An optimal approach to the design of experiments for the automatic characterisation of biosystems

The Design-Build-Test-Learn cycle is the main approach of synthetic biology to re-design and create new biological parts and systems, targeting the solution for complex and challenging paramount problems. The applications of the novel designs range from biosensing and bioremediation of water pollutants (e.g. heavy metals) to drug discovery and delivery (e.g. cancer treatment) or biofuel production (e.g. butanol and ethanol), amongst others. Standardisation, predictability and automation are crucial elements for synthetic biology to efficiently attain these objectives. Mathematical modelling is a powerful tool that allows us to understand, predict, and control these systems, as shown in many other disciplines such as particle physics, chemical engineering, epidemiology and economics. Yet, the inherent difficulties of using mathematical models substantially slowed their adoption by the synthetic biology community. Researchers might develop different competing model alternatives in absence of in-depth knowledge of a system, consequently being left with the burden of with having to find the best one. Models also come with unknown and difficult to measure parameters that need to be inferred from experimental data. Moreover, the varying informative content of different experiments hampers the solution of these model selection and parameter identification problems, adding to the scarcity and noisiness of laborious-to-obtain data. The difficulty to solve these non-linear optimisation problems limited the widespread use of advantageous mathematical models in synthetic biology, broadening the gap between computational and experimental scientists. In this work, I present the solutions to the problems of parameter identification, model selection and experimental design, validating them with in vivo data. First, I use Bayesian inference to estimate model parameters, relaxing the traditional noise assumptions associated with this problem. I also apply information-theoretic approaches to evaluate the amount of information extracted from experiments (entropy gain). Next, I define methodologies to quantify the informative content of tentative experiments planned for model selection (distance between predictions of competing models) and parameter inference (model prediction uncertainty). Then, I use the two methods to define efficient platforms for optimal experimental design and use a synthetic gene circuit (the genetic toggle switch) to substantiate the results, computationally and experimentally. I also expand strategies to optimally design experiments for parameter identification to update parameter information and input designs during the execution of these (on-line optimal experimental design) using microfluidics. Finally, I developed an open-source and easy-to-use Julia package, BOMBs.jl, automating all the above functionalities to facilitate their dissemination and use amongst the synthetic biology community

The Influence of Seasonality on the Multi-Spectral Image Segmentation for Identification of Abandoned Land

Areas of agricultural land in Lithuania have decreased from 2005 to 2021 by up to 2.4%. Agricultural lands that are no longer used for their main purpose are very likely to become abandoned and the emergence of such lands can cause a variety of social, economic, and environmental problems. Therefore, it is very important to constantly monitor changes of abandoned agricultural lands. The purpose of the research is to analyse the influence of seasonality on image segmentation for the identification of abandoned land areas. Multi-spectral Sentinel-2 images from different periods (April, July, and September) and three supervised image segmentation methods (Spectral Angle Mapping (SAM), Maximum_Likelihood (ML), and Minimum distance (MD)) were used with the same parameters in this research. Studies had found that the most appropriate time to segment abandoned lands was in September, according to the SAM and ML algorithms. During this period, the intensity of the green colour was the highest and the colour brightness of abandoned lands differed from the colour intensity of other lands

Computational processing and analysis of ear images

Tese de mestrado. Engenharia Biomédica. Faculdade de Engenharia. Universidade do Porto. 201

Generative modeling of dynamic visual scenes

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 301-312).Modeling visual scenes is one of the fundamental tasks of computer vision. Whereas tremendous efforts have been devoted to video analysis in past decades, most prior work focuses on specific tasks, leading to dedicated methods to solve them. This PhD thesis instead aims to derive a probabilistic generative model that coherently integrates different aspects, notably appearance, motion, and the interaction between them. Specifically, this model considers each video as a composite of dynamic layers, each associated with a covering domain, an appearance template, and a flow describing its motion. These layers change dynamically following the associated flows, and are combined into video frames according to a Z-order that specifies their relative depth-order. To describe these layers and their dynamic changes, three major components are incorporated: (1) An appearance model describes the generative process of the pixel values of a video layer. This model, via the combination of a probabilistic patch manifold and a conditional Markov random field, is able to express rich local details while maintaining global coherence. (2) A motion model captures the motion pattern of a layer through a new concept called geometric flow that originates from differential geometric analysis. A geometric flow unifies the trajectory-based representation and the notion of geometric transformation to represent the collective dynamic behaviors persisting over time. (3) A partial Z-order specifies the relative depth order between layers. Here, through the unique correspondence between equivalent classes of partial orders and consistent choice functions, a distribution over the spaces of partial orders is established, and inference can thus be performed thereon. The development of these models leads to significant challenges in probabilistic modeling and inference that need new techniques to address. We studied two important problems: (1) Both the appearance model and the motion model rely on mixture modeling to capture complex distributions. In a dynamic setting, the components parameters and the number of components in a mixture model can change over time. While the use of Dirichlet processes (DPs) as priors allows indefinite number of components, incorporating temporal dependencies between DPs remains a nontrivial issue, theoretically and practically. Our research on this problem leads to a new construction of dependent DPs, enabling various forms of dynamic variations for nonparametric mixture models by harnessing the connections between Poisson and Dirichlet processes. (2) The inference of partial Z-order from a video needs a method to sample from the posterior distribution of partial orders. A key challenge here is that the underlying space of partial orders is disconnected, meaning that one may not be able to make local updates without violating the combinatorial constraints for partial orders. We developed a novel sampling method to tackle this problem, which dynamically introduces virtual states as bridges to connect between different parts of the space, implicitly resulting in an ergodic Markov chain over an augmented space. With this generative model of visual scenes, many vision problems can be readily solved through inference performed on the model. Empirical experiments demonstrate that this framework yields promising results on a series of practical tasks, including video denoising and inpainting, collective motion analysis, and semantic scene understanding.by Dahua Lin.Ph.D

Designing Statistical Language Learners: Experiments on Noun Compounds

The goal of this thesis is to advance the exploration of the statistical language learning design space. In pursuit of that goal, the thesis makes two main theoretical contributions: (i) it identifies a new class of designs by specifying an architecture for natural language analysis in which probabilities are given to semantic forms rather than to more superficial linguistic elements; and (ii) it explores the development of a mathematical theory to predict the expected accuracy of statistical language learning systems in terms of the volume of data used to train them. The theoretical work is illustrated by applying statistical language learning designs to the analysis of noun compounds. Both syntactic and semantic analysis of noun compounds are attempted using the proposed architecture. Empirical comparisons demonstrate that the proposed syntactic model is significantly better than those previously suggested, approaching the performance of human judges on the same task, and that the proposed semantic model, the first statistical approach to this problem, exhibits significantly better accuracy than the baseline strategy. These results suggest that the new class of designs identified is a promising one. The experiments also serve to highlight the need for a widely applicable theory of data requirements.Comment: PhD thesis (Macquarie University, Sydney; December 1995), LaTeX source, xii+214 page

Analyzing and Improving Statistical Language Models for Speech Recognition

In many current speech recognizers, a statistical language model is used to indicate how likely it is that a certain word will be spoken next, given the words recognized so far. How can statistical language models be improved so that more complex speech recognition tasks can be tackled? Since the knowledge of the weaknesses of any theory often makes improving the theory easier, the central idea of this thesis is to analyze the weaknesses of existing statistical language models in order to subsequently improve them. To that end, we formally define a weakness of a statistical language model in terms of the logarithm of the total probability, LTP, a term closely related to the standard perplexity measure used to evaluate statistical language models. We apply our definition of a weakness to a frequently used statistical language model, called a bi-pos model. This results, for example, in a new modeling of unknown words which improves the performance of the model by 14% to 21%. Moreover, one of the identified weaknesses has prompted the development of our generalized N-pos language model, which is also outlined in this thesis. It can incorporate linguistic knowledge even if it extends over many words and this is not feasible in a traditional N-pos model. This leads to a discussion of whatknowledge should be added to statistical language models in general and we give criteria for selecting potentially useful knowledge. These results show the usefulness of both our definition of a weakness and of performing an analysis of weaknesses of statistical language models in general.Comment: 140 pages, postscript, approx 500KB, if problems with delivery, mail to [email protected]

Cage active contours: Extension to color spaces and application to image morphing

The main purpose of this master thesis is to enhance the performance of Cage Active Contours (CAC) in the context of color image object segmentation as well as provide a theoretical framework on which to justify the potential applications of the segmentation produced in particular to image morphing