Programming Molecular Devices using Nucleic Acid Hairpins

Nucleic Acid hairpins have been a subject of study for the last four decades. They are composed of single strand that is

hybridized to itself, and the central section forming an unhybridized loop. In nature, they stabilize single stranded RNA, serve as nucleation

sites for RNA folding, protein recognition signals, mRNA localization and regulation of mRNA degradation. On the other hand,

DNA hairpins in biological contexts have been studied with respect to forming cruciform structures that can regulate gene expression.

The use of DNA hairpins as fuel for synthetic molecular devices, including locomotion, was proposed and experimental demonstrated in 2003. They

were interesting because they bring to the table an on-demand energy/information supply mechanism.

The energy/information is hidden (from hybridization) in the hairpin’s loop, until required.

The energy/information is harnessed by opening the stem region, and exposing the single stranded loop section.

The loop region is now free for possible hybridization and help move the system into a thermodynamically favourable state.

The hidden energy and information coupled with

programmability provides another functionality, of selectively choosing what reactions to hide and

what reactions to allow to proceed, that helps develop a topological sequence of events.

Hairpins have been utilized as a source of fuel for many different DNA devices. In this thesis, we program four different

molecular devices using DNA hairpins, and experimentally validate them in the

laboratory. 1) The first device: A

novel enzyme-free autocatalytic self-replicating system composed entirely of DNA that operates isothermally. 2) The second

device: Time-Responsive Circuits using DNA have two properties: a) asynchronous: the final output is always correct

regardless of differences in the arrival time of different inputs.

b) renewable circuits which can be used multiple times without major degradation of the gate motifs

(so if the inputs change over time, the DNA-based circuit can re-compute the output correctly based on the new inputs).

3) The third device: Activatable tiles are a theoretical extension to the Tile assembly model that enhances

its robustness by protecting the sticky sides of tiles until a tile is partially incorporated into a growing assembly.

4) The fourth device: Controlled Amplification of DNA catalytic system: a device such that the amplification

of the system does not run uncontrollably until the system runs out of fuel, but instead achieves a finite

amount of gain.

Nucleic acid circuits with the ability

to perform complex logic operations have many potential practical applications, for example the ability to achieve point of care diagnostics.

We discuss the designs of our DNA Hairpin molecular devices, the results we have obtained, and the challenges we have overcome

to make these truly functional.

Design and analysis of a compliant parallel pan-tilt platform

In combination of the advantages of both parallel mechanisms and compliant mechanisms, a compliant parallel mechanism with two rotational DOFs (degrees of freedom) is designed to meet the requirement of a lightweight and compact pan-tilt platform. Firstly, two commonly-used design methods i.e. direct substitution and FACT (Freedom and Constraint Topology) are applied to design the configuration of the pan-tilt system, and similarities and differences of the two design alternatives are compared. Then inverse kinematic analysis of the candidate mechanism is implemented by using the pseudo-rigid-body model (PRBM), and the Jacobian related to its differential kinematics is further derived to help designer realize dynamic analysis of the 8R compliant mechanism. In addition, the mechanism’s maximum stress existing within its workspace is tested by finite element analysis. Finally, a method to determine joint damping of the flexure hinge is presented, which aims at exploring the effect of joint damping on actuator selection and real-time control. To the authors’ knowledge, almost no existing literature concerns with this issue.

Solvency considerations in the gamma-omega surplus model

Ce mémoire de maîtrise traite de la théorie de la ruine, et plus spécialement des modèles actuariels avec surplus dans lesquels sont versés des dividendes. Nous étudions en détail un modèle appelé modèle gamma-omega, qui permet de jouer sur les moments de paiement de dividendes ainsi que sur une ruine non-standard de la compagnie. Plusieurs extensions de la littérature sont faites, motivées par des considérations liées à la solvabilité. La première consiste à adapter des résultats d’un article de 2011 à un nouveau modèle modifié grâce à l’ajout d’une contrainte de solvabilité. La seconde, plus conséquente, consiste à démontrer l’optimalité d’une stratégie de barrière pour le paiement des dividendes dans le modèle gamma-omega. La troisième concerne l’adaptation d’un théorème de 2003 sur l’optimalité des barrières en cas de contrainte de solvabilité, qui n’était pas démontré dans le cas des dividendes périodiques. Nous donnons aussi les résultats analogues à l’article de 2011 en cas de barrière sous la contrainte de solvabilité. Enfin, la dernière concerne deux différentes approches à adopter en cas de passage sous le seuil de ruine. Une liquidation forcée du surplus est mise en place dans un premier cas, en parallèle d’une liquidation à la première opportunité en cas de mauvaises prévisions de dividendes. Un processus d’injection de capital est expérimenté dans le deuxième cas. Nous étudions l’impact de ces solutions sur le montant des dividendes espérés. Des illustrations numériques sont proposées pour chaque section, lorsque cela s’avère pertinent.

Dynamic Programming Approaches for Estimating and Applying Large-scale Discrete Choice Models

People go through their life making all kinds of decisions, and some of these decisions affect their demand for transportation, for example, their choices of where to live and where to work, how and when to travel and which route to take. Transport related choices are typically time dependent and characterized by large number of alternatives that can be spatially correlated. This thesis deals with models that can be used to analyze and predict discrete choices in large-scale networks. The proposed models and methods are highly relevant for, but not limited to, transport applications. We model decisions as sequences of choices within the dynamic discrete choice framework, also known as parametric Markov decision processes. Such models are known to be difficult to estimate and to apply to make predictions because dynamic programming problems need to be solved in order to compute choice probabilities. In this thesis we show that it is possible to explore the network structure and the flexibility of dynamic programming so that the dynamic discrete choice modeling approach is not only useful to model time dependent choices, but also makes it easier to model large-scale static choices. The thesis consists of seven articles containing a number of models and methods for estimating, applying and testing large-scale discrete choice models. In the following we group the contributions under three themes: route choice modeling, large-scale multivariate extreme value (MEV) model estimation and nonlinear optimization algorithms. Five articles are related to route choice modeling. We propose different dynamic discrete choice models that allow paths to be correlated based on the MEV and mixed logit models. The resulting route choice models become expensive to estimate and we deal with this challenge by proposing innovative methods that allow to reduce the estimation cost. For example, we propose a decomposition method that not only opens up for possibility of mixing, but also speeds up the estimation for simple logit models, which has implications also for traffic simulation. Moreover, we compare the utility maximization and regret minimization decision rules, and we propose a misspecification test for logit-based route choice models. The second theme is related to the estimation of static discrete choice models with large choice sets. We establish that a class of MEV models can be reformulated as dynamic discrete choice models on the networks of correlation structures. These dynamic models can then be estimated quickly using dynamic programming techniques and an efficient nonlinear optimization algorithm. Finally, the third theme focuses on structured quasi-Newton techniques for estimating discrete choice models by maximum likelihood. We examine and adapt switching methods that can be easily integrated into usual optimization algorithms (line search and trust region) to accelerate the estimation process. The proposed dynamic discrete choice models and estimation methods can be used in various discrete choice applications. In the area of big data analytics, models that can deal with large choice sets and sequential choices are important. Our research can therefore be of interest in various demand analysis applications (predictive analytics) or can be integrated with optimization models (prescriptive analytics). Furthermore, our studies indicate the potential of dynamic programming techniques in this context, even for static models, which opens up a variety of future research directions.

Towards convection-resolving, global atmospheric simulations with the Model for Prediction Across Scales (MPAS) v3.1: an extreme scaling experiment, links to sourcecode of model and grides

The Model for Prediction Across Scales (MPAS) is a novel set of Earth system simulation components and consists of an atmospheric model, an ocean model and a land-ice model. Its distinct features are the use of unstructured Voronoi meshes and C-grid discretisation to address shortcomings of global models on regular grids and the use of limited area models nested in a forcing data set, with respect to parallel scalability, numerical accuracy and physical consistency. This concept allows one to include the feedback of regional land use information on weather and climate at local and global scales in a consistent way, which is impossible to achieve with traditional limited area modelling approaches. Here, we present an in-depth evaluation of MPAS with regards to technical aspects of performing model runs and scalability for three medium-size meshes on four different high-performance computing (HPC) sites with different architectures and compilers. We uncover model limitations and identify new aspects for the model optimisation that are introduced by the use of unstructured Voronoi meshes. We further demonstrate the model performance of MPAS in terms of its capability to reproduce the dynamics of the West African monsoon (WAM) and its associated precipitation in a pilot study. Constrained by available computational resources, we compare 11-month runs for two meshes with observations and a reference simulation from the Weather Research and Forecasting (WRF) model. We show that MPAS can reproduce the atmospheric dynamics on global and local scales in this experiment, but identify a precipitation excess for the West African region. Finally, we conduct extreme scaling tests on a global 3?km mesh with more than 65 million horizontal grid cells on up to half a million cores. We discuss necessary modifications of the model code to improve its parallel performance in general and specific to the HPC environment. We confirm good scaling (70?% parallel efficiency or better) of the MPAS model and provide numbers on the computational requirements for experiments with the 3?km mesh. In doing so, we show that global, convection-resolving atmospheric simulations with MPAS are within reach of current and next generations of high-end computing facilities.

Automatically Evolving Rotation-invariant Texture Image Descriptors by Genetic Programming

In computer vision, training a model that performs classification effectively is highly dependent on the extracted features, and the number of training instances. Conventionally, feature detection and extraction are performed by a domain-expert who, in many cases, is expensive to employ and hard to find. Therefore, image descriptors have emerged to automate these tasks. However, designing an image descriptor still requires domain-expert intervention. Moreover, the majority of machine learning algorithms require a large number of training examples to perform well. However, labelled data is not always available or easy to acquire, and dealing with a large dataset can dramatically slow down the training process. In this paper, we propose a novel Genetic Programming based method that automatically synthesises a descriptor using only two training instances per class. The proposed method combines arithmetic operators to evolve a model that takes an image and generates a feature vector. The performance of the proposed method is assessed using six datasets for texture classification with different degrees of rotation, and is compared with seven domain-expert designed descriptors. The results show that the proposed method is robust to rotation, and has significantly outperformed, or achieved a comparable performance to, the baseline methods.

Climbing Up the Leaderboard: An Empirical Study of Applying Gamification Techniques to a Computer Programming Class

Conventional taught learning practices often experience difficulties in keeping students motivated and engaged. Video games, however, are very successful at sustaining high levels of motivation and engagement through a set of tasks for hours without apparent loss of focus. In addition, gamers solve complex problems within a gaming environment without feeling fatigue or frustration, as they would typically do with a comparable learning task. Based on this notion, the academic community is keen on exploring methods that can deliver deep learner engagement and has shown increased interest in adopting gamification – the integration of gaming elements, mechanics, and frameworks into non-game situations and scenarios – as a means to increase student engagement and improve information retention. Its effectiveness when applied to education has been debatable though, as attempts have generally been restricted to one-dimensional approaches such as transposing a trivial reward system onto existing teaching materials and/or assessments. Nevertheless, a gamified, multi-dimensional, problem-based learning approach can yield improved results even when applied to a very complex and traditionally dry task like the teaching of computer programming, as shown in this paper. The presented quasi-experimental study used a combination of instructor feedback, real time sequence of scored quizzes, and live coding to deliver a fully interactive learning experience. More specifically, the “Kahoot!” Classroom Response System (CRS), the classroom version of the TV game show “Who Wants To Be A Millionaire?”, and Codecademy’s interactive platform formed the basis for a learning model which was applied to an entry-level Python programming course. Students were thus allowed to experience multiple interlocking methods similar to those commonly found in a top quality game experience. To assess gamification’s impact on learning, empirical data from the gamified group were compared to those from a control group who was taught through a traditional learning approach, similar to the one which had been used during previous cohorts. Despite this being a relatively small-scale study, the results and findings for a number of key metrics, including attendance, downloading of course material, and final grades, were encouraging and proved that the gamified approach was motivating and enriching for both students and instructors.

Database evolution on an orthogonal persistent programming system: A semi-transparent approach

In this paper the problem of the evolution of an object-oriented database in the context of orthogonal persistent programming systems is addressed. We have observed two characteristics in that type of systems that offer particular conditions to implement the evolution in a semi-transparent fashion. That transparency can further be enhanced with the obliviousness provided by the Aspect-Oriented Programming techniques. Was conceived a meta-model and developed a prototype to test the feasibility of our approach. The system allows programs, written to a schema, access semi-transparently to data in other versions of the schema.

Issues and strategies in the parallelisation of unstructured multiphysics code

Unstructured mesh based codes for the modelling of continuum physics phenomena have evolved to provide the facility to model complex interacting systems. Such codes have the potential to provide a high performance on parallel platforms for a small investment in programming. The critical parameters for success are to minimise changes to the code to allow for maintenance while providing high parallel efficiency, scalability to large numbers of processors and portability to a wide range of platforms. The paradigm of domain decomposition with message passing has for some time been demonstrated to provide a high level of efficiency, scalability and portability across shared and distributed memory systems without the need to re-author the code into a new language. This paper addresses these issues in the parallelisation of a complex three dimensional unstructured mesh Finite Volume multiphysics code and discusses the implications of automating the parallelisation process.

ICTM: an interval tessellation-based model for reliable topographic segmentation

This work introduces a tessellation-based model for the declivity analysis of geographic regions. The analysis of the relief declivity, which is embedded in the rules of the model, categorizes each tessellation cell, with respect to the whole considered region, according to the (positive, negative, null) sign of the declivity of the cell. Such information is represented in the states assumed by the cells of the model. The overall configuration of such cells allows the division of the region into subregions of cells belonging to a same category, that is, presenting the same declivity sign. In order to control the errors coming from the discretization of the region into tessellation cells, or resulting from numerical computations, interval techniques are used. The implementation of the model is naturally parallel since the analysis is performed on the basis of local rules. An immediate application is in geophysics, where an adequate subdivision of geographic areas into segments presenting similar topographic characteristics is often convenient.

Dynamic multi-partitioning for parallel finite element applications

The central product of the DRAMA (Dynamic Re-Allocation of Meshes for parallel Finite Element Applications) project is a library comprising a variety of tools for dynamic re-partitioning of unstructured Finite Element (FE) applications. The input to the DRAMA library is the computational mesh, and corresponding costs, partitioned into sub-domains. The core library functions then perform a parallel computation of a mesh re-allocation that will re-balance the costs based on the DRAMA cost model. We discuss the basic features of this cost model, which allows a general approach to load identification, modelling and imbalance minimisation. Results from crash simulations are presented which show the necessity for multi-phase/multi-constraint partitioning components.

Temperature regulation of a pilot-scale batch reaction system via explicit model predictive control

In this paper, the temperature of a pilot-scale batch reaction system is modeled towards the design of a controller based on the explicit model predictive control (EMPC) strategy -- Some mathematical models are developed from experimental data to describe the system behavior -- The simplest, yet reliable, model obtained is a (1,1,1)-order ARX polynomial model for which the mentioned EMPC controller has been designed -- The resultant controller has a reduced mathematical complexity and, according to the successful results obtained in simulations, will be used directly on the real control system in a next stage of the entire experimental framework

Parallel ruptures: Jews of Bessarabia and Transnistria between Romanian nationalism and Soviet communism, 1918-1940

“Parallel Ruptures: Jews of Bessarabia and Transnistria between Romanian Nationalism and Soviet Communism, 1918-1940,” explores the political and social debates that took place in Jewish communities in Romanian-held Bessarabia and the Moldovan Autonomous Soviet Socialist Republic during the interwar era. Both had been part of the Russian Pale of Settlement until its dissolution in 1917; they were then divided by the Romanian Army’s occupation of Bessarabia in 1918 with the establishment of a well-guarded border along the Dniester River between two newly-formed states, Greater Romania and the Soviet Union. At its core, the project focuses in comparative context on the traumatic and multi-faceted confrontation with these two modernizing states: exclusion, discrimination and growing violence in Bessarabia; destruction of religious tradition, agricultural resettlement, and socialist re-education and assimilation in Soviet Transnistria. It examines also the similarities in both states’ striving to create model subjects usable by the homeland, as well as commonalities within Jewish responses on both sides of the border. Contacts between Jews on either side of the border remained significant after 1918 despite the efforts of both states to curb them, thereby necessitating a transnational view in order to examine Jewish political and social life in borderland regions. The desire among Jewish secular leaders to mold their co-religionists into modern Jews reached across state borders and ideological divides and sought to manipulate respective governments to establish these goals, however unsuccessful in the final analysis. Finally, strained relations between Jews in peripheral borderlands with those at national/imperial cores, Moscow and Bucharest, sheds light on the complex circumstances surrounding the inclusion versus exclusion debates at the heart of all interwar European states and the complicated negotiations that took place within all minority communities that responded to state policies.

Nonparametric tests of collectively rational consumption behavior: an integer programming procedure

We present an IP-based nonparametric (revealed preference) testing procedure for rational consumption behavior in terms of general collective models, which include consumption externalities and public consumption. An empirical application to data drawn from the Russia Longitudinal Monitoring Survey (RLMS) demonstrates the practical usefulness of the procedure. Finally, we present extensions of the testing procedure to evaluate the goodness-of-…t of the collective model subject to testing, and to quantify and improve the power of the corresponding collective rationality tests.

Separate compilation of structured documents

This paper draws a parallel between document preparation and the traditional processes of compilation and link editing for computer programs. A block-based document model is described which allows for separate compilation of various portions of a document. These portions are brought together and merged by a linker program, called dlink, whose pilot implementation is based on ditroff and on its underlying intermediate code. In the light of experiences with dlink the requirements for a universal object-module language for documents are discussed. These requirements often resemble the characteristics of the intermediate codes used by programming-language compilers but with interesting extra constraints which arise from the way documents are executed .