás cuestiones sobre configuración y puesta a punto. Como escenario de aplicación se plantea una red de sensores inalámbricos básica cuya topología y ubicación es completamente configurable. Se lleva a cabo una configuración a nivel de red basada en el protocolo 6LowPAN pero con posibilidad de simplificarlo. Los datos se procesan de acuerdo a un modelo piramidal de Gestión de Conocimiento adaptable a las necesidades del usuario. Mediante la utilización de las diversas opciones que proporciona la interfaz gráfica implementada y los documentos de resultados que se van generando, se puede llevar a cabo un detallado estudio posterior de la simulación y comprobar si se cumplen las expectativas planteadas. Knowledge management (KM) is based on the collection, filtering, processing and analysis of some raw data which such refinement it can be turned into knowledge or wisdom. These practices will take place in a WSN (Wireless Sensor Network) consists of sophisticated devices commonly known as "dots" and whose main characteristics are its low capacity for memory, battery or autonomy. A primary objective of this Project will be to join a WSN with Knowledge Management and show that it is possible make largo information processing, with such low capacity if the processes are properly distributed. First, we introduce basic concepts about the WSN (Wireless Sensor Networks) and major elements of these networks. After meeting the communications architecture model, we proceed to show the Knowledge Management theory and then the interpretation of several bibliographic references to carry out the project implementation. The next step is discovering point by point all over the Simulator components; libraries, operation and the rest of points about configuration and tuning. As application scenario we propose a basic wireless sensor network whose topology and location is completely customizable. It will perform a network level configuration based in W6LowPAN Protocol. Data is processed according to a pyramidal pattern Knowledge Management adaptable to the user´s needs. The hardware elements will suffer more or less energy dependence depending on their role and activity in the network. Through the various options that provide the graphical interface has been implemented and results documents that are generated, can be carried out after a detailed study of the simulation and verify compliance with the expectations raised.

Corpus de tesis de ingeniería : paralelismo de las conclusiones entre inglés y español

El objetivo de este Proyecto Fin de Carrera es abordar el análisis del capítulo de conclusiones de tesis de ingeniería de telecomunicación a partir de un corpus comparable en inglés y español. A través del léxico podrán conocerse las expresiones típicas y la estructura de capítulo de conclusiones, tanto en inglés como en español. Para empezar este Proyecto, se ha compilado los corpus que se quieren comparar, en total se ha digitalizado tres corpus, uno con 24 conclusiones de tesis doctorales en español, otro con el mismo número de capítulos de conclusiones de tesis doctorales en inglés (PhD) y por último un corpus de conclusiones de tesis de fin de máster y de grado. El primer análisis que se ha realizado es el de la estructura de las conclusiones a partir de los títulos y subtítulos del capítulo. Se han comparado los títulos más utilizados y se han comentado las coincidencias y diferencias entre los corpus. La estructura vista a través de los subtítulos, se ha comparado con la propuesta por la autora Glasman-Deal (2011) en trabajos académicos de investigación, principalmente en artículos de investigación. La siguiente parte del Proyecto se ha centrado en el estudio del léxico, para ello nos hemos ayudado de la herramienta informática Wordsmith tools de la que se han explicado sus herramientas y funciones más útiles para este trabajo entre ellas el plot, que informa número de archivos en la que aparece cada palabra en el corpus. Las palabras con mayor plot son las más usadas por todos los doctorandos cuando escriben el capítulo de conclusiones .Se han elaborado unas pirámides donde se han colocado las palabras propias del género académico de las tesis por orden de uso. Las más usadas, con mayor plot, en la base y según se asciende aparecen las que tienen menor plot, con el fin de ver de una forma gráfica el peso que tiene cada palabra en el corpus. El siguiente paso del análisis del léxico ha tenido el objetivo de diferenciar los contextos de uso de las palabras incluidas en las pirámides. Se ha diferenciado entre los usos de las palabras dependiendo de su denotación académica o técnica. Esta comparación ha permitido comprobar que dentro del mismo corpus un sustantivo como contribuciones tiene connotación positiva o negativa dependiendo del contexto. Con los ejemplos aportados por los corpus se proporciona una base para el análisis lingüístico, centrado en los sustantivos, en este trabajo. Para finalizar el Proyecto, se ha implementado una base de datos con los resultados obtenidos del análisis de los sustantivos en la que se pueden ver las palabras que corresponden a cada nivel de la pirámide y ejemplos del uso de estas palabras. The aim of this Project is to analyze the concluding chapter of PhD thesis in the field of telecommunication engineering by means of a comparable corpus in English and Spanish. Through the lexis we will be able to capture useful expressions and the typical structure of the chapter in these specialized thesis, either in English and Spanish. To start with, three corpora have been compiled. The first one consists of 24 concluding chapters of PhD thesis in Spanish; the second, is made up of the same number of chapters of PhD thesis in the English language; and finally, 24 further chapters of Master and Degree thesis in English were digitalized and prepared for lexis analysis. Second, the study of the structure of the chapter of conclusions has been carried out. In this part the most common titles in the chapter of conclusions have been analysed and compared so as to find differences and similarities between the two languages compared. Moreover, the structure found through the subtitles in the conclusions of the thesis has been compared with the structure proposed by Glasman-Deal (2011) in her book Science Research Writing. Third, the study has been focused on the lexis of each corpus. These corpora have been treated with a lexis analyser called Wordsmith tools. The variables of frequency and plot have been applied to withdraw the most widely used nouns from the list of all the words found in any of the corpus. A pyramidal structure has been designed in order to show the academic or gender nouns - the ones usually found in the concluding chapter of thesis – nouns with a higher plot in the corpus. Two different types of context have been found for these nouns: technical and academic denotation. To show the difference in use of these nouns, arranged examples of contexts are given for each of the words studied. Finally, a database has been implemented to arrange the results of the lexis study. In this database the most significant examples of each noun are shown.