Recognition of short functional motifs in protein sequences

The main goal of this study was to develop a method for computational de novo prediction of short linear motifs (SLiMs) in protein sequences that would provide advantages over existing solutions for the users. The users are typically biological laboratory researchers, who want to elucidate the function of a protein that is possibly mediated by a short motif. Such a process can be subcellular localization, secretion, post-translational modification or degradation of proteins. Conducting such studies only with experimental techniques is often associated with high costs and risks of uncertainty. Preliminary prediction of putative motifs with computational methods, them being fast and much less expensive, provides possibilities for generating hypotheses and therefore, more directed and efficient planning of experiments. To meet this goal, I have developed HH-MOTiF – a web-based tool for de novo discovery of SLiMs in a set of protein sequences. While working on the project, I have also detected patterns in sequence properties of certain SLiMs that make their de novo prediction easier. As some of these patterns are not yet described in the literature, I am sharing them in this thesis. While evaluating and comparing motif prediction results, I have identified conceptual gaps in theoretical studies, as well as existing practical solutions for comparing two sets of positional data annotating the same set of biological sequences. To close this gap and to be able to carry out in-depth performance analyses of HH-MOTiF in comparison to other predictors, I have developed a corresponding statistical method, SLALOM (for StatisticaL Analysis of Locus Overlap Method). It is currently available as a standalone command line tool

Recognition of short functional motifs in protein sequences

The main goal of this study was to develop a method for computational de novo prediction of short linear motifs (SLiMs) in protein sequences that would provide advantages over existing solutions for the users. The users are typically biological laboratory researchers, who want to elucidate the function of a protein that is possibly mediated by a short motif. Such a process can be subcellular localization, secretion, post-translational modification or degradation of proteins. Conducting such studies only with experimental techniques is often associated with high costs and risks of uncertainty. Preliminary prediction of putative motifs with computational methods, them being fast and much less expensive, provides possibilities for generating hypotheses and therefore, more directed and efficient planning of experiments. To meet this goal, I have developed HH-MOTiF – a web-based tool for de novo discovery of SLiMs in a set of protein sequences. While working on the project, I have also detected patterns in sequence properties of certain SLiMs that make their de novo prediction easier. As some of these patterns are not yet described in the literature, I am sharing them in this thesis. While evaluating and comparing motif prediction results, I have identified conceptual gaps in theoretical studies, as well as existing practical solutions for comparing two sets of positional data annotating the same set of biological sequences. To close this gap and to be able to carry out in-depth performance analyses of HH-MOTiF in comparison to other predictors, I have developed a corresponding statistical method, SLALOM (for StatisticaL Analysis of Locus Overlap Method). It is currently available as a standalone command line tool

Holistic Vehicle Control Using Learning MPC

In recent years, learning MPC schemes have been introduced to address these challenges of traditional MPC. They typically leverage different machine learning techniques to learn the system dynamics directly from data, allowing it to handle model uncertainty more effectively. Besides, they can adapt to changes by continuously updating the learned model using real-time data, ensuring that the controller remains effective even as the system evolves. However, there are some challenges for the existing learning MPC techniques. Firstly, learning-based control approaches often lack interpretability. Understanding and interpreting the learned models and their learning and prediction processes are crucial for safety critical systems such as vehicle stability systems. Secondly, existing learning MPC techniques rely solely on learned models, which might result in poor performance or instability if the model encounters scenarios that differ significantly from the training data. Thirdly, existing learning MPC techniques typically require large amounts of high-quality data for training accurate models, which can be expensive or impractical in the vehicle stability control domain. To address these challenges, this thesis proposes a novel hybrid learning MPC approach for HVC. The main objective is to leverage the capabilities of machine learning algorithms to learn accurate and adaptive models of vehicle dynamics from data, enabling enhanced control strategies for improved stability and maneuverability. The hybrid learning MPC scheme maintains a traditional physics-based vehicle model and a data-based learning model. In the learned model, a variety of machine-learning techniques can be used to predict vehicle dynamics based on learning from collected vehicle data. The performance of the developed hybrid learning MPC controller using torque vectoring (TV) as the actuator is evaluated through the Matlab/Simulink and CarSim co-simulation with a high-fidelity Chevy Equinox vehicle model under a series of harsh maneuvers. Extensive real-world experiments using a Chevy Equinox electric testing vehicle are conducted. Both simulation results and experimental results show that the developed hybrid learning MPC approach consistently outperforms existing MPC methods with better yaw rate tracking performance and smaller vehicle sideslip under various driving conditions

Physical development and match analysis of elite youth soccer players

This thesis examined the physical development and match performance of elite youth academy soccer players some of whom were likely to progress to become professional soccer players. Physical characteristics such as standing height, body mass and estimated body fat composition, physical performance and match performance were explored. Furthermore, the relationships between physical performance and match running performance were examined in players from the U9 to U18 age group squads. Finally, the influence of biological maturity on physical characteristics, physical performance and match running performance in these elite youth soccer players was investigated and recommendations are made concerning talent identification and player development. One hundred and eighty-three elite soccer players (chronological age: 8.9 to 18.7 years; age grouping U9-U18) from an English Premier League Academy in the East Midlands were assessed for standing height, body mass, skinfolds, 30 m sprint, slalom and 505 agility, squat jump, counter movement jump with and without arms, Yo-Yo intermittent recovery test (level 1) and Multi-stage fitness test. All physical and performance variables measured in the study developed over time with chronological age except for the sum of 4 skinfold sites and estimated body fat composition (squad mean ± SD, U9 vs. U17: standing height, 139.4 ± 4.8 cm vs. 181.3 ± 5.6 cm; body mass, 33.6 ± 3.9 kg vs. 72.6 ± 5.7 kg; 30 m sprint, 5.26 ± 0.25 vs. 4.15 ± 0.11 s; slalom agility test, 4.83 ± 0.25 vs. 3.96 ± 0.09 s; counter movement jump with arms, 30 ± 3 cm vs. 48 ± 6 cm; the Yo-Yo intermittent recovery test (level 1), 787 ± 333 vs. 2617 ± 573 m). Standing height, body mass, 10, 15, and 30 m sprint times, performance on both agility tests, performance of squat jump and counter movement jump with arms; performance on the Yo-Yo intermittent recovery test (level 1) and on Multi-stage fitness test continued developing until the players reached the U17 squad. Moreover, the highest rate of development in standing height, body mass and all physical fitness tests occurred between the U9-U13 squads. Distance run during match play by 9 to 16 year old boys varied from 4056 (U9) to 7697 (U16) m per match (p < 0.05), and varied from 4675 to 6727 m∙hour-1 of a match (p < 0.05). The U11-U16 squads covered a greater distance by high speed running (range: 487-553 m∙hour-1) compared to the U9 (178 m∙hour-1) and U10 (219 m∙hour-1) squads (p < 0.05 for all). Similarly, the percentage of time spent in high speed running by the U9 (1.1 %) and U10 (1.3 %) squads was less than that seen in the U11-U16 (2.6-3.0 %) squads (p < 0.05 for all). Chronological age accounted for 43% (p < 0.01), and the Multi-stage fitness test performance explained 7% (p < 0.05) of the variance in total distance covered per hour of a match in the U11-U16 group. Chronological age (p < 0.01) and the Multi-stage fitness test performance (p < 0.05) accounted for 10% and 11% respectively of the variance in percentage of time spent in moderate speed running. Chronological age accounted for 11 % of the variance in the percentage of time spent in high speed running (p < 0.01), whereas 30 m sprint and the Multi-stage fitness test performances explained 15% and 8% respectively of the variance in percentage of time spent in high speed running (p < 0.05 for both). The U9 and U10 squads showed a positive relationship between 20 m sprint time and distance covered in moderate speed running per hour of a match (r = 0.54, p < 0.05). In the U11-U13 squads relationships were evident between performance in 5, 10, 15, 20 and 30 m sprint (r = -0.67 to -0.46), the 3 standing vertical jumps (r = 0.46 to 0.73) and the 2 endurance tests (r = 0.45 to 0.60), and distance covered by moderate and high speed running per hour of a match (p < 0.05 for all). However, in the U14-U16 squads no significant relationships were evident. When stage of genital development was used to categorise players, standing height and body mass in the U12, U13 and U14 squads were positively influenced by biological maturity (p < 0.05 for all). The more mature players in the U13 squad also performed better in counter movement jump without arms and the Multi-stage fitness test (p < 0.05 for both). When stage of pubic hair development was used to categorise players, maturity status showed a positive influence on standing height and slalom agility test performance in the U12 squad (p < 0.05 for both) and on standing height and body mass in the U14 squad (p < 0.05 for both). When estimated chronological age at peak height velocity was used to categorise players, earlier maturing players were heavier (p < 0.01) and performed worse in counter movement jump without arms (p < 0.05) than later maturers in the U9 and U10 squads. Earlier maturers were taller (p < 0.01), heavier (p < 0.01) and possessed a thicker sum of 4 skinfold sites (p < 0.05) and higher estimated body fat (p < 0.01) compared to the later maturers in the U11 and U12 squads. Moreover, early maturers covered a greater distance than late maturers in the multi-stage fitness test (p < 0.05) in the U13 and U14 squads. In the U15 and U16 squads, early maturers were heavier and possessed thicker sum of 4 skinfold sites and higher estimated body fat compared to the late maturers (p < 0.01 for all). Furthermore, early maturers possessed a thicker sum of 4 skinfold sites (p < 0.05), higher estimated body fat (p < 0.01) and covered a shorter distance during the Yo-Yo intermittent recovery test (p < 0.01) compared to later maturers in the U17 and U18 squads. When stage of genital development was used to categorise players, the U12 and U13 players in stage 4 covered a greater distance in high speed running during a match than players in stage 3 (p < 0.05). There was a tendency for this still to be the case when distance was standardised into per hour of a match (p = 0.065). In the U9 and U10 squads, compared to later maturers, earlier maturers were given greater playing time during a match (p < 0.05), and consequently covered a greater distance during match play (p < 0.05). In the U13 and U14 squads, earlier maturers covered more distance per hour of a match and spent a higher percentage of time in high speed running when compared to their later maturing counterparts (p < 0.05 for both). In summary this research has provided the most extensive description yet of the physical characteristics, field test performance and match performance of elite youth soccer players. In addition, for the first time the effect of biological maturity (using 3 different methods of assessment) on a wide range of field tests and on match performance has been reported. The major changes in physical characteristics, field test performance and match performance between 10 and 14 years of age suggest that coaches should avoid as many selection decisions as possible during this age period, that they should take into account the fact that match distances covered at high speeds will be affected by maturity at these ages and that they should be aware that at present, coaches choose to give more mature players additional pitch time which obviously gives them an advantage in terms of playing development. An enhanced awareness of these findings in the coaching community could lead to an improved development and more appropriate selection decisions for elite youth soccer players in England

Statistics and Evolution of Functional Genomic Sequence

In this thesis, three separate problems of genomics are addressed, utilizing methods related to the field of statistical mechanics. The goal of the project discussed in the first chapter is the elucidation of post-transcriptional gene regulation imposed by microRNAs, a recently discovered class of tiny non-coding RNAs. A probabilistic algorithm for the computational identification of genes regulated by microRNAs is introduced, which was developed based on experimental data and statistical analysis of whole genome data. In particular, the application of this algorithm to multiple-alignments of groups of related species allows for the specific and sensitive detection of genes targeted by microRNAs on a genome-wide level. Examination of clade-specific predictions and cross-clade comparison yields deeper insights into microRNA biology and first clues about long-term evolution of microRNA regulation, which are discussed in detail. Modeling evolutionary dynamics of microsatellites, an abundant class of repetitive sequence in eukaryotic genomes, was the objective of the second project and is discussed in chapter two. Inspired by the putative functionality of some of these elements and the difficulty of constructing correct sequence alignments that reflect the evolutionary relationships between microsatellites, a neutral model for microsatellite evolution is developed and tested in the fruit fly Drosophila melanogaster by comparing evolutionary rates predicted by the model to independent measurements of these rates from multiple alignments of three closely relates Drosophila species. The model is applied separately to genomic sequence categories of different functional annotations in order to assess the varying influence of selective constraint among these categories. In the last chapter, a general population genetic model is introduced that allows for the determination of transcription factor binding site stability as a function of selection strength, mutation rate and effective population size at arbitrary values of these parameters. The analytical solution of this model indicates the probability of a binding site to be functional. The model is used to compute the population fraction of functional binding sites at fixed selection pressure across a variety of different taxa. The results lead to the conclusion that a decreasing effective population size, such as observed at the evolutionary transition from prokaryotes to eukaryotes, could result in loss of binding site stability. An extension to our model serves us to assess the compensatory effect of the emergence of multiple binding sites for the same transcription factor in order to maintain the existing regulatory relationship

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Modelling change and stability of physical and technical performance in young soccer players.

Esta tese investigou a relação entre mudanças no crescimento e forma do corpo, composição corporal, maturação biológica, desempenho físico, habilidades técnicas, conhecimento de jogo e historial do treino de jovens futebolistas no contexto de seus clubes. O estudo tem um delineamento longitudinal-misto; amostrou 150 futebolistas com idades compreendidas entre os 12 e 14 anos no baseline, oriundos de seis clubes de futebol da área metropolitana do Porto que foram selecionados do estudo Em Busca da Excelência no Desporto - Um Estudo Longitudinal Misto em Jovens Atletas (INEX) (2016-2019). Os jogadores foram divididos em três coortes de idade (12, 13 e 14 anos), e seguidos consecutivamente durante 4 anos. Os dados foram coletados com protocolos padronizados, e a informação está dividida em dois domínios: Individual - biológico, aptidão física, habilidades específicas da modalidade/proficiência do jogo, psicológico, e contextual - clubes. Os procedimentos estatísticos foram realizados nos softwares Somatotype calculation, SPSS, Timepath, MATLAB e STATA. Os resultados mostraram que: (1) jogadores mais velhos são mais altos e pesados e têm valores de composição corporal correspondentes à maturação biológica avançada; (2) jogadores mais velhos têm melhor desempenho físico e são mais habilidosos que os seus pares mais jovens; (3) estas componentes estão relacionadas com maturidade avançada e mais tempo de treino; (4) as habilidades táticas e características psicológicas dos jogadores não diferem entre as coortes de idade; (5) os clubes oferecem uma variedade de condições para aumentar o sucesso dos jogadores na resposta ao treino e à competição; (6) o desenvolvimento da velocidade e agilidade apresentou uma tendência linear em função do tempo; (7) a puberdade é considerada um momento crucial para nutrir futuras vocações de qualidade dos jogadores de futebol dos futebolistas sobretudo no seu desempenho físico; (8) este desenvolvimento está positivamente associado com a maturidade, níveis mais elevados de força explosiva dos membros inferiores e horas acumuladas de treino; (9) velocidade de condução de bola, passe curto com tabela e o precisão de remate melhoraram com a idade, os níveis de atleticismo e horas acumuladas de treino; (10) o crescimento do corpo e a maturidade não explicaram, de forma independente, as diferenças nas trajetórias das habilidades técnicas dos jogadores; (11) o remate de precisão não está associado, significativamente, com os preditores considerados no estudo. Espera-se que os resultados deste estudo possam contribuir para uma atitude mais esclarecida e abrangente na preparação dos jovens futebolistas em termos da sua resposta ao treino e competição ao longo da sua carreira desportiva. PALAVRAS-CHAVE: futebol jovem; atuação; Habilidades; longitudinal; multinível; desenvolvimento; treino; maturidade.This thesis investigates the relationship between changes in young soccer players' physical growth, body shape and composition, biological maturation, physical performance, technical skills, game knowledge and training history within the context of their clubs. A total of 150 players aged 12 to 14 years, at baseline, were selected from participants in the In Search of Excellence in Sport - A Mixed-Longitudinal Study in Young Athletes (INEX) study (2016-2019). INEX was conducted in six soccer clubs of the Porto metropolitan area. They clustered into three age-cohorts (12, 13 and 14 years), were followed consecutively over 4-years using a mixed-longitudinal study design. All data were collected using standardized protocols and the information was distributed over two nested domains: individual - biological, skill/ game proficiency, psychological, and contexts - clubs. Statistical procedures were done in Somatotype calculation, SPSS, LDA, MATLAB, and STATA. Results showed that: (1) older players were more advanced in body physique and their body composition were in line with their advanced biological maturation; (2) older players outperformed their younger peers in all physical performance and technical skills components; (3) these components were related to both advanced maturity and increased training; (4) young soccer players' tactical skills as well as psychological characteristics did not differ across age-cohorts; (5) clubs offer a variety of conditions aiming to enhance players success in their response to training and competition; (6) young soccer players development in speed and agility showed a linear trend, i.e., they improve as time passes; (7) puberty has been found to be a crucial time for nourishing soccer players' future quality vocations in physical performance development; (8) physical performance development is positively associated with biological maturation, higher levels of explosive leg strength, and accumulated hours of soccer specific training; (9) dribbling speed, short-pass rebound and shooting accuracy linearly improved with age, levels of athleticism, and years of official soccer training had positive affect on dribbling speed development; (10) body growth and biological maturation did not independently explain differences in players' trajectories in technical skills; (11) shooting accuracy technique had no significant association with any predictors. We hope that these results may be useful for a more comprehensive approach in young soccer players' long-term preparation in terms of their responses to training and competition

Advances in Robotics, Automation and Control

The book presents an excellent overview of the recent developments in the different areas of Robotics, Automation and Control. Through its 24 chapters, this book presents topics related to control and robot design; it also introduces new mathematical tools and techniques devoted to improve the system modeling and control. An important point is the use of rational agents and heuristic techniques to cope with the computational complexity required for controlling complex systems. Through this book, we also find navigation and vision algorithms, automatic handwritten comprehension and speech recognition systems that will be included in the next generation of productive systems developed by man

Wearable Sensors Applied in Movement Analysis

Recent advances in electronics have led to sensors whose sizes and weights are such that they can be placed on living systems without impairing their natural motion and habits. They may be worn on the body as accessories or as part of the clothing and enable personalized mobile information processing. Wearable sensors open the way for a nonintrusive and continuous monitoring of body orientation, movements, and various physiological parameters during motor activities in real-life settings. Thus, they may become crucial tools not only for researchers, but also for clinicians, as they have the potential to improve diagnosis, better monitor disease development and thereby individualize treatment. Wearable sensors should obviously go unnoticed for the people wearing them and be intuitive in their installation. They should come with wireless connectivity and low-power consumption. Moreover, the electronics system should be self-calibrating and deliver correct information that is easy to interpret. Cross-platform interfaces that provide secure data storage and easy data analysis and visualization are needed.This book contains a selection of research papers presenting new results addressing the above challenges