Exploring the emotional brain: Neural correlates of homeostatic and sensory-evoked emotions and their interaction in emotional rivalry

Human emotions are essential for survival. They are vital for the satisfaction of basic needs, the regulation of personal life and successful integration into social structures. Depending on which aspect of an emotion is used in its definition, many different theories offer possible answers to the questions of what emotions are and how they can be distinguished. The systematic investigation of emotions in cognitive neuroscience is relatively new, and neuroimaging studies specifically focussing on the neural correlates of different categories of emotions are still lacking. Therefore, the current thesis aimed at investigating the behavioural and neurophysiological correlates of different human emotional levels and their interaction in healthy subjects. We differentiated between emotions according to their cerebral entry site and neural processing pathways: homeostatic emotions, which are elicited by metabolic changes and processed by the interoceptive system (such as thirst, hunger, and need for air), and sensory-evoked emotions, which are evoked by external inputs via the eyes, ears or nose, or their corresponding mental representations and processed in the brain as sensory perception (e.g. fear, disgust, or pride). Using functional magnetic resonance imaging (fMRI) and behavioural parameters, we examined both the specific neural underpinnings of a homeostatic emotion (thirst) and a sensory-evoked emotion (disgust), and their interaction in a situation of emotional rivalry when both emotions were perceived simultaneously. This thesis comprises three research articles reporting the results of this research. The first paper presents disgust-related brain imaging data in a thirsty and a satiated condition. We found that disgust mainly activated the anterior insular cortex. In the thirsty condition, however, we observed an interaction effect between disgust and thirst: when thirsty, the subjects rated the disgusting stimulus as less repulsive. On the neurobiological level, this reduction of subjective disgust was accompanied by significantly reduced neural activity in the insular cortex. These results provide new neurophysiological evidence for a hierarchical organization among homeostatic and sensory-evoked emotions, revealing that in a situation of emotional conflict, homeostatic emotions are prioritized over sensory-evoked emotions. In the second paper, findings on brain perfusion over four different thirst stages are reported, with a special focus on the parametric progression of thirst. Cerebral perfusion differences over all thirst stages were found in the posterior insular cortex. Taking this result together with the findings of the first paper, the insular cortex seems to be a key player in human emotional processing, since it comprises specific representations of homeostatic and sensory-evoked emotions and also represents the site of cortical interaction between the two levels of emotions. Finally, although this thesis focussed on the homeostatic modulation of disgust, we were also interested in whether dehydration modulates taste perception. The results of this behavioural experiment are described in the third paper, where we show that dehydration alters the perception of neutral taste stimuli.

Invited review: Growth-promoting effects of colostrum in calves based on interaction with intestinal cell surface receptors and receptor-like transporters

The postnatal development and maturation of the gastrointestinal (GI) tract of neonatal calves is crucial for their survival. Major morphological and functional changes in the calf's GI tract initiated by colostrum bioactive substances promote the establishment of intestinal digestion and absorption of food. It is generally accepted that colostrum intake provokes the maturation of organs and systems in young calves, illustrating the significance of the cow-to-calf connection at birth. These postnatal adaptive changes of the GI tissues in neonatal calves are especially induced by the action of bioactive substances such as insulin-like growth factors, hormones, or cholesterol carriers abundantly present in colostrum. These substances interact with specific cell-surface receptors or receptor-like transporters expressed in the GI wall of neonatal calves to elicit their biological effects. Therefore, the abundance and activity of cell surface receptors and receptor-like transporters binding colostral bioactive substances are a key aspect determining the effects of the cow-to-calf connection at birth. The present review compiles the information describing the effects of colostrum feeding on selected serum metabolic and endocrine traits in neonatal calves. In this context, the current paper discusses specifically the consequences of colostrum feeding on the GI expression and activity of cell-receptors and receptor-like transporters binding growth hormone, insulin-like growth factors, insulin, or cholesterol acceptors in neonatal calves.

Contributions to the contextualization of human-machine spoken interaction systems

The design and development of spoken interaction systems has been a thoroughly studied research scope for the last decades. The aim is to obtain systems with the ability to interact with human agents with a high degree of naturalness and efficiency, allowing them to carry out the actions they desire using speech, as it is the most natural means of communication between humans. To achieve that degree of naturalness, it is not enough to endow systems with the ability to accurately understand the user’s utterances and to properly react to them, even considering the information provided by the user in his or her previous interactions. The system has also to be aware of the evolution of the conditions under which the interaction takes place, in order to act the most coherent way as possible at each moment. Consequently, one of the most important features of the system is that it has to be context-aware. This context awareness of the system can be reflected in the modification of the behaviour of the system taking into account the current situation of the interaction. For instance, the system should decide which action it has to carry out, or the way to perform it, depending on the user that requests it, on the way that the user addresses the system, on the characteristics of the environment in which the interaction takes place, and so on. In other words, the system has to adapt its behaviour to these evolving elements of the interaction. Moreover that adaptation has to be carried out, if possible, in such a way that the user: i) does not perceive that the system has to make any additional effort, or to devote interaction time to perform tasks other than carrying out the requested actions, and ii) does not have to provide the system with any additional information to carry out the adaptation, which could imply a lesser efficiency of the interaction, since users should devote several interactions only to allow the system to become adapted. In the state-of-the-art spoken dialogue systems, researchers have proposed several disparate strategies to adapt the elements of the system to different conditions of the interaction (such as the acoustic characteristics of a specific user’s speech, the actions previously requested, and so on). Nevertheless, to our knowledge there is not any consensus on the procedures to carry out these adaptation. The approaches are to an extent unrelated from one another, in the sense that each one considers different pieces of information, and the treatment of that information is different taking into account the adaptation carried out. In this regard, the main contributions of this Thesis are the following ones: Definition of a contextualization framework. We propose a unified approach that can cover any strategy to adapt the behaviour of a dialogue system to the conditions of the interaction (i.e. the context). In our theoretical definition of the contextualization framework we consider the system’s context as all the sources of variability present at any time of the interaction, either those ones related to the environment in which the interaction takes place, or to the human agent that addresses the system at each moment. Our proposal relies on three aspects that any contextualization approach should fulfill: plasticity (i.e. the system has to be able to modify its behaviour in the most proactive way taking into account the conditions under which the interaction takes place), adaptivity (i.e. the system has also to be able to consider the most appropriate sources of information at each moment, both environmental and user- and dialogue-dependent, to effectively adapt to the conditions aforementioned), and transparency (i.e. the system has to carry out the contextualizaton-related tasks in such a way that the user neither perceives them nor has to do any effort in providing the system with any information that it needs to perform that contextualization). Additionally, we could include a generality aspect to our proposed framework: the main features of the framework should be easy to adopt in any dialogue system, regardless of the solution proposed to manage the dialogue. Once we define the theoretical basis of our contextualization framework, we propose two cases of study on its application in a spoken dialogue system. We focus on two aspects of the interaction: the contextualization of the speech recognition models, and the incorporation of user-specific information into the dialogue flow. One of the modules of a dialogue system that is more prone to be contextualized is the speech recognition system. This module makes use of several models to emit a recognition hypothesis from the user’s speech signal. Generally speaking, a recognition system considers two types of models: an acoustic one (that models each of the phonemes that the recognition system has to consider) and a linguistic one (that models the sequences of words that make sense for the system). In this work we contextualize the language model of the recognition system in such a way that it takes into account the information provided by the user in both his or her current utterance and in the previous ones. These utterances convey information useful to help the system in the recognition of the next utterance. The contextualization approach that we propose consists of a dynamic adaptation of the language model that is used by the recognition system. We carry out this adaptation by means of a linear interpolation between several models. Instead of training the best interpolation weights, we make them dependent on the conditions of the dialogue. In our approach, the system itself will obtain these weights as a function of the reliability of the different elements of information available, such as the semantic concepts extracted from the user’s utterance, the actions that he or she wants to carry out, the information provided in the previous interactions, and so on. One of the aspects more frequently addressed in Human-Computer Interaction research is the inclusion of user specific characteristics into the information structures managed by the system. The idea is to take into account the features that make each user different from the others in order to offer to each particular user different services (or the same service, but in a different way). We could consider this approach as a user-dependent contextualization of the system. In our work we propose the definition of a user model that contains all the information of each user that could be potentially useful to the system at a given moment of the interaction. In particular we will analyze the actions that each user carries out throughout his or her interaction. The objective is to determine which of these actions become the preferences of that user. We represent the specific information of each user as a feature vector. Each of the characteristics that the system will take into account has a confidence score associated. With these elements, we propose a probabilistic definition of a user preference, as the action whose likelihood of being addressed by the user is greater than the one for the rest of actions. To include the user dependent information into the dialogue flow, we modify the information structures on which the dialogue manager relies to retrieve information that could be needed to solve the actions addressed by the user. Usage preferences become another source of contextual information that will be considered by the system towards a more efficient interaction (since the new information source will help to decrease the need of the system to ask users for additional information, thus reducing the number of turns needed to carry out a specific action). To test the benefits of the contextualization framework that we propose, we carry out an evaluation of the two strategies aforementioned. We gather several performance metrics, both objective and subjective, that allow us to compare the improvements of a contextualized system against the baseline one. We will also gather the user’s opinions as regards their perceptions on the behaviour of the system, and its degree of adaptation to the specific features of each interaction. Resumen El diseño y el desarrollo de sistemas de interacción hablada ha sido objeto de profundo estudio durante las pasadas décadas. El propósito es la consecución de sistemas con la capacidad de interactuar con agentes humanos con un alto grado de eficiencia y naturalidad. De esta manera, los usuarios pueden desempeñar las tareas que deseen empleando la voz, que es el medio de comunicación más natural para los humanos. A fin de alcanzar el grado de naturalidad deseado, no basta con dotar a los sistemas de la abilidad de comprender las intervenciones de los usuarios y reaccionar a ellas de manera apropiada (teniendo en consideración, incluso, la información proporcionada en previas interacciones). Adicionalmente, el sistema ha de ser consciente de las condiciones bajo las cuales transcurre la interacción, así como de la evolución de las mismas, de tal manera que pueda actuar de la manera más coherente en cada instante de la interacción. En consecuencia, una de las características primordiales del sistema es que debe ser sensible al contexto. Esta capacidad del sistema de conocer y emplear el contexto de la interacción puede verse reflejada en la modificación de su comportamiento debida a las características actuales de la interacción. Por ejemplo, el sistema debería decidir cuál es la acción más apropiada, o la mejor manera de llevarla a término, dependiendo del usuario que la solicita, del modo en el que lo hace, etcétera. En otras palabras, el sistema ha de adaptar su comportamiento a tales elementos mutables (o dinámicos) de la interacción. Dos características adicionales son requeridas a dicha adaptación: i) el usuario no ha de percibir que el sistema dedica recursos (temporales o computacionales) a realizar tareas distintas a las que aquél le solicita, y ii) el usuario no ha de dedicar esfuerzo alguno a proporcionar al sistema información adicional para llevar a cabo la interacción. Esto último implicaría una menor eficiencia de la interacción, puesto que los usuarios deberían dedicar parte de la misma a proporcionar información al sistema para su adaptación, sin ningún beneficio inmediato. En los sistemas de diálogo hablado propuestos en la literatura, se han propuesto diferentes estrategias para llevar a cabo la adaptación de los elementos del sistema a las diferentes condiciones de la interacción (tales como las características acústicas del habla de un usuario particular, o a las acciones a las que se ha referido con anterioridad). Sin embargo, no existe una estrategia fija para proceder a dicha adaptación, sino que las mismas no suelen guardar una relación entre sí. En este sentido, cada una de ellas tiene en cuenta distintas fuentes de información, la cual es tratada de manera diferente en función de las características de la adaptación buscada. Teniendo en cuenta lo anterior, las contribuciones principales de esta Tesis son las siguientes: Definición de un marco de contextualización. Proponemos un criterio unificador que pueda cubrir cualquier estrategia de adaptación del comportamiento de un sistema de diálogo a las condiciones de la interacción (esto es, el contexto de la misma). En nuestra definición teórica del marco de contextualización consideramos el contexto del sistema como todas aquellas fuentes de variabilidad presentes en cualquier instante de la interacción, ya estén relacionadas con el entorno en el que tiene lugar la interacción, ya dependan del agente humano que se dirige al sistema en cada momento. Nuestra propuesta se basa en tres aspectos que cualquier estrategia de contextualización debería cumplir: plasticidad (es decir, el sistema ha de ser capaz de modificar su comportamiento de la manera más proactiva posible, teniendo en cuenta las condiciones en las que tiene lugar la interacción), adaptabilidad (esto es, el sistema ha de ser capaz de considerar la información oportuna en cada instante, ya dependa del entorno o del usuario, de tal manera que adecúe su comportamiento de manera eficaz a las condiciones mencionadas), y transparencia (que implica que el sistema ha de desarrollar las tareas relacionadas con la contextualización de tal manera que el usuario no perciba la manera en que dichas tareas se llevan a cabo, ni tampoco deba proporcionar al sistema con información adicional alguna). De manera adicional, incluiremos en el marco propuesto el aspecto de la generalidad: las características del marco de contextualización han de ser portables a cualquier sistema de diálogo, con independencia de la solución propuesta en los mismos para gestionar el diálogo. Una vez hemos definido las características de alto nivel de nuestro marco de contextualización, proponemos dos estrategias de aplicación del mismo a un sistema de diálogo hablado. Nos centraremos en dos aspectos de la interacción a adaptar: los modelos empleados en el reconocimiento de habla, y la incorporación de información específica de cada usuario en el flujo de diálogo. Uno de los módulos de un sistema de diálogo más susceptible de ser contextualizado es el sistema de reconocimiento de habla. Este módulo hace uso de varios modelos para generar una hipótesis de reconocimiento a partir de la señal de habla. En general, un sistema de reconocimiento emplea dos tipos de modelos: uno acústico (que modela cada uno de los fonemas considerados por el reconocedor) y uno lingüístico (que modela las secuencias de palabras que tienen sentido desde el punto de vista de la interacción). En este trabajo contextualizamos el modelo lingüístico del reconocedor de habla, de tal manera que tenga en cuenta la información proporcionada por el usuario, tanto en su intervención actual como en las previas. Estas intervenciones contienen información (semántica y/o discursiva) que puede contribuir a un mejor reconocimiento de las subsiguientes intervenciones del usuario. La estrategia de contextualización propuesta consiste en una adaptación dinámica del modelo de lenguaje empleado en el reconocedor de habla. Dicha adaptación se lleva a cabo mediante una interpolación lineal entre diferentes modelos. En lugar de entrenar los mejores pesos de interpolación, proponemos hacer los mismos dependientes de las condiciones actuales de cada diálogo. El propio sistema obtendrá estos pesos como función de la disponibilidad y relevancia de las diferentes fuentes de información disponibles, tales como los conceptos semánticos extraídos a partir de la intervención del usuario, o las acciones que el mismo desea ejecutar. Uno de los aspectos más comúnmente analizados en la investigación de la Interacción Persona-Máquina es la inclusión de las características específicas de cada usuario en las estructuras de información empleadas por el sistema. El objetivo es tener en cuenta los aspectos que diferencian a cada usuario, de tal manera que el sistema pueda ofrecer a cada uno de ellos el servicio más apropiado (o un mismo servicio, pero de la manera más adecuada a cada usuario). Podemos considerar esta estrategia como una contextualización dependiente del usuario. En este trabajo proponemos la definición de un modelo de usuario que contenga toda la información relativa a cada usuario, que pueda ser potencialmente utilizada por el sistema en un momento determinado de la interacción. En particular, analizaremos aquellas acciones que cada usuario decide ejecutar a lo largo de sus diálogos con el sistema. Nuestro objetivo es determinar cuáles de dichas acciones se convierten en las preferencias de cada usuario. La información de cada usuario quedará representada mediante un vector de características, cada una de las cuales tendrá asociado un valor de confianza. Con ambos elementos proponemos una definición probabilística de una preferencia de uso, como aquella acción cuya verosimilitud es mayor que la del resto de acciones solicitadas por el usuario. A fin de incluir la información dependiente de usuario en el flujo de diálogo, llevamos a cabo una modificación de las estructuras de información en las que se apoya el gestor de diálogo para recuperar información necesaria para resolver ciertos diálogos. En dicha modificación las preferencias de cada usuario pasarán a ser una fuente adicional de información contextual, que será tenida en cuenta por el sistema en aras de una interacción más eficiente (puesto que la nueva fuente de información contribuirá a reducir la necesidad del sistema de solicitar al usuario información adicional, dando lugar en consecuencia a una reducción del número de intervenciones necesarias para llevar a cabo una acción determinada). Para determinar los beneficios de las aplicaciones del marco de contextualización propuesto, llevamos a cabo una evaluación de un sistema de diálogo que incluye las estrategias mencionadas. Hemos recogido diversas métricas, tanto objetivas como subjetivas, que nos permiten determinar las mejoras aportadas por un sistema contextualizado en comparación con el sistema sin contextualizar. De igual manera, hemos recogido las opiniones de los participantes en la evaluación acerca de su percepción del comportamiento del sistema, y de su capacidad de adaptación a las condiciones concretas de cada interacción.

Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme plays a crucial role in repression

The yeast transcriptional repressor Tup1, tethered to DNA, represses to strikingly different degrees transcription elicited by members of two classes of activators. Repression in both cases is virtually eliminated by mutation of either member of the cyclin-kinase pair Srb10/11. In contrast, telomeric chromatin affects both classes of activators equally, and in neither case is that repression affected by mutation of Srb10/11. In vitro, Tup1 interacts with RNA polymerase II holoenzyme bearing Srb10 as well as with the separated Srb10. These and other findings indicate that at least one aspect of Tup1's action involves interaction with the RNA polymerase II holoenzyme.

Grenzüberschreitende Zusammenarbeit im Alpenraum: Wechselwirkung zwischen EUSALP und EVTZ? = Transnational cooperation in the Alpine region: interaction between EUSALP and EGTC? EDAP 2/2016

The Treaty of Lisbon (2009) explicitly added - in Article 3 of the Treaty on the European Union (TEU) and Article 174 of the Treaty on the Functioning of the European Union (TFEU) - the principle of territorial cohesion to the already existing principles of social and economic cohesion between the EU Member States. To concretely reach the objective of territorial cohesion, the EU created – on the one hand - the legal instrument of the “European Grouping for Territorial Cooperation” adopted through regulation n. 1082/2006 (EGTC). This allows cross-border cooperation between local and regional authorities. On the other hand, in 2009 a new form of European transnational cooperation has been introduced, the so called Macro Regional Strategy (MRS). This was firstly applied to the Baltic Sea Region in order to give to this cross - border geographical area a coordinated framework in specific policy fields, such as the environment and the infrastructures. Both concepts - EGTC and MRS - are based on the fundamental idea of supporting the territorial and cross - border cooperation between local, regional and national authorities and other stakeholders. Despite this common aspect, the two instruments differ profoundly in terms of form, structure and content. While the MRS is to be considered as a political integrated framework without its own financial resources, the instrument of the EGTC is based on a stable legal basis. To this extent, the alpine region - a large geographic area in the heart of Europe with a longstanding tradition in crossborder cooperation - represents an interesting practical example with regard to the implementation of these two forms of cooperation across borders. In fact, the countries and regions in the Alpine area are unified through the Alps and face, therefore, common challenges: that is why this “region” is ideally suited to be the ground for experiments regarding transnational tools and strategies.

Determinants of biological activity of nanomaterials in innate immunity cells: the role of aspect ratio, environmental contaminants and protein corona

As defined by the European Union, “ ’Nanomaterial’ (NM) means a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or agglomerate, where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm ” (2011/696/UE). Given their peculiar physico-chemical features, nanostructured materials are largely used in many industrial fields (e.g. cosmetics, electronics, agriculture, biomedical) and their applications have astonishingly increased in the last fifteen years. Nanostructured materials are endowed with very large specific surface area that, besides making them very useful in many industrial processes, renders them very reactive towards the biological systems and, hence, potentially endowed with significant hazard for human health. For these reasons, in recent years, many studies have been focused on the identification of toxic properties of nanostructured materials, investigating, in particular, the mechanisms behind their toxic effects as well as their determinants of toxicity. This thesis investigates two types of nanostructured TiO2 materials, TiO2 nanoparticles (NP), which are yearly produced in tonnage quantities, and TiO2 nanofibres (NF), a relatively novel nanomaterial. Moreover, several preparations of MultiWalled Carbon Nanotubes (MWCNT), another nanomaterial widely present in many products, are also investigated.- Although many in vitro and in vivo studies have characterized the toxic properties of these materials, the identification of their determinants of toxicity is still incomplete. The aim of this thesis is to identify the structural determinants of toxicity, using several in vitro models. Specific fields of investigation have been a) the role of shape and the aspect ratio in the determination of biological effects of TiO2 nanofibres of different length; b) the synergistic effect of LPS and TiO2 NP on the expression of inflammatory markers and the role played therein by TLR-4; c) the role of functionalization and agglomeration in the biological effects of MWCNT. As far as biological effects elicited by TiO2 NF are concerned, the first part of the thesis demonstrates that long TiO2 nanofibres caused frustrated phagocytosis, cytotoxicity, hemolysis, oxidative stress and epithelial barrier perturbation. All these effects were mitigated by fibre shortening through ball-milling. However, short TiO2 NF exhibited enhanced ability to activate acute pro-inflammatory effects in macrophages, an effect dependent on phagocytosis. Therefore, aspect ratio reduction mitigated toxic effects, while enhanced macrophage activation, likely rendering the NF more prone to phagocytosis. These results suggest that, under in vivo conditions, short NF will be associated with acute inflammatory reaction, but will undergo a relatively rapid clearance, while long NF, although associated with a relatively smaller acute activation of innate immunity cells, are not expected to be removed efficiently and, therefore, may be associated to chronic inflammatory responses. As far as the relationship between the effects of TiO2 NP and LPS, investigated in the second part of the thesis, are concerned, TiO2 NP markedly enhanced macrophage activation by LPS through a TLR-4-dependent intracellular pathway. The adsorption of LPS onto the surface of TiO2 NP led to the formation of a specific bio-corona, suggesting that, when bound to TiO2 NP, LPS exerts a much more powerful pro-inflammatory effect. These data suggest that the inflammatory changes observed upon exposure to TiO2 NP may be due, at least in part, to their capability to bind LPS and, possibly, other TLR agonists, thus enhancing their biological activities. Finally, the last part of the thesis demonstrates that surface functionalization of MWCNT with amino or carboxylic groups mitigates the toxic effects of MWCNT in terms of macrophage activation and capability to perturb epithelial barriers. Interestingly, surface chemistry (in particular surface charge) influenced the protein adsorption onto the MWCNT surface, allowing to the formation of different protein coronae and the tendency to form agglomerates of different size. In particular functionalization a) changed the amount and the type of proteins adsorbed to MWCNT and b) enhanced the tendency of MWCNT to form large agglomerates. These data suggest that the different biological behavior of functionalized and pristine MWCNT may be due, at least in part, to the different tendency to form large agglomerates, which is significantly influenced by their different capability to interact with proteins contained in biological fluids. All together, these data demonstrate that the interaction between physico-chemical properties of nanostructured materials and the environment (cells + biological fluids) in which these materials are present is of pivotal importance for the understanding of the biological effects of NM. In particular, bio-persistence and the capability to elicit an effective inflammatory response are attributable to the interaction between NM and macrophages. However, the interaction NM-cells is heavily influenced by the formation at the nano-bio interface of specific bio-coronae that confer a novel biological identity to the nanostructured materials, setting the basis for their specific biological activities.

The interaction between the implementation of an occupational health and safety management system and safety culture:a case study in the rubber industry

A prominent theme emerging in Occupational Health and Safety (OSH) is the development of management systems. A range of interventions, according to a prescribed route detailed by one of the management systems, can be introduced into an organisation with some expectation of improved OSH performance. This thesis attempts to identify the key influencing factors that may impact upon the process of introducing interventions, (according to B88800: 1996, Guide to Implementing Occupational Health and Safety Management Systems) into an organisation. To help identify these influencing factors a review of possible models from the sphere of Total Quality Management (TQM) was undertaken and the most suitable TQM model selected for development and use in aSH. By anchoring the aSH model's development in the reviewed literature a range ofeare, medium and low level influencing factors were identified. This model was developed in conjunction with the research data generated within the case study organisation (rubber manufacturer) and applied to the organisation. The key finding was that the implementation of an OSH intervention was dependant upon three broad vectors of influence. These are the Incentive to introduce change within an organisation which refers to the drivers or motivators for OSH. Secondly the Ability within the management team to actually implement the changes refers to aspects, amongst others, such as leadership, commitment and perceptions of OSH. Ability is in turn itself influenced by the environment within which change is being introduced. TItis aspect of Receptivity refers to the history of the plant and characteristics of the workforce. Aspects within Receptivity include workforce profile and organisational policies amongst others. It was found that the TQM model selected and developed for an OSH management system intervention did explain the core influencing factors and their impact upon OSH performance. It was found that within the organisation the results that may have been expected from implementation of BS8800:1996 were not realised. The OSH model highlighted that given the organisation's starting point, a poor appreciation of the human factors of OSH, gave little reward for implementation of an OSH management system. In addition it was found that general organisational culture can effectively suffocate any attempts to generate a proactive safety culture.

beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins.

One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways. Here we report the identification of Dishevelled 1 and Dishevelled 2 (Dvl1 and Dvl2) as beta-arrestin1 (betaarr1) interacting proteins. Dvl proteins participate as key intermediates in signal transmission from the seven membrane-spanning Frizzled receptors leading to inhibition of glycogen synthase kinase-3beta (GSK-3beta), stabilization of beta-catenin, and activation of the lymphoid enhancer factor (LEF) transcription factor. We find that phosphorylation of Dvl strongly enhances its interaction with betaarr1, suggesting that regulation of Dvl phosphorylation and subsequent interaction with betaarr1 may play a key role in the activation of the LEF transcription pathway. Because coexpression of the Dvl kinases, CK1epsilon and PAR-1, with Dvl synergistically activates LEF reporter gene activity, we reasoned that coexpression of betaarr1 with Dvl might also affect LEF-dependent gene activation. Interestingly, whereas betaarr1 or Dvl alone leads to low-level stimulation of LEF (2- to 5-fold), coexpression of betaarr1 with either Dvl1 or Dvl2 leads to a synergistic activation of LEF (up to 16-fold). Additional experiments with LiCl as an inhibitor of GSK-3beta kinase activity indicate that the step affected by betaarr1 is upstream of GSK-3beta and most likely at the level of Dvl. These results identify betaarr1 as a regulator of Dvl-dependent LEF transcription and suggest that betaarr1 might serve as an adapter molecule that can couple Frizzled receptors and perhaps other GPCRs to these important transcription pathways.

The role of vitamin D signalling in the interaction between mesenchymal mammary tumour cells and macrophages

The transition of epithelial-like tumour cells to those exhibiting mesenchymal characteristics (Epithelial-to-mesenchymal Transition; EMT) is an integral process in breast cancer metastasis. EMT can be promoted by Transforming growth factor-beta (TGF-β) which can be found at high levels in the tumour stroma. Tumour-associated macrophages (TAMs) can also induce EMT in breast cancer cells, which is one way that they promote breast cancer metastasis. Vitamin D signalling has been implicated in EMT suppression and plays a role in modulating macrophage differentiation and stimulating their anti-inflammatory functions. This project had two major aims. First, we aimed to create and verify a unique fluorescent reporter gene construct designed to evaluate the dynamics of EMT in real-time and at the single-cell level. While some components of this reporter system were successfully validated, work to complete the final reporter construct is ongoing. The second and main aspect of this project focused on exploring the ability of 1,25-dihydroxyvitamin D3 (1,25D3) to modulate the interaction between mesenchymal mammary tumour cells and TAMs. Unexpectedly, in short-term treatment (48 hours) studies of 4T1 murine mammary tumour cells, we observed that 1,25D3 and TGF-β signalling work together to increase expression of the mesenchymal markers, Snai1, Fn1, and Col1a1. 1,25D3 and TGF-β also synergistically activate transcription of the gene encoding the 1,25D3-catabolizing enzyme, Cyp24a1. The ability of 1,25D3 and TGF-β to enhance expression of these genes was diminished in a long-term treatment (14 days) of 4T1 cells, and this effect was accompanied by a decrease in cell proliferation. 1,25D3 may also cooperate with cytokines produced by normal macrophages and macrophages considered to be TAM-like. Conditioned media experiments revealed that in the presence of factors from normal macrophages, 1,25D3 enhanced expression of Fn1, and in the presence of factors from TAM-like macrophages, 1,25D3 enhanced expression of Fn1 and Cyp24a1. Rather than mitigating the interaction as hypothesized, 1,25D3 may exacerbate the tumour-promoting effects of the EMT-TAM relationship. Also, signalling pathways involved in the EMT-TAM relationship may synergize with 1,25D3 to upregulate Cyp24a1 expression. These findings are important for understanding the potential of vitamin D compounds to be used in the treatment of breast cancer.

Shock Train/Boundary-Layer Interaction in Rectangular Scramjet Isolators

Numerous studies of the dual-mode scramjet isolator, a critical component in preventing inlet unstart and/or vehicle loss by containing a collection of flow disturbances called a shock train, have been performed since the dual-mode propulsion cycle was introduced in the 1960s. Low momentum corner flow and other three-dimensional effects inherent to rectangular isolators have, however, been largely ignored in experimental studies of the boundary layer separation driven isolator shock train dynamics. Furthermore, the use of two dimensional diagnostic techniques in past works, be it single-perspective line-of-sight schlieren/shadowgraphy or single axis wall pressure measurements, have been unable to resolve the three-dimensional flow features inside the rectangular isolator. These flow characteristics need to be thoroughly understood if robust dual-mode scramjet designs are to be fielded. The work presented in this thesis is focused on experimentally analyzing shock train/boundary layer interactions from multiple perspectives in aspect ratio 1.0, 3.0, and 6.0 rectangular isolators with inflow Mach numbers ranging from 2.4 to 2.7. Secondary steady-state Computational Fluid Dynamics studies are performed to compare to the experimental results and to provide additional perspectives of the flow field. Specific issues that remain unresolved after decades of isolator shock train studies that are addressed in this work include the three-dimensional formation of the isolator shock train front, the spatial and temporal low momentum corner flow separation scales, the transient behavior of shock train/boundary layer interaction at specific coordinates along the isolator's lateral axis, and effects of the rectangular geometry on semi-empirical relations for shock train length prediction. A novel multiplane shadowgraph technique is developed to resolve the structure of the shock train along both the minor and major duct axis simultaneously. It is shown that the shock train front is of a hybrid oblique/normal nature. Initial low momentum corner flow separation spawns the formation of oblique shock planes which interact and proceed toward the center flow region, becoming more normal in the process. The hybrid structure becomes more two-dimensional as aspect ratio is increased but corner flow separation precedes center flow separation on the order of 1 duct height for all aspect ratios considered. Additional instantaneous oil flow surface visualization shows the symmetry of the three-dimensional shock train front around the lower wall centerline. Quantitative synthetic schlieren visualization shows the density gradient magnitude approximately double between the corner oblique and center flow normal structures. Fast response pressure measurements acquired near the corner region of the duct show preliminary separation in the outer regions preceding centerline separation on the order of 2 seconds. Non-intrusive Focusing Schlieren Deflectometry Velocimeter measurements reveal that both shock train oscillation frequency and velocity component decrease as measurements are taken away from centerline and towards the side-wall region, along with confirming the more two dimensional shock train front approximation for higher aspect ratios. An updated modification to Waltrup \& Billig's original semi-empirical shock train length relation for circular ducts based on centerline pressure measurements is introduced to account for rectangular isolator aspect ratio, upstream corner separation length scale, and major- and minor-axis boundary layer momentum thickness asymmetry. The latter is derived both experimentally and computationally and it is shown that the major-axis (side-wall) boundary layer has lower momentum thickness compared to the minor-axis (nozzle bounded) boundary layer, making it more separable. Furthermore, it is shown that the updated correlation drastically improves shock train length prediction capabilities in higher aspect ratio isolators. This thesis suggests that performance analysis of rectangular confined supersonic flow fields can no longer be based on observations and measurements obtained along a single axis alone. Knowledge gained by the work performed in this study will allow for the development of more robust shock train leading edge detection techniques and isolator designs which can greatly mitigate the risk of inlet unstart and/or vehicle loss in flight.

Vortex Shedding Dynamics in Long Aspect-Ratio Aerodynamics Bodies

The focus of the current dissertation is to study qualitatively the underlying physics of vortex-shedding and wake dynamics in long aspect-ratio aerodynamics in incompressible viscous flow through the use of the KLE method. We carried out a long series of numerical experiments in the cases of flow around the cylinder at low Reynolds numbers. The study of flow at low Reynolds numbers provides an insight in the fluid physics and also plays a critical role when applying to stalled turbine rotors. Many of the conclusions about the qualitative nature of the physical mechanisms characterizing vortex formation, shedding and further interaction analyzed here at low Re could be extended to other Re regimes and help to understand the separation of the boundary layers in airfoils and other aerodynamic surfaces. In the long run, it aims to provide a better understanding of the complex multi-physics problems involving fluid-structure-control interaction through improved mathematical computational models of the multi-physics process. Besides the scientific conclusions produced, the research work on streamlined and bluff-body condition will also serve as a valuable guide for the future design of blade aerodynamics and the placement of wind turbines and hydrakinetic turbines, increasing the efficiency in the use of expensive workforce, supplies, and infrastructure. After the introductory section describing the main fields of application of wind power and hydrokinetic turbines, we describe the main features and theoretical background of the numerical method used here. Then, we present the analysis of the numerical experimentation results for the oscillatory regime right before the onset of vortex shedding for circular cylinders. We verified the wake length of the closed near-wake behind the cylinder and analysed the decay of the wake at the wake formation region, and then studied the St-Re relationship at the Reynolds numbers before the wake sheds compared to the experimental data. We found a theoretical model that describes the time evolution of the amplitude of fluctuations in the vorticity field on the twin vortex wake, which accurately matches the numerical results in terms of the frequency of the oscillation and rate of decay. We also proposed a model based on an analog circuit that is able to interpret the concerning flow by reducing the number of degrees of freedom. It follows the idea of the non-linear oscillator and resembles the dynamics mechanism of the closed near-wake with a common configured sine wave oscillator. This low-dimensional circuital model may also help to understand the underlying physical mechanisms, related to vorticity transport, that give origin to those oscillations.

Baran: an interaction-centred user monitoring framework

User Quality of Experience (QoE) is a subjective entity and difficult to measure. One important aspect of it, User Experience (UX), corresponds to the sensory and emotional state of a user. For a user interacting through a User Interface (UI), precise information on how they are using the UI can contribute to understanding their UX, and thereby understanding their QoE. As well as a user’s use of the UI such as clicking, scrolling, touching, or selecting, other real-time digital information about the user such as from smart phone sensors (e.g. accelerometer, light level) and physiological sensors (e.g. heart rate, ECG, EEG) could contribute to understanding UX. Baran is a framework that is designed to capture, record, manage and analyse the User Digital Imprint (UDI) which, is the data structure containing all user context information. Baran simplifies the process of collecting experimental information in Human and Computer Interaction (HCI) studies, by recording comprehensive real-time data for any UI experiment, and making the data available as a standard UDI data structure. This paper presents an overview of the Baran framework, and provides an example of its use to record user interaction and perform some basic analysis of the interaction.

Machine learning techniques for implicit interaction using mobile sensors

Interactions in mobile devices normally happen in an explicit manner, which means that they are initiated by the users. Yet, users are typically unaware that they also interact implicitly with their devices. For instance, our hand pose changes naturally when we type text messages. Whilst the touchscreen captures finger touches, hand movements during this interaction however are unused. If this implicit hand movement is observed, it can be used as additional information to support or to enhance the users’ text entry experience. This thesis investigates how implicit sensing can be used to improve existing, standard interaction technique qualities. In particular, this thesis looks into enhancing front-of-device interaction through back-of-device and hand movement implicit sensing. We propose the investigation through machine learning techniques. We look into problems on how sensor data via implicit sensing can be used to predict a certain aspect of an interaction. For instance, one of the questions that this thesis attempts to answer is whether hand movement during a touch targeting task correlates with the touch position. This is a complex relationship to understand but can be best explained through machine learning. Using machine learning as a tool, such correlation can be measured, quantified, understood and used to make predictions on future touch position. Furthermore, this thesis also evaluates the predictive power of the sensor data. We show this through a number of studies. In Chapter 5 we show that probabilistic modelling of sensor inputs and recorded touch locations can be used to predict the general area of future touches on touchscreen. In Chapter 7, using SVM classifiers, we show that data from implicit sensing from general mobile interactions is user-specific. This can be used to identify users implicitly. In Chapter 6, we also show that touch interaction errors can be detected from sensor data. In our experiment, we show that there are sufficient distinguishable patterns between normal interaction signals and signals that are strongly correlated with interaction error. In all studies, we show that performance gain can be achieved by combining sensor inputs.

Safe and Collaborative Navigation & Interaction With Mobile Manipulators in Domestic Appliance Test Labs

Safe collaboration between a robot and human operator forms a critical requirement for deploying a robotic system into a manufacturing and testing environment. In this dissertation, the safety requirement for is developed and implemented for the navigation system of the mobile manipulators. A methodology for human-robot co-existence through a 3d scene analysis is also investigated. The proposed approach exploits the advance in computing capability by relying on graphic processing units (GPU’s) for volumetric predictive human-robot contact checking. Apart from guaranteeing safety of operators, human-robot collaboration is also fundamental when cooperative activities are required, as in appliance test automation floor. To achieve this, a generalized hierarchical task controller scheme for collision avoidance is developed. This allows the robotic arm to safely approach and inspect the interior of the appliance without collision during the testing procedure. The unpredictable presence of the operators also forms dynamic obstacle that changes very fast, thereby requiring a quick reaction from the robot side. In this aspect, a GPU-accelarated distance field is computed to speed up reaction time to avoid collision between human operator and the robot. An automated appliance testing also involves robotized laundry loading and unloading during life cycle testing. This task involves Laundry detection, grasp pose estimation and manipulation in a container, inside the drum and during recovery grasping. A wrinkle and blob detection algorithms for grasp pose estimation are developed and grasp poses are calculated along the wrinkle and blobs to efficiently perform grasping task. By ranking the estimated laundry grasp poses according to a predefined cost function, the robotic arm attempt to grasp poses that are more comfortable from the robot kinematic side as well as collision free on the appliance side. This is achieved through appliance detection and full-model registration and collision free trajectory execution using online collision avoidance.

Thermodynamic Study Of The Micellization Of Zwitterionic Surfactants And Their Interaction With Polymers In Water By Isothermal Titration Calorimetry.

The micellization of a homologous series of zwitterionic surfactants, a group of sulfobetaines, was studied using isothermal titration calorimetry (ITC) in the temperature range from 15 to 65 °C. The increase in both temperature and the alkyl chain length leads to more negative values of ΔGmic(0) , favoring the micellization. The entropic term (ΔSmic(0)) is predominant at lower temperatures, and above ca. 55-65 °C, the enthalpic term (ΔHmic(0)) becomes prevalent, figuring a jointly driven process as the temperature increases. The interaction of these sulfobetaines with different polymers was also studied by ITC. Among the polymers studied, only two induced the formation of micellar aggregates at lower surfactant concentration: poly(acrylic acid), PAA, probably due to the formation of hydrogen bonds between the carboxylic group of the polymer and the sulfonate group of the surfactant, and poly(sodium 4-styrenesulfonate), PSS, probably due to the incorporation of the hydrophobic styrene group into the micelles. The prevalence of the hydrophobic and not the electrostatic contributions to the interaction between sulfobetaine and PSS was confirmed by an increased interaction enthalpy in the presence of electrolytes (NaCl) and by the observation of a significant temperature dependence, the latter consistent with the proposed removal of hydrophobic groups from water.