Calcium oscillations

Changes in cellular calcium concentration control a wide range of physiological processes, from the subsecond release of synaptic neurotransmitters, to the regulation of gene expression over months or years. Calcium can also trigger cell death through both apoptosis and necrosis, and so the regulation of cellular calcium concentration must be tightly controlled through the concerted action of pumps, channels and buffers that transport calcium into and out of the cell cytoplasm. A hallmark of cellular calcium signalling is its spatiotemporal complexity: stimulation of cells by a hormone or neurotransmitter leads to oscillations in cytoplasmic calcium concentration that can vary markedly in time course, amplitude, frequency, and spatial range. In this chapter we review some of the biological roles of calcium, the experimental characterisation of complex dynamic changes in calcium concentration, and attempts to explain this complexity using computational models. We consider the "toolkit" of cellular proteins which influence calcium concentration, describe mechanistic models of key elements of the toolkit, and fit these into the framework of whole cell models of calcium oscillations and waves. Finally, we will touch on recent efforts to use stochastic modelling to elucidate elementary calcium signal events, and how these may evolve into global signals.

Effects of two teaching interventions on nursing students’ acquisition of competence in ECG interpretation

Purpose: Nurse ability to recognise patient arrhythmias could contribute to preventing in-hospital cardiac arrest. Research suggests that nurses and nursing students lack competence in electrocardiogram (ECG) interpretation. The aim of this study was to compare the effects of two training strategies on nursing students’ acquisition of competence in ECG interpretation. Materials and methods: A controlled randomised trial with 98 nursing students. Divided in groups of 12–16, participants were randomly allocated to one of the following 3-h teaching intervention groups: 1) traditional instructor-led (TILG), and 2) flipped classroom (FCG). Participants’ competence in ECG interpretation was measured in terms of knowledge (%), skills (%) and self-efficacy (%) using a specifically designed and previously validated toolkit at pre-test and post-test. Two-way MANOVA explored the interaction effect between ‘teaching group’ and ‘time of assessment’ and its impact on participants’ competence. Within-group differences at pre-test and post-test were explored by carrying out paired t-tests. Between-group differences at pre- and post-test were examined by performing independent t-test analysis. Results: There was a statistically significant interaction effect between ‘teaching group’ and ‘time of assessment’ on participants’ competence in ECG interpretation (F(3,190) = 86.541, p = 0.001; Wilks’ Λ = 0.423). At pre-test, differences in knowledge (TILG = 35.12 ± 12.07; FCG = 35.66 ± 10.66), skills (TILG = 14.05 ± 10.37; FCG = 14.82 ± 14.14), self-efficacy (TILG = 46.22 ± 23.78; FCG = 40.01 ± 21.77) and all other variables were non-significant (p > 0.05). At post-test, knowledge (TILG = 55.12 ± 14.16; FCG = 94.2 ± 7.31), skills (TILG = 36.90 ± 16.45; FCG = 86.43 ± 14.32) and self-efficacy (TILG = 70.78 ± 14.55; FCG = 79.98 ± 10.35) had significantly improved, regardless of the training received (p < 0.05). Nonetheless, participants in the FCG scored significantly higher than participants in the TILG in knowledge, skills and self-efficacy (p < 0.05). Conclusion: Flipping the classroom for teaching ECG interpretation to nursing students may be more effective than using a traditional instructor-led approach in terms of immediate acquisition of competence in terms of knowledge, skills and self-efficacy. Further research on the effects of both teaching strategies on the retention of the competence will be undertaken.

Collaborative Web-Based Simulation Platform for Construction Project Planning

Part 13: Virtual Reality and Simulation

Microfluidics-based single-cell functional proteomics microchip for portraying protein signal transduction networks within the framework of physicochemical principles, with applications in fundamental and translational cancer research

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing unique opportunities. This thesis describes an emerging microfluidics-based toolkit for single cell functional proteomics, focusing on the development of the single cell barcode chips (SCBCs) with applications in fundamental and translational cancer research.

The microchip designed to simultaneously quantify a panel of secreted, cytoplasmic and membrane proteins from single cells will be discussed at the beginning, which is the prototype for subsequent proteomic microchips with more sophisticated design in preclinical cancer research or clinical applications. The SCBCs are a highly versatile and information rich tool for single-cell functional proteomics. They are based upon isolating individual cells, or defined number of cells, within microchambers, each of which is equipped with a large antibody microarray (the barcode), with between a few hundred to ten thousand microchambers included within a single microchip. Functional proteomics assays at single-cell resolution yield unique pieces of information that significantly shape the way of thinking on cancer research. An in-depth discussion about analysis and interpretation of the unique information such as functional protein fluctuations and protein-protein correlative interactions will follow.

The SCBC is a powerful tool to resolve the functional heterogeneity of cancer cells. It has the capacity to extract a comprehensive picture of the signal transduction network from single tumor cells and thus provides insight into the effect of targeted therapies on protein signaling networks. We will demonstrate this point through applying the SCBCs to investigate three isogenic cell lines of glioblastoma multiforme (GBM).

The cancer cell population is highly heterogeneous with high-amplitude fluctuation at the single cell level, which in turn grants the robustness of the entire population. The concept that a stable population existing in the presence of random fluctuations is reminiscent of many physical systems that are successfully understood using statistical physics. Thus, tools derived from that field can probably be applied to using fluctuations to determine the nature of signaling networks. In the second part of the thesis, we will focus on such a case to use thermodynamics-motivated principles to understand cancer cell hypoxia, where single cell proteomics assays coupled with a quantitative version of Le Chatelier's principle derived from statistical mechanics yield detailed and surprising predictions, which were found to be correct in both cell line and primary tumor model.

The third part of the thesis demonstrates the application of this technology in the preclinical cancer research to study the GBM cancer cell resistance to molecular targeted therapy. Physical approaches to anticipate therapy resistance and to identify effective therapy combinations will be discussed in detail. Our approach is based upon elucidating the signaling coordination within the phosphoprotein signaling pathways that are hyperactivated in human GBMs, and interrogating how that coordination responds to the perturbation of targeted inhibitor. Strongly coupled protein-protein interactions constitute most signaling cascades. A physical analogy of such a system is the strongly coupled atom-atom interactions in a crystal lattice. Similar to decomposing the atomic interactions into a series of independent normal vibrational modes, a simplified picture of signaling network coordination can also be achieved by diagonalizing protein-protein correlation or covariance matrices to decompose the pairwise correlative interactions into a set of distinct linear combinations of signaling proteins (i.e. independent signaling modes). By doing so, two independent signaling modes – one associated with mTOR signaling and a second associated with ERK/Src signaling have been resolved, which in turn allow us to anticipate resistance, and to design combination therapies that are effective, as well as identify those therapies and therapy combinations that will be ineffective. We validated our predictions in mouse tumor models and all predictions were borne out.

In the last part, some preliminary results about the clinical translation of single-cell proteomics chips will be presented. The successful demonstration of our work on human-derived xenografts provides the rationale to extend our current work into the clinic. It will enable us to interrogate GBM tumor samples in a way that could potentially yield a straightforward, rapid interpretation so that we can give therapeutic guidance to the attending physicians within a clinical relevant time scale. The technical challenges of the clinical translation will be presented and our solutions to address the challenges will be discussed as well. A clinical case study will then follow, where some preliminary data collected from a pediatric GBM patient bearing an EGFR amplified tumor will be presented to demonstrate the general protocol and the workflow of the proposed clinical studies.

Processamento de Dados GNSS em Modo Cinemático

O princípio do posicionamento por GNSS baseia-se, resumidamente, na resolução de um problema matemático que envolve a observação das distâncias do utilizador a um conjunto de satélites com coordenadas conhecidas. A posição resultante pode ser calculada em modo absoluto ou relativo. O posicionamento absoluto necessita apenas de um recetor para a determinação da posição. Por sua vez, o posicionamento relativo implica a utilização de estações de referência e envolve a utilização de mais recetores para além do pertencente ao próprio utilizador. Assim, os métodos mais utilizados na determinação da posição de uma plataforma móvel, com exatidão na ordem dos centímetros, baseiam-se neste último tipo de posicionamento. Contudo, têm a desvantagem de estarem dependentes de estações de referência, com um alcance limitado, e requerem observações simultâneas dos mesmos satélites por parte da estação e do recetor. Neste sentido foi desenvolvida uma nova metodologia de posicionamento GNSS em modo absoluto, através da modelação ou remoção dos erros associados a cada componente das equações de observação, da utilização de efemérides precisas e correções aos relógios dos satélites. Este método de posicionamento tem a designação Precise Point Positioning (PPP) e permite manter uma elevada exatidão, equivalente à dos sistemas de posicionamento relativo. Neste trabalho, após um estudo aprofundado do tema, foi desenvolvida uma aplicação PPP, de índole académica, com recurso à biblioteca de classes C++ do GPS Toolkit, que permite determinar a posição e velocidade do recetor em modo cinemático e em tempo real. Esta aplicação foi ensaiada utilizando dados de observação de uma estação estática (processados em modo cinemático) e de uma estação em movimento instalada no NRP Auriga. Os resultados obtidos permitiram uma exatidão para a posição na ordem decimétrica e para a velocidade na ordem do cm/s.

Gimnasios inclusivos: “Diseño de interfaces de uso para la optimización de la interacción de personas con discapacidad en gimnasios regulares”

Esta tesis tiene dos objetivos, el primero es responder a la pregunta: ¿Cómo las personas con discapacidad pueden ser incluidos en los gimnasios regulares de la ciudad de Medellín y mediante la práctica de la actividad física aumentar su calidad de vida? -- El segundo objetivo es la aplicación de un proceso de diseño construido a partir de 3 metodologías: HCD Toolkit de IDEO, metodología de diseño y desarrollo de nuevos productos de Ulrich y Eppinger y las técnicas de ingeniería inversa y desarrollo de nuevos productos de Kevin otto y Kristin Wood, cuyo diferenciador es la ubicación de la usabilidad y la innovación social como eje transversal durante el proceso de diseño -- Para alcanzar estos objetivos, se diseñó una investigación aplicada y explicativa, en la que tuvieron participación medios documentales, de campo y de experimentación como libros, entrevistas, hallazgos guiados por la comunidad de personas con discapacidad en el gimnasio VIVO de la Universidad EAFIT y pruebas de uso de los productos diseñados con el usuario real en el contexto real; adicionalmente, esta tesis fue desarrollada bajo la modalidad de investigación cualitativa de acción en la que se tuvo contacto constante con la población y caso de estudio “población con discapacidad en gimnasios de la ciudad de Medellín” durante toda su ejecución, sin embargo, para efectos de la etapa de desarrollo de producto fue necesario aplicar la modalidad cuantitativa, por lo tanto tiene un carácter mixto -- Se realizó una investigación sobre las dificultades y necesidades que tenían las personas con discapacidad para acceder a un gimnasio regular, esto por medio de una validación en la que se llevó a dichos usuarios al gimnasio VIVO de la Universidad EAFIT donde luego del análisis del ejercicio de validación se identificó la necesidad de diseñar un kit de objetos de interacción que permitiera a las personas con discapacidad, usar los objetos de los gimnasios regulares, específicamente para la población con dificultades para agarrar como cuadripléjicos y artríticos; y para usuarios de sillas de ruedas con dificultades de equilibrio a la hora de interactuar con algunas de las máquinas -- El proceso de diseño aplicado para dicho desarrollo fue construido mediante la mezcla de tres metodologías diferentes mencionadas anteriormente y teniendo en cuenta la aplicación de la usabilidad y la innovación social como eje transversal del mismo proceso de creación -- Finalmente, se diseñó un freno para sillas de ruedas el cual evita que estas derriben al usuario hacia atrás cuando hace fuerza y un elemento tipo guante que reemplaza el agarre y la pinza gruesa de la mano; con estos objetos se logró que la mayoría de personas con dificultades para agarrar objetos o manijas puedan acceder a los gimnasios regulares y realizar una amplia serie de ejercicios con los que pueden aumentar la funcionalidad de su cuerpo y por tanto su calidad de vida

An adaptive neighborhood search algorithm for optimizing stochastic mining complexes

Les métaheuristiques sont très utilisées dans le domaine de l'optimisation discrète. Elles permettent d’obtenir une solution de bonne qualité en un temps raisonnable, pour des problèmes qui sont de grande taille, complexes, et difficiles à résoudre. Souvent, les métaheuristiques ont beaucoup de paramètres que l’utilisateur doit ajuster manuellement pour un problème donné. L'objectif d'une métaheuristique adaptative est de permettre l'ajustement automatique de certains paramètres par la méthode, en se basant sur l’instance à résoudre. La métaheuristique adaptative, en utilisant les connaissances préalables dans la compréhension du problème, des notions de l'apprentissage machine et des domaines associés, crée une méthode plus générale et automatique pour résoudre des problèmes. L’optimisation globale des complexes miniers vise à établir les mouvements des matériaux dans les mines et les flux de traitement afin de maximiser la valeur économique du système. Souvent, en raison du grand nombre de variables entières dans le modèle, de la présence de contraintes complexes et de contraintes non-linéaires, il devient prohibitif de résoudre ces modèles en utilisant les optimiseurs disponibles dans l’industrie. Par conséquent, les métaheuristiques sont souvent utilisées pour l’optimisation de complexes miniers. Ce mémoire améliore un procédé de recuit simulé développé par Goodfellow & Dimitrakopoulos (2016) pour l’optimisation stochastique des complexes miniers stochastiques. La méthode développée par les auteurs nécessite beaucoup de paramètres pour fonctionner. Un de ceux-ci est de savoir comment la méthode de recuit simulé cherche dans le voisinage local de solutions. Ce mémoire implémente une méthode adaptative de recherche dans le voisinage pour améliorer la qualité d'une solution. Les résultats numériques montrent une augmentation jusqu'à 10% de la valeur de la fonction économique.

Silicon Photonic Device for Wavelength Sensing and Monitoring

Over the last decade advances and innovations from Silicon Photonics technology were observed in the telecommunications and computing industries. This technology which employs Silicon as an optical medium, relies on current CMOS micro-electronics fabrication processes to enable medium scale integration of many nano-photonic devices to produce photonic integrated circuitry. However, other fields of research such as optical sensor processing can benefit from silicon photonics technology, specially in sensors where the physical measurement is wavelength encoded. In this research work, we present a design and application of a thermally tuned silicon photonic device as an optical sensor interrogator. The main device is a micro-ring resonator filter of 10 $\mu m$ of diameter. A photonic design toolkit was developed based on open source software from the research community. With those tools it was possible to estimate the resonance and spectral characteristics of the filter. From the obtained design parameters, a 7.8 x 3.8 mm optical chip was fabricated using standard micro-photonics techniques. In order to tune a ring resonance, Nichrome micro-heaters were fabricated on top of the device. Some fabricated devices were systematically characterized and their tuning response were determined. From measurements, a ring resonator with a free-spectral-range of 18.4 nm and with a bandwidth of 0.14 nm was obtained. Using just 5 mA it was possible to tune the device resonance up to 3 nm. In order to apply our device as a sensor interrogator in this research, a model of wavelength estimation using time interval between peaks measurement technique was developed and simulations were carried out to assess its performance. To test the technique, an experiment using a Fiber Bragg grating optical sensor was set, and estimations of the wavelength shift of this sensor due to axial strains yield an error within 22 pm compared to measurements from spectrum analyzer. Results from this study implies that signals from FBG sensors can be processed with good accuracy using a micro-ring device with the advantage of ts compact size, scalability and versatility. Additionally, the system also has additional applications such as processing optical wavelength shifts from integrated photonic sensors and to be able to track resonances from laser sources.

An adaptive neighborhood search algorithm for optimizing stochastic mining complexes

Les métaheuristiques sont très utilisées dans le domaine de l'optimisation discrète. Elles permettent d’obtenir une solution de bonne qualité en un temps raisonnable, pour des problèmes qui sont de grande taille, complexes, et difficiles à résoudre. Souvent, les métaheuristiques ont beaucoup de paramètres que l’utilisateur doit ajuster manuellement pour un problème donné. L'objectif d'une métaheuristique adaptative est de permettre l'ajustement automatique de certains paramètres par la méthode, en se basant sur l’instance à résoudre. La métaheuristique adaptative, en utilisant les connaissances préalables dans la compréhension du problème, des notions de l'apprentissage machine et des domaines associés, crée une méthode plus générale et automatique pour résoudre des problèmes. L’optimisation globale des complexes miniers vise à établir les mouvements des matériaux dans les mines et les flux de traitement afin de maximiser la valeur économique du système. Souvent, en raison du grand nombre de variables entières dans le modèle, de la présence de contraintes complexes et de contraintes non-linéaires, il devient prohibitif de résoudre ces modèles en utilisant les optimiseurs disponibles dans l’industrie. Par conséquent, les métaheuristiques sont souvent utilisées pour l’optimisation de complexes miniers. Ce mémoire améliore un procédé de recuit simulé développé par Goodfellow & Dimitrakopoulos (2016) pour l’optimisation stochastique des complexes miniers stochastiques. La méthode développée par les auteurs nécessite beaucoup de paramètres pour fonctionner. Un de ceux-ci est de savoir comment la méthode de recuit simulé cherche dans le voisinage local de solutions. Ce mémoire implémente une méthode adaptative de recherche dans le voisinage pour améliorer la qualité d'une solution. Les résultats numériques montrent une augmentation jusqu'à 10% de la valeur de la fonction économique.

Retos en la implementación de las normas internacionales al interior de los estados. estudio de caso: la región del Mekong y el protocolo de Palermo contra la trata de personas. (2007-2014)

El presente estudio de caso tiene como principal objetivo el de analizar la manera como las características sociopolíticas de los Estados del Mekong, específicamente en el caso de Camboya y Myanmar, dificultan la implementación de las normas enunciadas en el Protocolo de las Naciones Unidas para Prevenir, Reprimir y Sancionar la Trata de Personas, Especialmente Mujeres y Niños, también conocido como el Protocolo de Palermo. En este sentido, se parte de las características principales del Protocolo y de la manera como el tráfico de personas se presenta en el Mekong para posteriormente analizar la forma como la corrupción, la impunidad y la desigualdad de género representan retos sociopolíticos que obstruyen la implementación de los mandatos internacionales enmarcados en este instrumento

Condicionantes económicas de Colombia y la alianza del Pacífico

La principal finalidad de este estudio, es presentar una visión actualizada y genérica respecto a las condicionantes económicas de Colombia en particular y las relacionadas con el conjunto de países que conforman la Alianza del Pacífico en general –Chile, Colombia, México y Perú. Se trata de un estudio no experimental, descriptivo-interpretativo con énfasis en la revisión de datos. Entre las conclusiones más importantes se destacan los niveles de crecimiento económico con mayor estabilidad se presentan en Chile y Perú, una dependencia comercial exterior de México hacia Estados Unidos y que en Colombia se tiene el caso de que el aumento de producción que se hace evidente, no impacta tanto como era de esperarse, en la variable empleo.

Criação de uma framework para desenvolvimento de sistemas de comunicação aumentativa e alternativa

Nesta dissertação descreve-se uma proposta de implementação de uma plataforma de desenvolvimento de Sistemas de Comunicação Aumentativa e Alternativa para programadores, com o objectivo de melhorar a produtividade e diminuir os tempos despendidos na implementação deste tipo de soluções. Esta proposta assenta numa estrutura composta por widgets configuráveis por código e integráveis em novas aplicações, numa filosofia de reaproveitamento de objectos e funcionalidades, permitindo ainda a uniformização da estrutura do código no desenvolvimento de softwares deste tipo. Esta plataforma pretende ainda dar flexibilidade aos programadores, através da possibilidade de introdução de novas funcionalidades e widgets, permitindo também que se testem novas abordagens ao software durante a investigação. A implementação em tecnologias open source independentes da plataforma, permitirá ainda utilizar os objectos deste toolkit em vários sistemas operativos. ABSTRACT: ln this master thesis we describe an implementation proposal for an Augmentative and Alternative Communication Framework for developers, with the objective of improves the productivity and reduces the implementation times for these types of solutions. This proposal is based on a customized widgets structure that can be integrated in new applications, with the purpose of reuse common features of these applications, also allowing standardize the code structure in this kind of software development. This framework intends to provide flexibility to programmers giving them the possibility of introduce new functionalities and widgets, allowing them to test new approaches during research. The implementation based on open-source technologies, platform independent, allows the use of this toolkit in several different operating systems.