The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.

The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated after FMRFa, and blocking phospho-CREB2 blocked LTD. In addition to changes in the expression of ap-uch, the synaptic vesicle-associated protein synapsin was downregulated in LTD in a proteasome-dependent manner. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions.

Juvenile onset central nervous system folate deficiency and rheumatoid arthritis.

Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.

Evidence for VirB4-mediated dislocation of membrane-integrated VirB2 pilin during biogenesis of the Agrobacterium VirB/VirD4 type IV secretion system.

Agrobacterium VirB2 pilin is required for assembly of the VirB/VirD4 type IV secretion system (T4SS). The propilin is processed by signal sequence cleavage and covalent linkage of the N and C termini, and the cyclized pilin integrates into the inner membrane (IM) as a pool for assembly of the secretion channel and T pilus. Here, by use of the substituted cysteine accessibility method (SCAM), we defined the VirB2 IM topology and then identified distinct contributions of the T4SS ATPase subunits to the pilin structural organization. Labeling patterns of Cys-substituted pilins exposed to the membrane-impermeative, thiol-reactive reagent 3-(N-maleimidopropionyl)biocytin (MPB) supported a topology model in which two hydrophobic stretches comprise transmembrane domains, an intervening hydrophilic loop (residues 90 to 94) is cytoplasmic, and the hydrophilic N and C termini joined at residues 48 and 121 form a periplasmic loop. Interestingly, the VirB4 ATPase, but not a Walker A nucleoside triphosphate (NTP) binding motif mutant, induced (i) MPB labeling of Cys94, a residue that in the absence of the ATPase is located in the cytoplasmic loop, and (ii) release of pilin from the IM upon osmotic shock. These findings, coupled with evidence for VirB2-VirB4 complex formation by coimmunoprecipitation, support a model in which VirB4 functions as a dislocation motor to extract pilins from the IM during T4SS biogenesis. The VirB11 ATPase functioned together with VirB4 to induce a structural change in the pilin that was detectable by MPB labeling, suggestive of a role for VirB11 as a modulator of VirB4 dislocase activity.

The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.

The neuropeptide Phe-Met-Arg-Phe-NH(2) (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated after FMRFa, and blocking phospho-CREB2 blocked LTD. In addition to changes in the expression of ap-uch, the synaptic vesicle-associated protein synapsin was downregulated in LTD in a proteasome-dependent manner. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions.

Sensory and conceptual representations in memory: Motor images which cannot be imaged

The paper argues for a distinction between sensory-and conceptual-information storage in the human information-processing system. Conceptual information is characterized as meaningful and symbolic, while sensory information may exist in modality-bound form. Furthermore, it is assumed that sensory information does not contribute to conscious remembering and can be used only in data-driven process reptitions, which can be accompanied by a kind of vague or intuitive feeling. Accordingly, pure top-down and willingly controlled processing, such as free recall, should not have any access to sensory data. Empirical results from different research areas and from two experiments conducted by the authors are presented in this article to support these theoretical distinctions. The experiments were designed to separate a sensory-motor and a conceptual component in memory for two-digit numbers and two-letter items, when parts of the numbers or items were imaged or drawn on a tablet. The results of free recall and recognition are discussed in a theoretical framework which distinguishes sensory and conceptual information in memory.

Subtyping schizophrenia: A comparison of positive/negative and system-specific approaches

BACKGROUND Schizophrenia is a heterogeneous disorder. Over the years, different approaches have been proposed to approach this heterogeneity by categorizing symptom patterns. The study aimed to compare positive/negative and system-specific approaches to subtyping. METHODS We used the Positive and Negative Syndrome Scale (PANSS) and Bern Psychopathology Scale (BPS), which consists of subscales for three domains (language, affect and motor behavior) that are hypothesized to be related to specific brain circuits, to assess cross-sectional psychopathological characteristics in a sample of 100 inpatients with schizophrenia spectrum disorders. We then categorized participants into positive/negative and system-specific subgroups to allow comparisons of the two approaches. RESULTS The analyses revealed correlations between the PANSS positive subscore and the BPS affective subscore (r=.446, p<.001) and between the PANSS negative subscore and the BPS motor behavior subscore (r=.227, p=.023). As regards the positive and negative subtype, more participants were classified as positive in the language-dominant subtype (30.3%) and affect-dominant subtype (30.3%), whereas more were classified as negative in the motor behavior-dominant subtype (44.4%). However, most patients met the criteria for the mixed subtype. CONCLUSIONS The results suggest that the positive/negative and system-specific approaches can be regarded as complementary. Future studies should examine both approaches in a longitudinal assessment of psychopathological symptoms and link them with qualitative-phenomenological approaches.

Central and peripheral defects in motor units of the diaphragm of spinal muscular atrophy mice.

Spinal muscular atrophy (SMA) is characterized by motoneuron loss and muscle weakness. However, the structural and functional deficits that lead to the impairment of the neuromuscular system remain poorly defined. By electron microscopy, we previously found that neuromuscular junctions (NMJs) and muscle fibres of the diaphragm are among the earliest affected structures in the severe mouse SMA model. Because of certain anatomical features, i.e. its thinness and its innervation from the cervical segments of the spinal cord, the diaphragm is particularly suitable to characterize both central and peripheral events. Here we show by immunohistochemistry that, at postnatal day 3, the cervical motoneurons of SMA mice receive less stimulatory synaptic inputs. Moreover, their mitochondria become less elongated which might represent an early stage of degeneration. The NMJs of the diaphragm of SMA mice show a loss of synaptic vesicles and active zones. Moreover, the partly innervated endplates lack S100 positive perisynaptic Schwann cells (PSCs). We also demonstrate the feasibility of comparing the proteomic composition between diaphragm regions enriched and poor in NMJs. By this approach we have identified two proteins that are significantly upregulated only in the NMJ-specific regions of SMA mice. These are apoptosis inducing factor 1 (AIFM1), a mitochondrial flavoprotein that initiates apoptosis in a caspase-independent pathway, and four and a half Lim domain protein 1 (FHL1), a regulator of skeletal muscle mass that has been implicated in several myopathies.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Motor-Fahrräder und Automobile in Arabien

A. D.

Sonnen-Motor [Illustration] : Vorder- und Seitenansicht

Scan von Monochrom-Mikroform

Environmental assessment of low speed policies for motor vehicle mobility in city centres

streets in local residential areas in large cities, real traffic tests for pollutant emissions and fuel consumption have been carried out in Madrid city centre. Emission concentration and car activity were simultaneously measured by a Portable Emissions Measurement System. Real life tests carried out at different times and on different days were performed with a turbo-diesel engine light vehicle equipped with an oxidizer catalyst and using different driving styles with a previously trained driver. The results show that by reducing the speed limit from 50 km h-1 to 30 km h-1, using a normal driving style, the time taken for a given trip does not increase, but fuel consumption and NOx, CO and PM emissions are clearly reduced. Therefore, the main conclusion of this work is that reducing the speed limit in some narrow streets in residential and commercial areas or in a city not only increases pedestrian safety, but also contributes to reducing the environmental impact of motor vehicles and reducing fuel consumption. In addition, there is also a reduction in the greenhouse gas emissions resulting from the combustion of the fuel.

Physical data acquisition and PWM signal generation using a microcontroller allowing control for DC motor rotation speed

El objetivo de este proyecto es diseñar un sistema capaz de controlar la velocidad de rotación de un motor DC en función del valor de temperatura obtenido de un sensor. Para ello se generará con un microcontrolador una señal PWM, cuyo ciclo de trabajo estará en función de la temperatura medida. En lo que respecta a la fase de diseño, hay dos partes claramente diferenciadas, relativas al hardware y al software. En cuanto al diseño del hardware puede hacerse a su vez una división en dos partes. En primer lugar, hubo que diseñar la circuitería necesaria para adaptar los niveles de tensión entregados por el sensor de temperatura a los niveles requeridos por ADC, requerido para digitalizar la información para su posterior procesamiento por parte del microcontrolador. Por tanto hubo que diseñar capaz de corregir el offset y la pendiente de la función tensión-temperatura del sensor, a fin de adaptarlo al rango de tensión requerido por el ADC. Por otro lado, hubo que diseñar el circuito encargado de controlar la velocidad de rotación del motor. Este circuito estará basado en un transistor MOSFET en conmutación, controlado mediante una señal PWM como se mencionó anteriormente. De esta manera, al variar el ciclo de trabajo de la señal PWM, variará de manera proporcional la tensión que cae en el motor, y por tanto su velocidad de rotación. En cuanto al diseño del software, se programó el microcontrolador para que generase una señal PWM en uno de sus pines en función del valor entregado por el ADC, a cuya entrada está conectada la tensión obtenida del circuito creado para adaptar la tensión generada por el sensor. Así mismo, se utiliza el microcontrolador para representar el valor de temperatura obtenido en una pantalla LCD. Para este proyecto se eligió una placa de desarrollo mbed, que incluye el microcontrolador integrado, debido a que facilita la tarea del prototipado. Posteriormente se procedió a la integración de ambas partes, y testeado del sistema para comprobar su correcto funcionamiento. Puesto que el resultado depende de la temperatura medida, fue necesario simular variaciones en ésta, para así comprobar los resultados obtenidos a distintas temperaturas. Para este propósito se empleó una bomba de aire caliente. Una vez comprobado el funcionamiento, como último paso se diseñó la placa de circuito impreso. Como conclusión, se consiguió desarrollar un sistema con un nivel de exactitud y precisión aceptable, en base a las limitaciones del sistema. SUMMARY: It is obvious that day by day people’s daily life depends more on technology and science. Tasks tend to be done automatically, making them simpler and as a result, user life is more comfortable. Every single task that can be controlled has an electronic system behind. In this project, a control system based on a microcontroller was designed for a fan, allowing it to go faster when temperature rises or slowing down as the environment gets colder. For this purpose, a microcontroller was programmed to generate a signal, to control the rotation speed of the fan depending on the data acquired from a temperature sensor. After testing the whole design developed in the laboratory, the next step taken was to build a prototype, which allows future improvements in the system that are discussed in the corresponding section of the thesis.

Sistema para cambiar la geometría de un motor

En este proyecto se desarrolla un sistema electrónico para variar la geometría de un motor de un monoplaza que participa en la competición Fórmula SAE. Fórmula SAE es una competición de diseño de monoplazas para estudiantes, organizado por “Society of Automotive Enginners” (SAE). Este concurso busca la innovación tecnológica de la automoción, así como que estudiantes participen en un trabajo real, en el cual el objetivo es obtener resultados competitivos cumpliendo con una serie de requisitos. La variación de la geometría de un motor en un vehículo permite mejorar el rendimiento del monoplaza consiguiendo elevar el par de potencia del motor. Cualquier mejora en del vehículo en un ámbito de competición puede resultar determinante en el desenlace de la misma. El objetivo del proyecto es realizar esta variación mediante el control de la longitud de los tubos de admisión de aire o “runners” del motor de combustión, empleando un motor lineal paso a paso. A partir de la información obtenida por sensores de revoluciones del motor de combustión y la posición del acelerador se debe controlar la distancia de dichos tubos. Integrando este sistema en el bus CAN del vehículo para que comparta la información medida al resto de módulos. Por todo esto se realiza un estudio aclarando los aspectos generales del objetivo del trabajo, para la comprensión del proyecto a realizar, las posibilidades de realización y adquisición de conocimientos para un mejor desarrollo. Se presenta una solución basada en el control del motor lineal paso a paso mediante el microcontrolador PIC32MX795F512-L. Dispositivo del fabricante Microchip con una arquitectura de 32 bits. Este dispone de un módulo CAN integrado y distintos periféricos que se emplean en la medición de los sensores y actuación sobre el motor paso a paso empleando el driver de Texas Instruments DRV8805. Entonces el trabajo se realiza en dos líneas, una parte software de programación del control del sistema, empleando el software de Microchip MPLABX IDE y otra parte hardware de diseño de una PCB y circuitos acondicionadores para la conexión del microcontrolador, con los sensores, driver, motor paso a paso y bus CAN. El software empleado para la realización de la PCB es Orcad9.2/Layout. Para la evaluación de las medidas obtenidas por los sensores y la comprobación del bus CAN se emplea el kit de desarrollo de Microchip, MCP2515 CAN Bus Monitor Demo Board, que permite ver la información en el bus CAN e introducir tramas al mismo. ABSTRACT. This project develops an electronic system to vary the geometry of a car engine which runs the Formula SAE competition. Formula SAE is a design car competition for students, organized by "Society of Automotive Engineers" (SAE). This competition seeks technological innovation in the automotive industry and brings in students to participate in a real job, in which the objective is to obtain competitive results in compliance with certain requirements. Varying engine’s geometry in a vehicle improves car’s performance raising engine output torque. Any improvement in the vehicle in a competition field can be decisive in the outcome of it. The goal of the project is the variation by controlling the length of the air intake pipe or "runners" in a combustion engine, using a linear motor step. For these, uses the information gathered by speed sensors from the combustion engine and by the throttle position to control the distance of these tubes. This system is integrated in the vehicle CAN bus to share the information with the other modules. For all this is made a study to clarify the general aspects of the project in order to understand the activities developed inside the project, the different options available and also, to acquire knowledge for a better development of the project. The solution is based on linear stepper motor control by the microcontroller PIC32MX795F512-L. Device from manufacturer Microchip with a 32-bit architecture. This module has an integrated CAN various peripherals that are used in measuring the performance of the sensors and drives the stepper motor using Texas Instruments DRV8805 driver. Then the work is done in two lines, first, control programming software system using software MPLABX Microchip IDE and, second, hardware design of a PCB and conditioning circuits for connecting the microcontroller, with sensors, driver stepper motor and CAN bus. The software used to carry out the PCB is Orcad9.2/Layout. For the evaluation of the measurements obtained by the sensors and CAN bus checking is used Microchip development kit, MCP2515 CAN Bus Monitor Demo Board, that allows you to see the information on the CAN bus and enter new frames in the bus.

Posibilidades del motor 3D de la Nintendo DS

La consola portátil Nintendo DS es una plataforma de desarrollo muy presente entre la comunidad de desarrolladores independientes, con una extensa y nutrida escena homebrew. Si bien las capacidades 2D de la consola están muy aprovechadas, dado que la mayor parte de los esfuerzos de los creadores amateur están enfocados en este aspecto, el motor 3D de ésta (el que se encarga de representar en pantalla modelos tridimensionales) no lo está de igual manera. Por lo tanto, en este proyecto se tiene en vista determinar las capacidades gráficas de la Nintendo DS. Para ello se ha realizado una biblioteca de funciones en C que permite aprovechar las posibilidades que ofrece la consola en el terreno 3D y que sirve como herramienta para la comunidad homebrew para crear aplicaciones 3D de forma sencilla, dado que se ha diseñado como un sistema modular y accesible. En cuanto al proceso de renderizado se han sacado varias conclusiones. En primer lugar se ha determinado la posibilidad de asignar varias componentes de color a un mismo vértice (color material reactivo a la iluminación, color por vértice directo y color de textura), tanto de forma independiente como simultáneamente, pudiéndose utilizar para aplicar diversos efectos al modelo, como iluminación pre-calculada o simulación de una textura mediante color por vértice, ahorrando en memoria de video. Por otro lado se ha implementado un sistema de renderizado multi-capa, que permite realizar varias pasadas de render, pudiendo, de esta forma, aplicar al modelo una segunda textura mezclada con la principal o realizar un efecto de reflexión esférica. Uno de los principales avances de esta herramienta con respecto a otras existentes se encuentra en el apartado de animación. El renderizador desarrollado permite por un lado animación por transformación, consistente en la animación de mallas o grupos de vértices del modelo mediante el movimiento de una articulación asociada que determina su posición y rotación en cada frame de animación. Por otro lado se ha implementado un sistema de animación por muestreo de vértices mediante el cual se determina la posición de éstos en cada instante de la animación, generando frame a frame las poses que componen el movimiento (siendo este último método necesario cuando no se puede animar una malla por transformación). Un mismo modelo puede contener diferentes esqueletos, animados independientemente entre sí, y cada uno de ellos tener definidas varias costumbres de animación que correspondan a movimientos contextuales diferentes (andar, correr, saltar, etc). Además, el sistema permite extraer cualquier articulación para asociar su transformación a un objeto estático externo y que éste siga el movimiento de la animación, pudiendo así, por ejemplo, equipar un objeto en la mano de un personaje. Finalmente se han implementado varios efectos útiles en la creación de escenas tridimensionales, como el billboarding (tanto esférico como cilíndrico), que restringe la rotación de un modelo para que éste siempre mire a cámara y así poder emular la apariencia de un objeto tridimensional mediante una imagen plana, ahorrando geometría, o emplearlo para realizar efectos de partículas. Por otra parte se ha implementado un sistema de animación de texturas por subimágenes que permite generar efectos de movimiento mediante imágenes, sin necesidad de transformar geometría. ABSTRACT. The Nintendo DS portable console has received great interest within the independent developers’ community, with a huge homebrew scene. The 2D capabilities of this console are well known and used since most efforts of the amateur creators has been focused on this point. However its 3D engine (which handles with the representation of three-dimensional models) is not equally used. Therefore, in this project the main objective is to assess the Nintendo DS graphic capabilities. For this purpose, a library of functions in C programming language has been coded. This library allows the programmer to take advantage of the possibilities that the 3D area brings. This way the library can be used by the homebrew community as a tool to create 3D applications in an easy way, since it has been designed as a modular and accessible system. Regarding the render process, some conclusions have been drawn. First, it is possible to assign several colour components to the same vertex (material colour, reactive to the illumination, colour per vertex and texture colour), independently and simultaneously. This feature can be useful to apply certain effects on the model, such as pre-calculated illumination or the simulation of a texture using colour per vertex, providing video memory saving. Moreover, a multi-layer render system has been implemented. This system allows the programmer to issue several render passes on the same model. This new feature brings the possibility to apply to the model a second texture blended with the main one or simulate a spherical reflection effect. One of the main advances of this tool over existing ones consists of its animation system. The developed renderer includes, on the one hand, transform animation, which consists on animating a mesh or groups of vertices of the model by the movement of an associated joint. This joint determines position and rotation of the mesh at each frame of the animation. On the other hand, this tool also implements an animation system by vertex sampling, where the position of vertices is determined at every instant of the animation, generating the poses that build up the movement (the latter method is mandatory when a mesh cannot be animated by transform). A model can contain multiple skeletons, animated independently, each of them being defined with several animation customs, corresponding to different contextual movements (walk, run, jump, etc). Besides, the system allows extraction of information from any joint in order to associate its transform to a static external object, which will follow the movement of the animation. This way, any object could be equipped, for example, on the hand of a character. Finally, some useful effects for the creation of three-dimensional scenes have been implemented. These effects include billboarding (both spherical and cylindrical), which constraints the rotation of a model so it always looks on the camera's direction. This feature can provide the ability to emulate the appearance of a three-dimensional model through a flat image (saving geometry). It can also be helpful in the implementation of particle effects. Moreover, a texture animation system using sub-images has also been implemented. This system allows the generation of movement by using images as textures, without having to transform geometry.

Estudio de la vibración en baja frecuencia de motor eléctrico

Se realizará un análisis en baja frecuencia del comportamiento de sistemas vibratorios excitados principalmente por un motor eléctrico. El sistema está formado por un motor eléctrico acoplado a un volante de inercia que produce una carga sobre citado motor diferente según las configuraciones adoptadas, todo ello montado sobre una base metálica de acero, soportada esta, mediante resortes de diferente características. El estudio contemplará la identificación de frecuencias de excitación, resonancias, pérdidas de inserción de los sistemas, transmisibilidad, problemas de alineamiento, desajustes, modos propios... para cada una de las diferentes situaciones en las que opera el sistema. ABSTRACT. In this Project will proceed to an behavior analysis of vibrating systems in low frequency mainly excited by an electric motor. The system is comprised of an electric motor coupled to inertial flywheel (o flywheel) which produces a different load upon said engine according to the configurations adopted. This system is mounted on a steel metal base which is supported by springs of different characteristics. This study will consider the excitation frequency identification, system resonances, insertion loss, transmissibility, shaft dealignment, eccentricities, mismatches, modal frequencies of the plate… for each of the situations in which the system operates.