Philosophiae Doctor - PhD / This chapter outlines basic gene structure and how gene structure is related to promoter structure in both prokaryotes and eukaryotes and their transcription machinery. An in-depth discussion is given on variations types of the promoters among both prokaryotes and eukaryotes and as well as among three prokaryotic organisms namely, E.coli, B.subtilis and Mycobacteria with emphasis on Mituberculosis. The simplest definition that can be given for a promoter is: It is a segment of Deoxyribonucleic Acid (DNA) sequence located upstream of the 5' end of the gene where the RNA Polymerase enzyme binds prior to transcription (synthesis of RNA chain representative of one strand of the duplex DNA). However, promoters are more complex than defined above. For example, not all sequences upstream of genes can function as promoters even though they may have features similar to some known promoters (from section 1.2). Promoters are therefore specific sections of DNA sequences that are also recognized by specific proteins and therefore differ from other sections of DNA sequences that are transcribed or translated. The information for directing RNA polymerase to the promoter has to be in section of DNA sequence defining the promoter region. Transcription in prokaryotes is initiated when the enzyme RNA polymerase forms a complex with sigma factors at the promoter site. Before transcription, RNA polymerase must form a tight complex with the sigma/transcription factor(s) (figure 1.1). The 'tight complex' is then converted into an 'open complex' by melting of a short region of DNA within the sequence involved in the complex formation. The final step in transcription initiation involves joining of first two nucleotides in a phosphodiester linkage (nascent RNA) followed by the release of sigma/transcription factors. RNA polymerase then continues with the transcription by making a transition from initiation to elongation of the nascent transcript.

Notre objectif est de simuler des comportements multimodaux expressifs pour les agents conversationnels animés ACA. Ceux-ci sont des entités dotées de capacités affectives et communicationnelles; ils ont souvent une apparence humaine. Quand un ACA parle ou rit, il est capable de montrer de façon autonome des comportements multimodaux pour enrichir et compléter son discours prononcé et transmettre des informations qualitatives telles que ses émotions. Notre recherche utilise les modèles d’apprentissage à partir données. Un modèle de génération de comportements multimodaux pour un personnage virtuel parlant avec des émotions différentes a été proposé ainsi qu’un modèle de simulation du comportement de rire sur un ACA. Notre objectif est d'étudier et de développer des générateurs d'animation pour simuler la parole expressive et le rire d’un ACA. En partant de la relation liant prosodie de la parole et comportements multimodaux, notre générateur d'animation prend en entrée les signaux audio prononcés et fournit en sortie des comportements multimodaux. Notre travail vise à utiliser un modèle statistique pour saisir la relation entre les signaux donnés en entrée et les signaux de sortie; puis cette relation est transformée en modèle d’animation 3D. Durant l'étape d’apprentissage, le modèle statistique est entrainé à partir de paramètres communs qui sont composés de paramètres d'entrée et de sortie. La relation entre les signaux d'entrée et de sortie peut être capturée et caractérisée par les paramètres du modèle statistique. Dans l'étape de synthèse, le modèle entrainé est utilisé pour produire des signaux de sortie (expressions faciale, mouvement de tête et du torse) à partir des signaux d'entrée (F0, énergie de la parole ou pseudo-phonème du rire). La relation apprise durant la phase d'apprentissage peut être rendue dans les signaux de sortie. Notre module proposé est basé sur des variantes des modèles de Markov cachés (HMM), appelées HMM contextuels. Ce modèle est capable de capturer la relation entre les mouvements multimodaux et de la parole (ou rire); puis cette relation est rendue par l’animation de l’ACA. / Our aim is to render expressive multimodal behaviors for Embodied conversational agents, ECAs. ECAs are entities endowed with communicative and emotional capabilities; they have human-like appearance. When an ECA is speaking or laughing, it is capable of displaying autonomously behaviors to enrich and complement the uttered speech and to convey qualitative information such as emotion. Our research lies in the data-driven approach. It focuses on generating the multimodal behaviors for a virtual character speaking with different emotions. It is also concerned with simulating laughing behavior on an ECA. Our aim is to study and to develop human-like animation generators for speaking and laughing ECA. On the basis of the relationship linking speech prosody and multimodal behaviors, our animation generator takes as input human uttered audio signals and output multimodal behaviors. Our work focuses on using statistical framework to capture the relationship between the input and the output signals; then this relationship is rendered into synthesized animation. In the training step, the statistical framework is trained based on joint features, which are composed of input and of output features. The relation between input and output signals can be captured and characterized by the parameters of the statistical framework. In the synthesis step, the trained framework is used to produce output signals (facial expression, head and torso movements) from input signals (F0, energy for speech or pseudo-phoneme of laughter). The relation captured in the training phase can be rendered into the output signals. Our proposed module is based on variants of Hidden Markov Model (HMM), called Contextual HMM. This model is capable of capturing the relationship between human motions and speech (or laughter); then such relationship is rendered into the synthesized animations.

Media consumption has shown a tremendous increase in recent years, and with this increase, new audience expectations are put on the features offered by media-streaming services. One of these expectations is the ability to skip redundant content, which most probably is not of interest to the user. In this work, intro sequences which have sufficient length and a high degree of image similarity across all episodes of a show is targeted for detection. A statistical prediction model for classifying video intros based on these features was proposed. The model tries to identify frame similarities across videos from the same show and then filter out incorrect matches. The performance evaluation of the prediction model shows that the proposed solution for unguided predictions had an accuracy of 90.1%, and precision and recall rate of 93.8% and 95.8% respectively.The mean margin of error for a predicted start and end was 1.4 and 2.0 seconds. The performance was even better if the model had prior knowledge of one or more intro sequences from the same TV series confirmed by a human. However, due to dataset limitations the result is inconclusive. The prediction model was integrated into an automated system for processing internet videos available on SVT Play, and included administrative capabilities for correcting invalid predictions. / Under de senaste åren så har konsumtionen av TV-serier ökat markant och med det tillkommer nya förväntningar på den funktionalitet som erbjuds av webb-TVtjänster. En av dessa förväntningar är förmågan att kunna hoppa över redundant innehåll, vilket troligen inte är av intresse för användaren. I detta arbete så ligger fokus på att detektera video intron som bedöms som tillräckligt långa och har en hög grad av bildlighet över flera episoder från samma TV-program. En statistisk modell för att klassificera intron baserat på dessa egenskaper föreslogs. Modellen jämför bilder från samma TV-program för att försöka identifiera matchande sekvenser och filtrera bort inkorrekta matchningar. Den framtagna modellen hade en träffsäkerhet på 90.1%, precision på 93.8% och en återkallelseförmåga på 95.8%. Medelfelmarginalen uppgick till 1.4 sekunder för start och 2.0 sekunder för slut av ett intro. Modellen presterade bättre om den hade tillgång till en eller fler liknande introsekvenser från relaterade videor från sammaTV-program bekräftat av en människa. Eftersom datasetet som användes för testning hade vissa brister så ska resultatet endast ses som vägledande. Modellen integrerades i ett system som automatiskt processar internet videos frånSVT-Play. Ett tillhörande administrativt verktyg skapades även för att kunna rätta felaktiga gissningar.

This dissertation studies the effects of radiation-induced single-event upsets (SEUs) on field-programmable gate array(FPGA)-based circuits. It analyzes and quantifies a special case in data communication, that is, the synchronization issue of signals when they are sent across clock domains in triple modular redundancy (TMR) circuits with the presence of SEUs. After demonstrating that synchronizing errors cannot be eliminated in such case, this dissertation continues to present novel synchronizer designs that can guarantee reliable synchronization of triplicated signals. Fault injection tests then show that the proposed synchronizers provide between 6 and 10 orders of magnitude longer mean time to failure (MTTF) than unmitigated synchronizers. This dissertation also studies the reliability of block random access memory (BRAM) on FPGAs. By investigating several previous reliability models for single-error correction/double-error detection (SEC/DED) memory with scrubbing, this dissertation proposes two novel MTTF models that are suitable for FPGA applications. The first one considers non-uniform write rates for probabilistic write scrubbing, and the second one combines deterministic scrubbing and probabilistic scrubbing into a single model. The proposed models reveal the impact of memory access patterns on the reliability of BRAMs. Monte Carlo simulations then demonstrate the correctness of the proposed models. At last, the memory access patterns of a type of FPGA application, digital signal processing (DSP) is studied, and mitigation mechanisms for DSP applications are discussed.

Förståelse för naturligt språk, språk som har utvecklats av människan ex. talspråk eller teckenspråk, är en del av språkteknik. Det är ett brett ämnesområde där utvecklingen har gått fram i snabb takt senaste 20 åren. En bidragande faktor till denna utveckling är framgångarna med neurala nätverk som är en matematisk modell inspirerad av biologiska hjärnor. Förståelse för naturligt språk används inom många områden där det krävs att applikationer förstår innebörden av textinmatning. Exempel på applikationer som använder förståelse för naturligt språk är Google translate, Googles sökmotor och rättstavningsfunktionen i textredigerarprogram.   A Great Thing AB har utvecklat applikationen Thing Launcher. Thing Launcher är en applikation som hanterar andra applikationer med hjälp av användarens olika kriterier i samband mobilens olika funktionaliteter som; väder, geografisk position, tid mm. Ett exempel kan vara att användaren vill att Spotify ska spela en specifik låt när användaren kommer hem, eller att en taxi ska vara på plats när användaren anländer till en geografisk position.  I dagsläget styr man Thing Launcher med hjälp av textinmatningar. A Great Thing AB behöver hjälp att ta en prototyp på en motor med förståelse för naturligt språk som kan styras av både textinmatning och röstinmatning. Motorn ska användas i applikationen Thing Launcher. Med skalbarhet menas att motorn ska kunna utvecklas, att nya funktioner och applikationer ska kunna läggas till, samtidigt som systemet ska kunna vara i drift och att prestandan påverkas så lite som möjligt.   Detta examensarbete har som syfte att undersöka vilka algoritmer som är lämpliga för att bygga en skalbar motor med förståelse av naturligt språk. Utifrån detta utveckla en prototyp. En litteraturstudie gjordes mellan dolda Markovmodeller och neurala nätverk. Resultatet visade att neurala nätverk var överlägset i förståelse av naturligt språk. Flera typer av neurala nätverk finns implementerade i TensorFlow och den är mycket flexibelt med sitt bredda utbud av kompatibla mobila enheter, vilket nyttar utvecklingen med det modulära aspekten och därför valdes detta som ramverk för att utveckla prototypen. De två viktigaste komponenterna i prototypen bestod av Command tagger, som ska kunna identifiera vilken applikation som användaren vill styra och NER tagger, som ska identifiera vad användaren vill att applikationen ska utföra. För att mäta träffsäkerheten utfördes det två tester, en för respektive tagger, flera gånger som mätte hur ofta komponenterna gissade rätt efter varje träningsrunda. Varje träningsrunda bestod av att komponenterna fick tiotusentals meningar som de fick gissa på följt av facit för att ge feedback. Med hjälp av feedback kunde komponenterna anpassas för hur de agerar i framtiden i samma situation. Command tagger gissade rätt 94 procent av gångerna och Ner tagger gissade rätt 96 procent av gångerna efter de sista träningsrundorna. I prototypen användes Androids inbyggda mjukvara för taligenkänning. Det är en funktion som omvandlar ljudvågor till text. En serverbaserad lösning med REST applikationsgränssnitt utvecklades för att göra motorn skalbar.   Resultatet visar att fungerande prototyp som kan vidareutvecklas till en skalbar motor för naturligt språk. / Natural Language Understanding is a field that is part of Natural Language Processing. Big improvements have been made in the broad field of Natural Language Understanding during the past two decades. One big contribution to this is improvement is Neural Networks, a mathematical model inspired by biological brains. Natural Language Understanding is used in fields that require deeper understanding by applications. Google translate, Google search engine and grammar/spelling check are some examples of applications requiring deeper understanding. Thing Launcher is an application developed by A Great Thing AB. Thing Launcher is an application capable of managing other applications with different parameters. Some examples of parameters the user can use are geographic position and time. The user can as an example control what song will be played when you get home or order an Uber when you arrive to a certain destination. It is possible to control Thing Launcher today by text input. A Great Thing AB needs help developing a prototype capable of understanding text input and speech. The meaning of scalable is that it should be possible to develop, add functions and applications with as little impact as possible on up time and performance of the service. A comparison of suitable algorithms, tools and frameworks has been made in this thesis in order research what it takes to develop a scalable engine with the natural language understanding and then build a prototype from this gathered information. A theoretical comparison was made between Hidden Markov Models and Neural Networks. The results showed that Neural Networks are superior in the field of natural language understanding. The tests made in this thesis indicated that high accuracy could be achieved using neural networks. TensorFlow framework was chosen because it has many different types of neural network implemented in C/C++ ready to be used with Python and alsoand for the wide compatibility with mobile devices.  The prototype should be able to identify voice commands. The prototype has two important components called Command tagger, which is going to identify which application the user wants to control and NER tagger, which is the going to identify what the user wants to do. To calculate the accuracy, two types of tests, one for each component, was executed several times to calculate how often the components guessed right after each training iteration. Each training iteration consisted of giving the components thousands of sentences to guess and giving them feedback by then letting them know the right answers. With the help of feedback, the components were molded to act right in situations like the training. The tests after the training process resulted with the Command tagger guessing right 94% of the time and the NER tagger guessing right 96% of the time. The built-in software in Android was used for speech recognition. This is a function that converts sound waves to text. A server-based solution with REST interface was developed to make the engine scalability. This thesis resulted with a working prototype that can be used to further developed into a scalable engine.

Coronal Mass Ejections (CMEs) and solar flares are energetic events taking place at the Sun that can affect the space weather or the near-Earth environment by the release of vast quantities of electromagnetic radiation and charged particles. Solar active regions are the areas where most flares and CMEs originate. Studying the associations among sunspot groups, flares, filaments, and CMEs is helpful in understanding the possible cause and effect relationships between these events and features. Forecasting space weather in a timely manner is important for protecting technological systems and human life on earth and in space. The research presented in this thesis introduces novel, fully computerised, machine learning-based decision rules and models that can be used within a system design for automated space weather forecasting. The system design in this work consists of three stages: (1) designing computer tools to find the associations among sunspot groups, flares, filaments, and CMEs (2) applying machine learning algorithms to the associations¿ datasets and (3) studying the evolution patterns of sunspot groups using time-series methods. Machine learning algorithms are used to provide computerised learning rules and models that enable the system to provide automated prediction of CMEs, flares, and evolution patterns of sunspot groups. These numerical rules are extracted from the characteristics, associations, and time-series analysis of the available historical solar data. The training of machine learning algorithms is based on data sets created by investigating the associations among sunspots, filaments, flares, and CMEs. Evolution patterns of sunspot areas and McIntosh classifications are analysed using a statistical machine learning method, namely the Hidden Markov Model (HMM).

Gait analysis can improve our understanding of gait to improve medical diagnosis or treatment in clinical assessment. Studying the gait cycle in an embedded sensor system is essential for the detection of any abnormal walking pattern. This project aims to investigate several methods for gait phase recognition on embedded systems based on Hidden Markov Model (HMM) and Long short term memory (LSTM). This project proposes three methods, single HMM, multiple HMMs, and LSTM models, to identify the phase number in one gait. Single HMM has been constructed with the unit of gait via HMM learning. The corresponding phase number in the hidden state sequence can be selected for the observations via HMM decoding. Multiple HMMs have been constructed with the unit of phase instead of gait via HMM learning. The HMM evaluation can select the corresponding phase number in the hidden state sequence with the largest log- likelihood. Frame blocking and windowing function is also applied to evaluate these two methods. Estimation, validation, and forecast are implemented in the LSTM method as a benchmark. After comparing and evaluating the three methods for phase inference in terms of execution time, accuracy, and limitations, the method with multiple HMMs can provide satisfactory accuracy of gait phase number recognition in a relatively short time. It can be concluded that the multiple HMMs method may be more suitable for application in this phase inference scenario on the embedded sensor processing systems if the timing requirement is not so stringent. / Gånganalys kan förbättra vår förståelse för gång för att förbättra medicinsk diagnos eller behandling vid klinisk bedömning. Att studera gångcykeln i ett inbyggt sensorsystem är avgörande för detektering av onormalt gångmönster. Detta projekt syftar till att undersöka flera metoder för gångfasinferens på inbäddade system baserat på Hidden Markov Model (HMM) och Long short term memory (LSTM). I detta projekt har tre metoder, enstaka HMM, flera HMM och LSTM-modeller, föreslagits för att identifiera fasnumret i en gång. Enstaka HMM har konstruerats med gångenheten via HMM-lärande. Motsvarande fasnummer i den dolda tillståndssekvensen kan väljas för observationerna via HMM-avkodning. Flera HMM har konstruerats med fasenheten istället för gång via HMM-lärande. Motsvarande fasnummer i den dolda tillståndssekvensen kan väljas med störst logsannolikhet via HMM-utvärdering. Frame Blocking och Windowing-funktionen används också för att utvärdera dessa två metoder. Uppskattning, validering och prognos implementeras i LSTM-metoden som ett riktmärke. Efter att ha jämfört och utvärderat de tre metoderna för fasinferens när det gäller exekveringstid, noggrannhet och begränsningar kan metoden med flera HMM: er uppnå tillfredsställande noggrannhet för fasnummerigenkänning på relativt kort tid. Vi kan dra slutsatsen att den flera HMM-metoden kan vara mer lämplig för tillämpning i detta fasinferensscenario på de inbyggda sensorbehandlingssystemen om tidskravet inte är så strikt.

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Biological systems carry inherent complexity, which pose difficulties observing behavioural properties, such as diffusion coefficients, kinetic constants and state switching occurrences. With constantly improving computing power and microscopy technologies, single molecule methods have become a viable alternative when probing the behaviour of proteins, enzymes, lipids and other molecules. Processed microscopy images and videos provide information such as particle intensities and trajectories, avoiding ensemble averaging and therefore allowing for a detailed breakdown of particle mobility and interactions. A single particle tracking (SPT) algorithm was developed which implements detection, localization and position linking on image stacks. Sub-pixel precise detection is done via either centroid determination, Gaussian fit, or radial symmetry centres, while tracking makes use of distance based global cost optimization. The detection algorithm is also used for single particle spectroscopy, where intensity information is used to determine the size of oligomers, as well as their interaction with other molecules through channel intensity cross-correlation. The algorithm underwent benchmarking with simulated videos and was applied to three different biological systems with comparison to other established methods of analysis. The first system studied was the diffusion of the fluorescent lipophilic dye DiD in a five-component mitochondria-like solid-supported lipid bilayer. Comparing line-scanning fluorescence correlation spectroscopy (FCS) and single particle tracking, the measured diffusion coefficients were found to be statistically different, with DFCS = 3 μm2s-1 and DSPT = 2 μm2s-1, indicating different operational ranges for the two methods. FCS outperforms SPT when the diffusion coefficient exceeds 1 μm2s-1, making it ideal for lipid diffusion in fluid membranes and proteins in solution with weak membrane interaction. SPT is best suited for mobile and immobile membrane inserted proteins, as well as lipid diffusion in viscous membranes. The second system studied was the interaction between the two proteins Bax and Bid when inserted in a membrane. Bax and Bid are both members of the Bcl-2 family of proteins, which plays a vital role in the apoptosis mechanism, by inducing mitochondrial outer membrane permeabilization. To study this system with single particle spectroscopy, fluorescently labelled Bax and truncated Bid (tBid) were imaged when interacting with a mitochondria-like supported lipid bilayer with confocal microscopy. Immobile and mobile particles were detected and distinguished based on the eccentricity of the observed fluorescence spot. The intensity of the particle signal was used to determine oligomer type (homo-oligomerization) while the interaction with the particles' counterpart (hetero-oligomerization) was determined by channel cross-correlation. This allowed the measurement of the 2D-KD values for mobile (0.6 μm-2) and immobile (0.08 μm-2) Bax/tBid complexes, showing that the degree of insertion of the proteins in the membrane greatly affect their affinity for each other. The third and final system studied was the motion of cellulases on cellulose fibers. Enzymatic hydrolysis of crystalline cellulose is a costly step in the generation of fermentable sugars for biofuel production. Due to the complex structure and many possible interaction states of the enzymes with cellulose, single particle tracking is a well-adapted technique to the gathering of information on the enzyme dynamics, which is essential for process optimization. The movement of cellulases on cellulose substrate was observed via labelled Thermobifidia fusca Cel5A, Cel6B and Cel9A on bacterial micro-crystalline cellulose substrate. The detected trajectories were analyzed using multiple diffusion models. A simple one-state diffusion model was insufficient to describe the observed radial displacement distributions and so a two-state model was introduced and confronted with the data using conventional least-squares fits , as well as a hidden Markov approach. The diffusion coefficients of the two states are found to be on the order of Dfast = 10-3 μm2s-1 and Dslow = 10-4 μm2s-1, with the slow state being more stable and therefore more likely to occur. Single particle tracking can give us better insight into complex interactions, such as synergistic binding of proteins existing in several different states and processive enzymatic behaviour, where ensemble averaging techniques can fall short. The uses of single molecule methods are plentiful and with the current rise of machine learning, higher levels of abstraction will provide us with more detailed insights into biological processes, driving promising developments in the medical field, as well as new technologies in many sectors of industry. / Thesis / Doctor of Science (PhD) / Proteins are the motors that drive most cellular processes, for example steering a cell’s life cycle, or decomposing sources of nutrients. Being able to observe the motion of individual proteins is key to understanding their behaviour. In this work a single particle tracking (SPT) program was developed to extract protein trajectories from fluorescence microscopy experiments. With this tool-set we investigated the following two systems. The first system of interest is the Bcl-2 protein family, which is vital during the pro- grammed cell death at the end of each cell’s life span. The failure of a controlled cell death can have dire consequences, such as necrosis and cancer. The Bcl-2 family proteins Bid and Bax are active on the outer membrane of the mitochondria, where they initiate the process of terminating the cell’s functions by forming pores. For our experiments we ar- tificially mimicked the outer membrane of the mitochondria, introduced Bid and Bax and observed their preferential groupings on the membrane surface. This provided indications of the mechanisms involved during binding and pore formation. The motivation behind the investigation of the second system is the improvement of biofuel generation from a renewable source: plant-based biomass. Cellulases are enzymes from bacteria or fungi that break down cellulose – one of the main building blocks of all plant cell walls – into fermentable sugars. In fluorescence microscopy experiments a purified cellulose substrate was used to monitor the motion of three types of cellulases. The insight which we gained into the cellulase behaviour may allow the optimization of the process of cellulose decomposition.