Comparative Study of Protein Unfolding in Aqueous Urea and Dimethyl Sulfoxide Solutions: Surface Polarity, Solvent Specificity, and Sequence of Secondary Structure Melting

Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here, we alter the solvent environment in a controlled manner by choosing two different cosolvents of water, urea, and dimethyl sulfoxide (DMSO) and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of alpha helices and beta sheets in these two solvents. For example, in 8 M urea solution, beta-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of alpha helices. In contrast, 8 M DMSO solution unfolds alpha helices first, followed by the separation of beta sheets for the majority of proteins. Sequence of unfolding events in four different alpha/beta proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.

Markov chain splitting methods in structural reliability integral estimation

Monte Carlo simulation methods involving splitting of Markov chains have been used in evaluation of multi-fold integrals in different application areas. We examine in this paper the performance of these methods in the context of evaluation of reliability integrals from the point of view of characterizing the sampling fluctuations. The methods discussed include the Au-Beck subset simulation, Holmes-Diaconis-Ross method, and generalized splitting algorithm. A few improvisations based on first order reliability method are suggested to select algorithmic parameters of the latter two methods. The bias and sampling variance of the alternative estimators are discussed. Also, an approximation to the sampling distribution of some of these estimators is obtained. Illustrative examples involving component and series system reliability analyses are presented with a view to bring out the relative merits of alternative methods. (C) 2015 Elsevier Ltd. All rights reserved.

薄板激光弯曲温度场的数值模拟与校验

采用MSC.Marc非线性有限元软件，对薄板激光变曲过程中的温度场进行了数值模拟，得到了引起薄板激光弯曲形的温度场的变化规律。通过温度传感器测量与激光扫描线相对应的薄板下表面温度变化的规律来验证数值模拟的结果。模拟值与实测值基本吻合，表明数值模拟结果可作为激光加工工艺参数选择的依据。

Quantum simulation of enzyme catalysis

Separating the dynamics of variables that evolve on different timescales is a common assumption in exploring complex systems, and a great deal of progress has been made in understanding chemical systems by treating independently the fast processes of an activated chemical species from the slower processes that proceed activation. Protein motion underlies all biocatalytic reactions, and understanding the nature of this motion is central to understanding how enzymes catalyze reactions with such specificity and such rate enhancement. This understanding is challenged by evidence of breakdowns in the separability of timescales of dynamics in the active site form motions of the solvating protein. Quantum simulation methods that bridge these timescales by simultaneously evolving quantum and classical degrees of freedom provide an important method on which to explore this breakdown. In the following dissertation, three problems of enzyme catalysis are explored through quantum simulation.

On the solution of first excursion problems by simulation with applications to probabilistic seismic performance assessment

In a probabilistic assessment of the performance of structures subjected to uncertain environmental loads such as earthquakes, an important problem is to determine the probability that the structural response exceeds some specified limits within a given duration of interest. This problem is known as the first excursion problem, and it has been a challenging problem in the theory of stochastic dynamics and reliability analysis. In spite of the enormous amount of attention the problem has received, there is no procedure available for its general solution, especially for engineering problems of interest where the complexity of the system is large and the failure probability is small.

The application of simulation methods to solving the first excursion problem is investigated in this dissertation, with the objective of assessing the probabilistic performance of structures subjected to uncertain earthquake excitations modeled by stochastic processes. From a simulation perspective, the major difficulty in the first excursion problem comes from the large number of uncertain parameters often encountered in the stochastic description of the excitation. Existing simulation tools are examined, with special regard to their applicability in problems with a large number of uncertain parameters. Two efficient simulation methods are developed to solve the first excursion problem. The first method is developed specifically for linear dynamical systems, and it is found to be extremely efficient compared to existing techniques. The second method is more robust to the type of problem, and it is applicable to general dynamical systems. It is efficient for estimating small failure probabilities because the computational effort grows at a much slower rate with decreasing failure probability than standard Monte Carlo simulation. The simulation methods are applied to assess the probabilistic performance of structures subjected to uncertain earthquake excitation. Failure analysis is also carried out using the samples generated during simulation, which provide insight into the probable scenarios that will occur given that a structure fails.

Análisis del proceso de Friction Drilling: Análisis de la calidad de la junta atornillada

[ES]En el presente trabajo, se pretende optimizar la unión atornillada de chapas de dos materiales disimilares (acero y aluminio) mediante un proceso no convencional, el taladrado por fricción. Dicho proceso está orientado a la calderería fina, sector en el cual tiene gran número de aplicaciones. Se comenzará con una serie de ensayos iníciales y se procederá a realizar pruebas sistemáticas. Se realizarán mediciones de temperaturas, momentos torsores y fuerzas, y se analizaran las tolerancias dimensionales generadas por el proceso para la elección de los parámetros óptimos. El documento se centrará en analizar de forma teórica el comportamiento mecánico de la unión y de los ensayos de tracción correspondientes. Esto servirá para realizar los futuros ensayos de calidad y posteriormente comparar los resultados con los de las uniones convencionales.

Análise de unidades de pré-purificação de ar por adsorção

Os principais constituintes do ar, nitrogênio, oxigênio e argônio, estão cada vez mais presentes nas indústrias, onde são empregados nos processos químicos, para o transporte de alimentos e processamento de resíduos. As duas principais tecnologias para a separação dos componentes do ar são a adsorção e a destilação criogênica. Entretanto, para ambos os processos é necessário que os contaminantes do ar, como o gás carbônico, o vapor dágua e hidrocarbonetos, sejam removidos para evitar problemas operacionais e de segurança. Desta forma, o presente trabalho trata do estudo do processo de pré-purificação de ar utilizando adsorção. Neste sistema a corrente de ar flui alternadamente entre dois leitos adsorvedores para produzir ar purificado continuamente. Mais especificamente, o foco da dissertação corresponde à investigação do comportamento de unidades de pré-purificação tipo PSA (pressure swing adsorption), onde a etapa de dessorção é realizada pela redução da pressão. A análise da unidade de pré-purificação parte da modelagem dos leitos de adsorção através de um sistema de equações diferenciais parciais de balanço de massa na corrente gasosa e no leito. Neste modelo, a relação de equilíbrio relativa à adsorção é descrita pela isoterma de Dubinin-Astakhov estendida para misturas multicomponentes. Para a simulação do modelo, as derivadas espaciais são discretizadas via diferenças finitas e o sistema de equações diferenciais ordinárias resultante é resolvido por um solver apropriado (método das linhas). Para a simulação da unidade em operação, este modelo é acoplado a um algoritmo de convergência relativo às quatro etapas do ciclo de operação: adsorção, despressurização, purga e dessorção. O algoritmo em questão deve garantir que as condições finais da última etapa são equivalentes às condições iniciais da primeira etapa (estado estacionário cíclico). Desta forma, a simulação foi implementada na forma de um código computacional baseado no ambiente de programação Scilab (Scilab 5.3.0, 2010), que é um programa de distribuição gratuita. Os algoritmos de simulação de cada etapa individual e do ciclo completo são finalmente utilizados para analisar o comportamento da unidade de pré-purificação, verificando como o seu desempenho é afetado por alterações nas variáveis de projeto ou operacionais. Por exemplo, foi investigado o sistema de carregamento do leito que mostrou que a configuração ideal do leito é de 50% de alumina seguido de 50% de zeólita. Variáveis do processo foram também analisadas, a pressão de adsorção, a vazão de alimentação e o tempo do ciclo de adsorção, mostrando que o aumento da vazão de alimentação leva a perda da especificação que pode ser retomada reduzindo-se o tempo do ciclo de adsorção. Mostrou-se também que uma pressão de adsorção maior leva a uma maior remoção de contaminantes.

Analog-digital and digital-analog converters using single-electron and MOS transistors

This paper proposes two kinds of novel single-electron analog-digital conversion (ADC) and digital-analog conversion (DAC) circuits that consist of single-electron transistors (SETs) and metal-oxide-semiconductor (MOS) transistors. The SET/MOS hybrid ADC and DAC circuits possess the merits of the SET circuit and the MOS circuit. We obtain the SPICE macro-modeling code of the SET transistor by studying and fitting the characteristics of the SET with SPICE simulation and Monte Carlo simulation methods. The SPICE macro-modeling code is used for the simulation of the SET/MOS hybrid ADC and DAC circuits. We simulate the performances of the SET/MOS hybrid 3-b ADC and 2-b DAC circuits by using the H-SPICE simulator. The simulation results demonstrate that the hybrid circuits can perform analog-digital and digital-analog data conversion well at room temperature. The hybrid ADC and DAC circuits have advantages as-follows: 1) compared with conventional circuits, the architectures of the circuits are simpler; 2) compared with single electron transistor circuits, the circuits have much larger load capability; 3) the power dissipation of the circuits are lower than uW; 4) the data conversion rate of the circuits can exceed 100 MHz; and 5) the resolution of the ADC and DAC circuits can be increased by the pipeline architectures.

The impact of virtual simulation in palliative radiotherapy for non-small-cell lung cancer.

Background and purpose: Radiotherapy is widely used to palliate local symptoms in non-small-cell lung cancer. Using conventional X-ray simulation, it is often difficult to accurately localize the extent of the tumour. We report a randomized, double blind trial comparing target localization with conventional and virtual simulation.Methods: Eighty-six patients underwent both conventional and virtual simulation. The conventional simulator films were compared with digitally reconstructed radiographs (DRRs) produced from the computed tomography (CT) data. The treatment fields defined by the clinicians using each modality were compared in terms of field area, position and the implications for target coverage.Results: Comparing fields defined by each study arm, there was a major mis-match in coverage between fields in 66.2% of cases, and a complete match in only 5.2% of cases. In 82.4% of cases, conventional simulator fields were larger (mean 24.5+/-5.1% (95% confidence interval)) than CT-localized fields, potentially contributing to a mean target under-coverage of 16.4+/-3.5% and normal tissue over-coverage of 25.4+/-4.2%.Conclusions: CT localization and virtual simulation allow more accurate definition of the target volume. This could enable a reduction in geographical misses, while also reducing treatment-related toxicity.

An intelligent configuration-sampling based local motion planner for robotic manipulators

Manipulator motion planning is a task which relies heavily on the construction of a configuration space prior to path planning. However when fast real-time motion is needed, the full construction of the manipulator's high-dimensional configu-ration space can be too slow and expensive. Alternative planning methods, which avoid this full construction of the manipulator's configuration space are needed to solve this problem. Here, one such existing local planning method for manipulators based on configuration-sampling and subgoal-selection has been extended. Using a modified Artificial Potential Fields (APF) function, goal-configuration sampling and a novel subgoal selection method, it provides faster, more optimal paths than the previously proposed work. Simulation results show a decrease in both runtime and path lengths, along with a decrease in unexpected local minimum and crashing issues.

Assisstantship improves medical student preparedness for starting work

Background: The GMC has recommended introducing student assistantships during which final year students, under supervision, undertake most of the responsibilities of a FY1 doctor. The Medical School at Queen’s University Belfast in 2011/12 introduced an assistantship programme. We have evaluated the impact of the assistantship on students’ perception of their preparedness for starting work.
Methods: Students were asked to complete a questionnaire at the beginning of the assistantship. It assessed the students’ perception of their preparedness in five areas: clinical and practical skills, communications skills, teaching and learning, understanding the work environment and team working. After the assistantship they again completed the questionnaire. Comparison of the results allowed an assessment of the impact of the assistantship.
Results: There was a statistically significant improvement in the students' perception of their preparation for 49 of 56 tasks contained within the questionnaire. After the assistantship 81.2% of students felt well prepared for starting work compared with 38.9% before the assistantship. 93.9% agreed that the assistantship had improved their preparedness for starting work.
Conclusions: The assistantship at Queen’s University improves medical students’ perception of their preparedness for starting work. The majority of medical students feel well prepared for starting work after completing the assistantship.

Metodologia bayesiana e adequação de modelos

Tese de doutoramento, Estatística e Investigação Operacional (Probabilidades e Estatística), Universidade de Lisboa, Faculdade de Ciências, 2014

Métodos probabilísticos e estatísticos na gestão de fogos florestais

Tese de doutoramento, Estatística e Investigação Operacional (Probabilidades e Estatística), Universidade de Lisboa, Faculdade de Ciências, 2014

Projecto de sistema de fixação de punções para quinadoras hidráulicas

Mestrado em Engenharia Mecânica - Construções Mecânicas