Learning Models of Gene Expression from Synthetic DNA Sequences

Thesis (Ph.D.)--University of Washington, 2016-06

Adolescence: A useful concept for this millennium

‘Adolescence’ has become increasingly recognised as a nebulous concept. Previous conceptualisations of adolescence have adopted a ‘deficit’ view, regarding teenagers as ‘unfinished’ adults. The deficit view of adolescence is highly problematic in an era where adulthood itself is difficult to define. The terms ‘kidult’ or ‘adultescent’ have emerged to describe adult-age people whose interests and priorities match those of their teenage counterparts. Rather than relying on ‘lock-step’ models of physical, cognitive and social growth put forward by developmental psychology, adolescence can be more usefully defined by looking at the common experiences of people in their teenage years. Common experiences arise at an institutional level; for example, all adolescents are treated as the same by legal and education systems. The transition from primary to secondary schooling is a milestone for all children, exposing them to a new type of educational environment. Shared experiences also arise from generational factors. Today’s adolescents belong to the millennial generation, characterised by technological competence, global perspectives, high susceptibility to media influence, individualisation and rapid interactions. This generation focuses on teamwork, achievement, modesty and good conduct, and has great potential for significant collective accomplishments. These generational factors challenge educators to provide relevant learning experiences for today’s students. Many classrooms still utilise textbook-based pedagogy more suited to previous generations, resulting in disengagement among millennial students. Curriculum content must also be tailored to generational needs. The rapid pace of change, as well as the fluidity of identity created by dissolving geographical and vocational boundaries, mean that the millennial generation will need more than a fixed set of skills and knowledge to enter adulthood. Teachers must enable their students to think like ‘expert novices’, adept at assimilating new concepts in depth and prepared to engage in lifelong learning.

Topographic mappings and feed-forward neural networks

This thesis is a study of the generation of topographic mappings - dimension reducing transformations of data that preserve some element of geometric structure - with feed-forward neural networks. As an alternative to established methods, a transformational variant of Sammon's method is proposed, where the projection is effected by a radial basis function neural network. This approach is related to the statistical field of multidimensional scaling, and from that the concept of a 'subjective metric' is defined, which permits the exploitation of additional prior knowledge concerning the data in the mapping process. This then enables the generation of more appropriate feature spaces for the purposes of enhanced visualisation or subsequent classification. A comparison with established methods for feature extraction is given for data taken from the 1992 Research Assessment Exercise for higher educational institutions in the United Kingdom. This is a difficult high-dimensional dataset, and illustrates well the benefit of the new topographic technique. A generalisation of the proposed model is considered for implementation of the classical multidimensional scaling (¸mds}) routine. This is related to Oja's principal subspace neural network, whose learning rule is shown to descend the error surface of the proposed ¸mds model. Some of the technical issues concerning the design and training of topographic neural networks are investigated. It is shown that neural network models can be less sensitive to entrapment in the sub-optimal global minima that badly affect the standard Sammon algorithm, and tend to exhibit good generalisation as a result of implicit weight decay in the training process. It is further argued that for ideal structure retention, the network transformation should be perfectly smooth for all inter-data directions in input space. Finally, there is a critique of optimisation techniques for topographic mappings, and a new training algorithm is proposed. A convergence proof is given, and the method is shown to produce lower-error mappings more rapidly than previous algorithms.

Improved robust control of nonlinear stochastic systems using uncertain models

We introduce a technique for quantifying and then exploiting uncertainty in nonlinear stochastic control systems. The approach is suboptimal though robust and relies upon the approximation of the forward and inverse plant models by neural networks, which also estimate the intrinsic uncertainty. Sampling from the resulting Gaussian distributions of the inversion based neurocontroller allows us to introduce a control law which is demonstrably more robust than traditional adaptive controllers.

Variational inference for Student-t MLP models

This paper presents a novel methodology to infer parameters of probabilistic models whose output noise is a Student-t distribution. The method is an extension of earlier work for models that are linear in parameters to nonlinear multi-layer perceptrons (MLPs). We used an EM algorithm combined with variational approximation, the evidence procedure, and an optimisation algorithm. The technique was tested on two regression applications. The first one is a synthetic dataset and the second is gas forward contract prices data from the UK energy market. The results showed that forecasting accuracy is significantly improved by using Student-t noise models.

Techniques to improve forecasting models: applications to energy demand and price

This thesis is a study of three techniques to improve performance of some standard fore-casting models, application to the energy demand and prices. We focus on forecasting demand and price one-day ahead. First, the wavelet transform was used as a pre-processing procedure with two approaches: multicomponent-forecasts and direct-forecasts. We have empirically compared these approaches and found that the former consistently outperformed the latter. Second, adaptive models were introduced to continuously update model parameters in the testing period by combining ?lters with standard forecasting methods. Among these adaptive models, the adaptive LR-GARCH model was proposed for the fi?rst time in the thesis. Third, with regard to noise distributions of the dependent variables in the forecasting models, we used either Gaussian or Student-t distributions. This thesis proposed a novel algorithm to infer parameters of Student-t noise models. The method is an extension of earlier work for models that are linear in parameters to the non-linear multilayer perceptron. Therefore, the proposed method broadens the range of models that can use a Student-t noise distribution. Because these techniques cannot stand alone, they must be combined with prediction models to improve their performance. We combined these techniques with some standard forecasting models: multilayer perceptron, radial basis functions, linear regression, and linear regression with GARCH. These techniques and forecasting models were applied to two datasets from the UK energy markets: daily electricity demand (which is stationary) and gas forward prices (non-stationary). The results showed that these techniques provided good improvement to prediction performance.

Putting children forward for epilepsy surgery:a qualitative study of UK parents' and health professionals' decision-making experiences

Background Against a backdrop of recommendations for increasing access to and uptake of early surgical intervention for children with medically intractable epilepsy, it is important to understand how parents and professionals decide to put children forward for epilepsy surgery and what their decisional support needs are. Aim The aim of this study was to explore how parents and health professionals make decisions regarding putting children forward for pediatric epilepsy surgery. Methods Individual interviews were conducted with nine parents of children who had undergone pediatric epilepsy surgery at a specialist children's hospital and ten healthcare professionals who made up the children's epilepsy surgery service multidisciplinary healthcare team (MDT). Three MDT meetings were also observed. Data were analyzed thematically. Findings Four themes were generated from analysis of interviews with parents: presentation of surgery as a treatment option, decision-making, looking back, and interventions. Three themes were generated from analysis of interviews/observations with health professionals: triangulating information, team working, and patient and family perspectives. Discussion Parents wanted more information and support in deciding to put their child forward for epilepsy surgery. They attempted to balance the potential benefits of surgery against any risks of harm. For health professionals, a multidisciplinary approach was seen as crucial to the decision-making process. Advocating for the family was perceived to be the responsibility of nonmedical professionals. Conclusion Decision-making can be supported by incorporating families into discussions regarding epilepsy surgery as a potential treatment option earlier in the process and by providing families with additional information and access to other parents with similar experiences.

Kelet-közép-európai devizaárfolyamok előrejelzése határidős árfolyamok segítségével (Forecasting the exchange rates of three Central-Eastern European currencies with forward exchange rates)

Írásunkban azt vizsgáljuk, hogy a hosszú lejáratú határidős árfolyamok stacionaritását feltételező hibakorrekciós modellek, amelyeknek korábbi számítások szerint - a világ devizapiaci forgalmának mintegy 75 százalékát kitevő fejlett ipari országokra alkalmazva - kitűnő a mintán kívüli előrejelző erejük, hogyan képesek három keletközép- európai ország devizaárfolyamát előrejelezni. A három vizsgálat alá vont deviza (cseh, magyar, lengyel) esetében az eredmények relációnként nagyon eltérnek, és összességében kedvezőtlenebbek, mint a fejlett ipari országokra kapott eredmények, amit a nem teljesen rugalmas árfolyamrezsim, a rendelkezésre álló adatsor rövidsége, az eurózóna-csatlakozáshoz kapcsolódó bizonytalanságok, a devizakockázati és a határidős kamatprémium létezése, továbbá a Balassa-Samuelson-hatás együttes befolyásaként tudunk értelmezni. JEL kód: E43, F31, F47. /===/ This paper studies whether models that assume long-maturity forward exchange rates are stationary (which proved in earlier studies to provide superior forecasting ability when applied to exchange rates of major currencies) are capable of forecasting the Euro exchange rates of three Central-East European currencies (the Czech koruna, Hungarian forint and Polish zloty). The results for the three currencies differ from each other and are generally much worse than those obtained earlier for major currencies. These unfavourable results are attributed to the consequences of managed exchange-rate systems, to the short time series available, to uncertainties related to future Euro-zone entry, to the existence of a foreign exchange and term premium, and to the Balassa–Samuelson effect.

Development of an instrument to measure high school students' global awareness and attitudes: Looking through the lens of social sciences

The purpose of this study was to develop an instrument to measure high school students’ perspectives on global awareness and attitudes toward social issues. The research questions that guided this study were: (a) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' global awareness? (b) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' attitudes towards global social issues? (c) What is the relationship between high school students’ GPA, race/ethnicity, gender, socio-economic status, parents’ education, getting the news, reading and listening habits, the number of classes taken in the social sciences, whether they speak a second language, and have experienced living in or visiting other countries, and their perception of global awareness and attitudes toward global social issues. ^ An ex post facto research design was used and the data were collected using a 4-part Likert-type survey. It was administered to 14 schools in the Miami-Dade County, Florida area to 704 students. A factor analysis with an orthogonal varimax rotation was vii used to select the factors that best represented the three constructs – global education, global citizenship, and global workforce. This was done to establish construct validity. Cronbach’s alpha was used to determine the reliability of the instrument. Descriptive statistics and a hierarchical multiple regression were used for the demographics to establish their relationship, if any, to the findings. ^ Key findings of the study were that reliable and valid estimates can be developed for the instrument. The multiple regression analysis for model 1 and 2 accounted for a variance of 3% and 5% for self-perceptions of global awareness (factor 1). The regression model also accounted for a 5% and 13% variance in the two models for attitudes toward global social issues (factor 2). The demographics that were statistically significant were: ethnicity, gender, SES, parents’ education, listening to music, getting the news, speaking a second language, GPA, classes taken in the social sciences, and visiting other countries. An important finding for the study was those attending public schools (as opposed to private schools) had more positive attitudes towards global social issues (factor 2) The statistics indicated that these students had taken history, economics, and social studies – a curriculum infused with global perspectives.^

Modelagem matemática e experimental da perda de injetividade em poços canhoneados

Water injection in oil reservoirs is a recovery technique widely used for oil recovery. However, the injected water contains suspended particles that can be trapped, causing formation damage and injectivity decline. In such cases, it is necessary to stimulate the damaged formation looking forward to restore the injectivity of the injection wells. Injectivity decline causes a major negative impact to the economy of oil production, which is why, it is important to foresee the injectivity behavior for a good waterflooding management project. Mathematical models for injectivity losses allow studying the effect of the injected water quality, also the well and formation characteristics. Therefore, a mathematical model of injectivity losses for perforated injection wells was developed. The scientific novelty of this work relates to the modeling and prediction of injectivity decline in perforated injection wells, considering deep filtration and the formation of external cake in spheroidal perforations. The classic modeling for deep filtration was rewritten using spheroidal coordinates. The solution to the concentration of suspended particles was obtained analytically and the concentration of the retained particles, which cause formation damage, was solved numerically. The acquisition of the solution to impedance assumed a constant injection rate and the modified Darcy´s Law, defined as being the inverse of the normalized injectivity by the inverse of the initial injectivity. Finally, classic linear flow injectivity tests were performed within Berea sandstone samples, and within perforated samples. The parameters of the model, filtration and formation damage coefficients, obtained from the data, were used to verify the proposed modeling. The simulations showed a good fit to the experimental data, it was observed that the ratio between the particle size and pore has a large influence on the behavior of injectivity decline.

Source localization of reaction-diffusion models for brain tumors

We propose a mathematically well-founded approach for locating the source (initial state) of density functions evolved within a nonlinear reaction-diffusion model. The reconstruction of the initial source is an ill-posed inverse problem since the solution is highly unstable with respect to measurement noise. To address this instability problem, we introduce a regularization procedure based on the nonlinear Landweber method for the stable determination of the source location. This amounts to solving a sequence of well-posed forward reaction-diffusion problems. The developed framework is general, and as a special instance we consider the problem of source localization of brain tumors. We show numerically that the source of the initial densities of tumor cells are reconstructed well on both imaging data consisting of simple and complex geometric structures.

Extended nonlinear analytical models of compliant parallelogram mechanisms: third-order models

This paper proposes extended nonlinear analytical models, third-order models, of compliant parallelogram mechanisms. These models are capable of capturing the accurate effects from the very large axial force within the transverse motion range of 10% of the beam length through incorporating the terms associated with the high-order (up to third-order) axial force. Firstly, the free-body diagram method is employed to derive the nonlinear analytical model for a basic compliant parallelogram mechanism based on load-displacement relations of a single beam, geometry compatibility conditions, and load-equilibrium conditions. The procedures for the forward solutions and inverse solutions are described. Nonlinear analytical models for guided compliant multi-beam parallelogram mechanisms are then obtained. A case study of the compound compliant parallelogram mechanism, composed of two basic compliant parallelogram mechanisms in symmetry, is further implemented. This work intends to estimate the internal axial force change, the transverse force change, and the transverse stiffness change with the transverse motion using the proposed third-order model in comparison with the first-order model proposed in the prior art. In addition, FEA (finite element analysis) results validate the accuracy of the third-order model for a typical example. It is shown that in the case study the slenderness ratio affects the result discrepancy between the third-order model and the first-order model significantly, and the third-order model can illustrate a non-monotonic transverse stiffness curve if the beam is thin enough.

Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection

SELECTOR is a software package for studying the evolution of multiallelic genes under balancing or positive selection while simulating complex evolutionary scenarios that integrate demographic growth and migration in a spatially explicit population framework. Parameters can be varied both in space and time to account for geographical, environmental, and cultural heterogeneity. SELECTOR can be used within an approximate Bayesian computation estimation framework. We first describe the principles of SELECTOR and validate the algorithms by comparing its outputs for simple models with theoretical expectations. Then, we show how it can be used to investigate genetic differentiation of loci under balancing selection in interconnected demes with spatially heterogeneous gene flow. We identify situations in which balancing selection reduces genetic differentiation between population groups compared with neutrality and explain conflicting outcomes observed for human leukocyte antigen loci. These results and three previously published applications demonstrate that SELECTOR is efficient and robust for building insight into human settlement history and evolution.

Opinion: Can coalescent models explain deep divergences in the diatoms and argue for the acceptance of paraphyletic taxa at all taxonomic hierarchies?

Although ancestral polymorphisms and incomplete lineage sorting are commonly used at the population level, increasing reports of these models have been invoked and tested to explain deep radiations. Hypotheses are put forward for ancestral polymorphisms being the likely reason for paraphyletic taxa at the class level in the diatoms based on an ancient rapid radiation of the entire groups. Models for ancestral deep coalescence are invoked to explain paraphyly and molecular evolution at the class level in the diatoms. Other examples at more recent divergences are also documented. Discussion as to whether or not paraphyletic groups seen in the diatoms at all taxonomic levels should be recognized is provided. The continued use of the terms centric and pennate diatoms is substantiated with additional evidence produced to support their use in diatoms both as descriptive terms for both groups and as taxonomic groups for the latter because new morphological evidence from the auxospores justifies the formal classification of the basal and core araphids as new subclasses of pennate diatoms in the Class Bacillariophyceae. Keys for higher levels of the diatoms showing how the terms centrics and araphid diatoms can be defined are provided.

Opinion: Can coalescent models explain deep divergences in the diatoms and argue for the acceptance of paraphyletic taxa at all taxonomic hierarchies?

Although ancestral polymorphisms and incomplete lineage sorting are commonly used at the population level, increasing reports of these models have been invoked and tested to explain deep radiations. Hypotheses are put forward for ancestral polymorphisms being the likely reason for paraphyletic taxa at the class level in the diatoms based on an ancient rapid radiation of the entire groups. Models for ancestral deep coalescence are invoked to explain paraphyly and molecular evolution at the class level in the diatoms. Other examples at more recent divergences are also documented. Discussion as to whether or not paraphyletic groups seen in the diatoms at all taxonomic levels should be recognized is provided. The continued use of the terms centric and pennate diatoms is substantiated with additional evidence produced to support their use in diatoms both as descriptive terms for both groups and as taxonomic groups for the latter because new morphological evidence from the auxospores justifies the formal classification of the basal and core araphids as new subclasses of pennate diatoms in the Class Bacillariophyceae. Keys for higher levels of the diatoms showing how the terms centrics and araphid diatoms can be defined are provided.