Noninvasive imaging of 5-HT3 receptor trafficking in live cells: from biosynthesis to endocytosis.

Sequential stages in the life cycle of the ionotropic 5-HT(3) receptor (5-HT(3)R) were resolved temporally and spatially in live cells by multicolor fluorescence confocal microscopy. The insertion of the enhanced cyan fluorescent protein into the large intracellular loop delivered a fluorescent 5-HT(3)R fully functional in terms of ligand binding specificity and channel activity, which allowed for the first time a complete real-time visualization and documentation of intracellular biogenesis, membrane targeting, and ligand-mediated internalization of a receptor belonging to the ligand-gated ion channel superfamily. Fluorescence signals of newly expressed receptors were detectable in the endoplasmic reticulum about 3 h after transfection onset. At this stage receptor subunits assembled to form active ligand binding sites as demonstrated in situ by binding of a fluorescent 5-HT(3)R-specific antagonist. After novel protein synthesis was chemically blocked, the 5-HT(3) R populations in the endoplasmic reticulum and Golgi cisternae moved virtually quantitatively to the cell surface, indicating efficient receptor folding and assembly. Intracellular 5-HT(3) receptors were trafficking in vesicle-like structures along microtubules to the cell surface at a velocity generally below 1 mum/s and were inserted into the plasma membrane in a characteristic cluster distribution overlapping with actin-rich domains. Internalization of cell surface 5-HT(3) receptors was observed within minutes after exposure to an extracellular agonist. Our orchestrated use of spectrally distinguishable fluorescent labels for the receptor, its cognate ligand, and specific organelle markers can be regarded as a general approach allowing subcellular insights into dynamic processes of membrane receptor trafficking.

Research in psychopathology: epistemologic issues.

Etiologic research in psychiatry relies on an objectivist epistemology positing that human cognition is specified by the "reality" of the outer world, which consists of a totality of mind-independent objects. Truth is considered as some sort of correspondence relation between words and external objects, and mind as a mirror of nature. In our view, this epistemology considerably impedes etiologic research. Objectivist epistemology has been recently confronting a growing critique from diverse scientific fields. Alternative models in neurosciences (neuronal selection), artificial intelligence (connectionism), and developmental psychology (developmental biodynamics) converge in viewing living organisms as self-organizing systems. In this perspective, the organism is not specified by the outer world, but enacts its environment by selecting relevant domains of significance that constitute its world. The distinction between mind and body or organism and environment is a matter of observational perspective. These models from empirical sciences are compatible with fundamental tenets of philosophical phenomenology and hermeneutics. They imply consequences for research in psychopathology: symptoms cannot be viewed as disconnected manifestations of discrete localized brain dysfunctions. Psychopathology should therefore focus on how the person's self-coherence is maintained and on the understanding and empirical investigation of the systemic laws that govern neurodevelopment and the organization of human cognition.

Gestión de objetos digitales con ContentDm: estudio de caso en el Consorci de Biblioteques Universitàries de Catalunya y el Institut Cartogràfic de Catalunya

La gestión de objetos digitales, ya sean imágenes u otros tipos de ficheros digitales, supone un reto para las organizaciones. Es un proceso estratégico en el que están implicadas varias tareas dentro de la propia institución, desde una posible digitalización del documento físico a una correcta gestión documental pasando por la óptima definición de los requisitos funcionales que debe tener la herramienta que publique y gestione los objetos digitales. Se presenta el caso de dos instituciones, Consorci de Biblioteques Universitàries de Catalunya e Institut Cartogràfic de Catalunya, que afrontaron este proceso estratégico y escogieron ContentDm para la publicación y gestión de sus imágenes digitales.

The efficacy of single-trial multisensory memories.

This review article summarizes evidence that multisensory experiences at one point in time have long-lasting effects on subsequent unisensory visual and auditory object recognition. The efficacy of single-trial exposure to task-irrelevant multisensory events is its ability to modulate memory performance and brain activity to unisensory components of these events presented later in time. Object recognition (either visual or auditory) is enhanced if the initial multisensory experience had been semantically congruent and can be impaired if this multisensory pairing was either semantically incongruent or entailed meaningless information in the task-irrelevant modality, when compared to objects encountered exclusively in a unisensory context. Processes active during encoding cannot straightforwardly explain these effects; performance on all initial presentations was indistinguishable despite leading to opposing effects with stimulus repetitions. Brain responses to unisensory stimulus repetitions differ during early processing stages (-100 ms post-stimulus onset) according to whether or not they had been initially paired in a multisensory context. Plus, the network exhibiting differential responses varies according to whether or not memory performance is enhanced or impaired. The collective findings we review indicate that multisensory associations formed via single-trial learning exert influences on later unisensory processing to promote distinct object representations that manifest as differentiable brain networks whose activity is correlated with memory performance. These influences occur incidentally, despite many intervening stimuli, and are distinguishable from the encoding/learning processes during the formation of the multisensory associations. The consequences of multisensory interactions that persist over time to impact memory retrieval and object discrimination.

Visual representation of food in the brain : effects of repeated exposure and gut hormone secretion

The thesis at hand is concerned with the spatio-temporal brain mechanisms of visual food perception as investigated by electrical neuroimaging. Due to the increasing prevalence of obesity and its associated challenges for public health care, there is a need to better understand behavioral and brain processes underlying food perception and food-based decision-making. The first study (Study A) of this thesis was concerned with the role of repeated exposure to visual food cues. In our everyday lives we constantly and repeatedly encounter food and these exposures influence our food choices and preferences. In Study A, we therefore applied electrical neuroimaging analyses of visual evoked potentials to investigate the spatio-temporal brain dynamics linked to the repeated viewing of high- and low-energy food cues (published manuscript: "The role of energetic value in dynamic brain response adaptation during repeated food image viewing" (Lietti et al., 2012)). In this study, we found that repetitions differentially affect behavioral and brain mechanisms when high-energy, as opposed to low-energy foods and non-food control objects, were viewed. The representation of high-energy food remained invariant between initial and repeated exposures indicating that the sight of high-energy dense food induces less behavioral and neural adaptation than the sight of low-energy food and non-food control objects. We discuss this finding in the context of the higher salience (due to greater motivation and higher reward or hedonic valuation) of energy- dense food that likely generates a more mnemonically stable representation. In turn, this more invariant representation of energy-dense food is supposed to (partially) explain why these foods are over-consumed despite of detrimental health consequences. In Study Β we investigated food responsiveness in patients who had undergone Roux-en-Y gastric bypass surgery to overcome excessive obesity. This type of gastric bypass surgery is not only known to alter food appreciation, but also the secretion patterns of adipokines and gut peptides. Study Β aimed at a comprehensive and interdisciplinary investigation of differences along the gut-brain axis in bypass-operated patients as opposed to weight-matched non-operated controls. On the one hand, the spatio-temporal brain dynamics to the visual perception of high- vs. low-energy foods under differing states of motivation towards food intake (i.e. pre- and post-prandial) were assessed and compared between groups. On the other hand, peripheral gut hormone measures were taken in pre- and post-prandial nutrition state and compared between groups. In order to evaluate alterations in the responsiveness along the gut-brain-axis related to gastric bypass surgery, correlations between both measures were compared between both participant groups. The results revealed that Roux-en- Y gastric bypass surgery alters the spatio-temporal brain dynamics to the perception of high- and low-energy food cues, as well as the responsiveness along the gut-brain-axis. The potential role of these response alterations is discussed in relation to previously observed changes in physiological factors and food intake behavior post-Roux-en-Y gastric bypass surgery. By doing so, we highlight potential behavioral, neural and endocrine (i.e. gut hormone) targets for the future development of intervention strategies for deviant eating behavior and obesity. Together, the studies showed that the visual representation of foods in the brain is plastic and that modulations in neural activity are already noted at early stages of visual processing. Different factors of influence such as a repeated exposure, Roux-en-Y gastric bypass surgery, motivation (nutrition state), as well as the energy density of the visually perceived food were identified. En raison de la prévalence croissante de l'obésité et du défi que cela représente en matière de santé publique, une meilleure compréhension des processus comportementaux et cérébraux liés à la nourriture sont nécessaires. En particulier, cette thèse se concentre sur l'investigation des mécanismes cérébraux spatio-temporels liés à la perception visuelle de la nourriture. Nous sommes quotidiennement et répétitivement exposés à des images de nourriture. Ces expositions répétées influencent nos choix, ainsi que nos préférences alimentaires. La première étude (Study A) de cette thèse investigue donc l'impact de ces exposition répétée à des stimuli visuels de nourriture. En particulier, nous avons comparé la dynamique spatio-temporelle de l'activité cérébrale induite par une exposition répétée à des images de nourriture de haute densité et de basse densité énergétique. (Manuscrit publié: "The role of energetic value in dynamic brain response adaptation during repeated food image viewing" (Lietti et al., 2012)). Dans cette étude, nous avons pu constater qu'une exposition répétée à des images représentant de la nourriture de haute densité énergétique, par opposition à de la nourriture de basse densité énergétique, affecte les mécanismes comportementaux et cérébraux de manière différente. En particulier, la représentation neurale des images de nourriture de haute densité énergétique est similaire lors de l'exposition initiale que lors de l'exposition répétée. Ceci indique que la perception d'images de nourriture de haute densité énergétique induit des adaptations comportementales et neurales de moindre ampleur par rapport à la perception d'images de nourriture de basse densité énergétique ou à la perception d'une « catégorie contrôle » d'objets qui ne sont pas de la nourriture. Notre discussion est orientée sur les notions prépondérantes de récompense et de motivation qui sont associées à la nourriture de haute densité énergétique. Nous suggérons que la nourriture de haute densité énergétique génère une représentation mémorielle plus stable et que ce mécanisme pourrait (partiellement) être sous-jacent au fait que la nourriture de haute densité énergétique soit préférentiellement consommée. Dans la deuxième étude (Study Β) menée au cours de cette thèse, nous nous sommes intéressés aux mécanismes de perception de la nourriture chez des patients ayant subi un bypass gastrique Roux- en-Y, afin de réussir à perdre du poids et améliorer leur santé. Ce type de chirurgie est connu pour altérer la perception de la nourriture et le comportement alimentaire, mais également la sécrétion d'adipokines et de peptides gastriques. Dans une approche interdisciplinaire et globale, cette deuxième étude investigue donc les différences entre les patients opérés et des individus « contrôles » de poids similaire au niveau des interactions entre leur activité cérébrale et les mesures de leurs hormones gastriques. D'un côté, nous avons investigué la dynamique spatio-temporelle cérébrale de la perception visuelle de nourriture de haute et de basse densité énergétique dans deux états physiologiques différent (pre- et post-prandial). Et de l'autre, nous avons également investigué les mesures physiologiques des hormones gastriques. Ensuite, afin d'évaluer les altérations liées à l'intervention chirurgicale au niveau des interactions entre la réponse cérébrale et la sécrétion d'hormone, des corrélations entre ces deux mesures ont été comparées entre les deux groupes. Les résultats révèlent que l'intervention chirurgicale du bypass gastrique Roux-en-Y altère la dynamique spatio-temporelle de la perception visuelle de la nourriture de haute et de basse densité énergétique, ainsi que les interactions entre cette dernière et les mesures périphériques des hormones gastriques. Nous discutons le rôle potentiel de ces altérations en relation avec les modulations des facteurs physiologiques et les changements du comportement alimentaire préalablement déjà démontrés. De cette manière, nous identifions des cibles potentielles pour le développement de stratégies d'intervention future, au niveau comportemental, cérébral et endocrinien (hormones gastriques) en ce qui concerne les déviances du comportement alimentaire, dont l'obésité. Nos deux études réunies démontrent que la représentation visuelle de la nourriture dans le cerveau est plastique et que des modulations de l'activité neurale apparaissent déjà à un stade très précoce des mécanismes de perception visuelle. Différents facteurs d'influence comme une exposition repetee, le bypass gastrique Roux-en-Y, la motivation (état nutritionnel), ainsi que la densité énergétique de la nourriture qui est perçue ont pu être identifiés.

Cuadro de mando : control de ventas

La empresa Eatout quiere crear un Cuadro de Mando desde el que llevar el control de ventas de los restaurantes. Actualmente se comprueba qué locales faltan por cerrar la jornada de ventas y se lleva un registro de los errores desde una hoja de cálculo. Con este proyecto se pretende agilizar y facilitar la gestión de ventas, y analizar las posibles causas de esas faltas. Para ello, se creará una aplicación en .NET desde la que gestionarán los cierres que falten por realizar en una jornada indicando cuál ha sido el motivo. Después se analizarán estos datos a través de la herramienta de Business Objects de SAP creando un Cuadro de Mando.

Intel·ligència artificial aplicada a un joc beat'em up en 2D

Creació d'un joc del tipus Arcade beat'em up en 2D utilitzant escenaris amb una certa profunditat de moviment i dotant als personatges no jugadors i altres objectes d'Intel·ligència Artificial de manera que el seu comportament no sigui sempre lineal i aprofitant-ho per afegir nivells de dificultat.

Assistent per la preparació de distribucions

Projecte realitzat en el marc d'un conveni entre l’empresa Unit4 i la UAB. Unit4 es dedica a oferir solucions ERP per la gestió global de les empreses i serveis associats. El concepte de distribució dins de l’empresa es tradueix al paquet d’objectes (taules, formularis, classes, etc...), que s’entreguen al client i que solen contenir o bé versions inicials o bé algunes actualitzacions de versions ja existents. Aquest sistema és utilitzat per tots els sectors de l’empresa i la seva realització actual és completament manual. El projecte es centrarà en realitzar un conjunt d’eines per facilitar les diferents tasques implicades en la generació de distribucions.

A methodology to event reconstruction from trace images

The widespread use of digital imaging devices for surveillance (CCTV) and entertainment (e.g., mobile phones, compact cameras) has increased the number of images recorded and opportunities to consider the images as traces or documentation of criminal activity. The forensic science literature focuses almost exclusively on technical issues and evidence assessment [1]. Earlier steps in the investigation phase have been neglected and must be considered. This article is the first comprehensive description of a methodology to event reconstruction using images. This formal methodology was conceptualised from practical experiences and applied to different contexts and case studies to test and refine it. Based on this practical analysis, we propose a systematic approach that includes a preliminary analysis followed by four main steps. These steps form a sequence for which the results from each step rely on the previous step. However, the methodology is not linear, but it is a cyclic, iterative progression for obtaining knowledge about an event. The preliminary analysis is a pre-evaluation phase, wherein potential relevance of images is assessed. In the first step, images are detected and collected as pertinent trace material; the second step involves organising and assessing their quality and informative potential. The third step includes reconstruction using clues about space, time and actions. Finally, in the fourth step, the images are evaluated and selected as evidence. These steps are described and illustrated using practical examples. The paper outlines how images elicit information about persons, objects, space, time and actions throughout the investigation process to reconstruct an event step by step. We emphasise the hypothetico-deductive reasoning framework, which demonstrates the contribution of images to generating, refining or eliminating propositions or hypotheses. This methodology provides a sound basis for extending image use as evidence and, more generally, as clues in investigation and crime reconstruction processes.

Iterative reconstruction methods in two different MDCT scanners: Physical metrics and 4-alternative forced-choice detectability experiments - A phantom approach.

This paper characterizes and evaluates the potential of three commercial CT iterative reconstruction methods (ASIR?, VEO? and iDose(4 ()?())) for dose reduction and image quality improvement. We measured CT number accuracy, standard deviation (SD), noise power spectrum (NPS) and modulation transfer function (MTF) metrics on Catphan phantom images while five human observers performed four-alternative forced-choice (4AFC) experiments to assess the detectability of low- and high-contrast objects embedded in two pediatric phantoms. Results show that 40% and 100% ASIR as well as iDose(4) levels 3 and 6 do not affect CT number and strongly decrease image noise with relative SD constant in a large range of dose. However, while ASIR produces a shift of the NPS curve apex, less change is observed with iDose(4) with respect to FBP methods. With second-generation iterative reconstruction VEO, physical metrics are even further improved: SD decreased to 70.4% at 0.5 mGy and spatial resolution improved to 37% (MTF(50%)). 4AFC experiments show that few improvements in detection task performance are obtained with ASIR and iDose(4), whereas VEO makes excellent detections possible even at an ultra-low-dose (0.3 mGy), leading to a potential dose reduction of a factor 3 to 7 (67%-86%). In spite of its longer reconstruction time and the fact that clinical studies are still required to complete these results, VEO clearly confirms the tremendous potential of iterative reconstructions for dose reduction in CT and appears to be an important tool for patient follow-up, especially for pediatric patients where cumulative lifetime dose still remains high.

The changing preference of T and B cells for partners as T-dependent antibody responses develop.

Recirculating virgin CD4+ T cells spend their life migrating between the T zones of secondary lymphoid tissues where they screen the surface of interdigitating dendritic cells. T-cell priming starts when processed peptides or superantigen associated with class II MHC molecules are recognised. Those primed T cells that remain within the lymphoid tissue move to the outer T zone, where they interact with B cells that have taken up and processed antigen. Cognate interaction between these cells initiates immunoglobulin (Ig) class switch-recombination and proliferation of both B and T cells; much of this growth occurs outside the T zones B cells migrate to follicles, where they form germinal centres, and to extrafollicular sites of B-cell growth, where they differentiate into mainly short-lived plasma cells. T cells do not move to the extrafollicular foci, but to the follicles; there they proliferate and are subsequently involved in the selection of B cells that have mutated their Ig variable-region genes. During primary antibody responses T-cell proliferation in follicles produces many times the peak number of T cells found in that site: a substantial proportion of the CD4+ memory T-cell pool may originate from growth in follicles.

Pràctiques i rituals funeraris a Tàrraco i el seu ager (segles II aC-III/IV dC)

L’objectiu d’aquest projecte ha estat identificar i analitzar els rituals funeraris a celebrats als suburbis de Tàrraco i el seu territorium. Per tal d’assolir-lo hem revisat col•leccions de museus, arxius i informes arqueològics arribant a documentar 721 enterraments. A través de la recerca, hem estudiat les peculiaritats i els elements d’aixovar que les tombes presenten amb el suport de les fonts escrites. Hem detectat pràctiques rituals com ara libacions, sacrificis i objectes relacionats amb ofrenes funeràries a l’exterior de les tombes. Hem documentat certa una uniformitat general i repetiva pel que fa a la selecció dels aixovars funerari. No obstant això, hi ha algunes diferències sobretot en aixovars que provenen de les tombes d’individus morts prematurament (individus no casats, infants). També s’ha constatat una diferència sexual entre dones i homes pel que fa als objectes d’aixovar. Hem utilitzat l’evidència arqueològica i literària per tal de trobar el significat d’aquests artefactes quotidians que canvien de significat quan entren en contacte amb els morts. En revisar la informació procedent d’excavacions hem identificat espais rituals específics dins de la necròpolis com jardins funeraris i ustrina. Aquest estudi ha explorat la manera com l’arqueologia ens permeten identificar les pràctiques rituals dins les àrees funeràries. L’estudi de materials arqueològics documentats als estrats de freqüentació de les necròpolis ens ha permès detectar l’evidència material de la ritualitat.

Text2Emotion: un gestor d'experiències SOA : extracció d'emocions per al suport a la gestió de relació amb clients

Customer Experience Management (CEM) se ha convertido en un factor clave para el éxito de las empresas. CEM gestiona todas las experiencias que un cliente tiene con un proveedor de servicios o productos. Es muy importante saber como se siente un cliente en cada contacto y entonces poder sugerir automáticamente la próxima tarea a realizar, simplificando tareas realizadas por personas. En este proyecto se desarrolla una solución para evaluar experiencias. Primero se crean servicios web que clasifican experiencias en estados emocionales dependiendo del nivel de satisfacción, interés, … Esto es realizado a través de minería de textos. Se procesa y clasifica información no estructurada (documentos de texto) que representan o describen las experiencias. Se utilizan métodos de aprendizaje supervisado. Esta parte es desarrollada con una arquitectura orientada a servicios (SOA) para asegurar el uso de estándares y que los servicios sean accesibles por cualquier aplicación. Estos servicios son desplegados en un servidor de aplicaciones. En la segunda parte se desarrolla dos aplicaciones basadas en casos reales. En esta fase Cloud computing es clave. Se utiliza una plataforma de desarrollo en línea para crear toda la aplicación incluyendo tablas, objetos, lógica de negocio e interfaces de usuario. Finalmente los servicios de clasificación son integrados a la plataforma asegurando que las experiencias son evaluadas y que las tareas de seguimiento son automáticamente creadas.