614 research outputs found

    Pristup specifikaciji i generisanju proizvodnih procesa zasnovan na inženjerstvu vođenom modelima

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    In this thesis, we present an approach to the production process specification and generation based on the model-driven paradigm, with the goal to increase the flexibility of factories and respond to the challenges that emerged in the era of Industry 4.0 more efficiently. To formally specify production processes and their variations in the Industry 4.0 environment, we created a novel domain-specific modeling language, whose models are machine-readable. The created language can be used to model production processes that can be independent of any production system, enabling process models to be used in different production systems, and process models used for the specific production system. To automatically transform production process models dependent on the specific production system into instructions that are to be executed by production system resources, we created an instruction generator. Also, we created generators for different manufacturing documentation, which automatically transform production process models into manufacturing documents of different types. The proposed approach, domain-specific modeling language, and software solution contribute to introducing factories into the digital transformation process. As factories must rapidly adapt to new products and their variations in the era of Industry 4.0, production must be dynamically led and instructions must be automatically sent to factory resources, depending on products that are to be created on the shop floor. The proposed approach contributes to the creation of such a dynamic environment in contemporary factories, as it allows to automatically generate instructions from process models and send them to resources for execution. Additionally, as there are numerous different products and their variations, keeping the required manufacturing documentation up to date becomes challenging, which can be done automatically by using the proposed approach and thus significantly lower process designers' time.У овој дисертацији представљен је приступ спецификацији и генерисању производних процеса заснован на инжењерству вођеном моделима, у циљу повећања флексибилности постројења у фабрикама и ефикаснијег разрешавања изазова који се појављују у ери Индустрије 4.0. За потребе формалне спецификације производних процеса и њихових варијација у амбијенту Индустрије 4.0, креиран је нови наменски језик, чије моделе рачунар може да обради на аутоматизован начин. Креирани језик има могућност моделовања производних процеса који могу бити независни од производних система и тиме употребљени у различитим постројењима или фабрикама, али и производних процеса који су специфични за одређени систем. Како би моделе производних процеса зависних од конкретног производног система било могуће на аутоматизован начин трансформисати у инструкције које ресурси производног система извршавају, креиран је генератор инструкција. Такође су креирани и генератори техничке документације, који на аутоматизован начин трансформишу моделе производних процеса у документе различитих типова. Употребом предложеног приступа, наменског језика и софтверског решења доприноси се увођењу фабрика у процес дигиталне трансформације. Како фабрике у ери Индустрије 4.0 морају брзо да се прилагоде новим производима и њиховим варијацијама, неопходно је динамички водити производњу и на аутоматизован начин слати инструкције ресурсима у фабрици, у зависности од производа који се креирају у конкретном постројењу. Тиме што је у предложеном приступу могуће из модела процеса аутоматизовано генерисати инструкције и послати их ресурсима, доприноси се креирању једног динамичког окружења у савременим фабрикама. Додатно, услед великог броја различитих производа и њихових варијација, постаје изазовно одржавати неопходну техничку документацију, што је у предложеном приступу могуће урадити на аутоматизован начин и тиме значајно уштедети време пројектаната процеса.U ovoj disertaciji predstavljen je pristup specifikaciji i generisanju proizvodnih procesa zasnovan na inženjerstvu vođenom modelima, u cilju povećanja fleksibilnosti postrojenja u fabrikama i efikasnijeg razrešavanja izazova koji se pojavljuju u eri Industrije 4.0. Za potrebe formalne specifikacije proizvodnih procesa i njihovih varijacija u ambijentu Industrije 4.0, kreiran je novi namenski jezik, čije modele računar može da obradi na automatizovan način. Kreirani jezik ima mogućnost modelovanja proizvodnih procesa koji mogu biti nezavisni od proizvodnih sistema i time upotrebljeni u različitim postrojenjima ili fabrikama, ali i proizvodnih procesa koji su specifični za određeni sistem. Kako bi modele proizvodnih procesa zavisnih od konkretnog proizvodnog sistema bilo moguće na automatizovan način transformisati u instrukcije koje resursi proizvodnog sistema izvršavaju, kreiran je generator instrukcija. Takođe su kreirani i generatori tehničke dokumentacije, koji na automatizovan način transformišu modele proizvodnih procesa u dokumente različitih tipova. Upotrebom predloženog pristupa, namenskog jezika i softverskog rešenja doprinosi se uvođenju fabrika u proces digitalne transformacije. Kako fabrike u eri Industrije 4.0 moraju brzo da se prilagode novim proizvodima i njihovim varijacijama, neophodno je dinamički voditi proizvodnju i na automatizovan način slati instrukcije resursima u fabrici, u zavisnosti od proizvoda koji se kreiraju u konkretnom postrojenju. Time što je u predloženom pristupu moguće iz modela procesa automatizovano generisati instrukcije i poslati ih resursima, doprinosi se kreiranju jednog dinamičkog okruženja u savremenim fabrikama. Dodatno, usled velikog broja različitih proizvoda i njihovih varijacija, postaje izazovno održavati neophodnu tehničku dokumentaciju, što je u predloženom pristupu moguće uraditi na automatizovan način i time značajno uštedeti vreme projektanata procesa

    Evaluating Architectural Safeguards for Uncertain AI Black-Box Components

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    Although tremendous progress has been made in Artificial Intelligence (AI), it entails new challenges. The growing complexity of learning tasks requires more complex AI components, which increasingly exhibit unreliable behaviour. In this book, we present a model-driven approach to model architectural safeguards for AI components and analyse their effect on the overall system reliability

    Chatbots for Modelling, Modelling of Chatbots

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Escuela Politécnica Superior, Departamento de Ingeniería Informática. Fecha de Lectura: 28-03-202

    Measuring the impact of COVID-19 on hospital care pathways

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    Care pathways in hospitals around the world reported significant disruption during the recent COVID-19 pandemic but measuring the actual impact is more problematic. Process mining can be useful for hospital management to measure the conformance of real-life care to what might be considered normal operations. In this study, we aim to demonstrate that process mining can be used to investigate process changes associated with complex disruptive events. We studied perturbations to accident and emergency (A &E) and maternity pathways in a UK public hospital during the COVID-19 pandemic. Co-incidentally the hospital had implemented a Command Centre approach for patient-flow management affording an opportunity to study both the planned improvement and the disruption due to the pandemic. Our study proposes and demonstrates a method for measuring and investigating the impact of such planned and unplanned disruptions affecting hospital care pathways. We found that during the pandemic, both A &E and maternity pathways had measurable reductions in the mean length of stay and a measurable drop in the percentage of pathways conforming to normative models. There were no distinctive patterns of monthly mean values of length of stay nor conformance throughout the phases of the installation of the hospital’s new Command Centre approach. Due to a deficit in the available A &E data, the findings for A &E pathways could not be interpreted

    Coding by Design: GPT-4 empowers Agile Model Driven Development

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    Generating code from a natural language using Large Language Models (LLMs) such as ChatGPT, seems groundbreaking. Yet, with more extensive use, it's evident that this approach has its own limitations. The inherent ambiguity of natural language presents challenges for complex software designs. Accordingly, our research offers an Agile Model-Driven Development (MDD) approach that enhances code auto-generation using OpenAI's GPT-4. Our work emphasizes "Agility" as a significant contribution to the current MDD method, particularly when the model undergoes changes or needs deployment in a different programming language. Thus, we present a case-study showcasing a multi-agent simulation system of an Unmanned Vehicle Fleet. In the first and second layer of our approach, we constructed a textual representation of the case-study using Unified Model Language (UML) diagrams. In the next layer, we introduced two sets of constraints that minimize model ambiguity. Object Constraints Language (OCL) is applied to fine-tune the code constructions details, while FIPA ontology is used to shape communication semantics and protocols. Ultimately, leveraging GPT-4, our last layer auto-generates code in both Java and Python. The Java code is deployed within the JADE framework, while the Python code is deployed in PADE framework. Concluding our research, we engaged in a comprehensive evaluation of the generated code. From a behavioural standpoint, the auto-generated code aligned perfectly with the expected UML sequence diagram. Structurally, we compared the complexity of code derived from UML diagrams constrained solely by OCL to that influenced by both OCL and FIPA-ontology. Results indicate that ontology-constrained model produce inherently more intricate code, but it remains manageable and low-risk for further testing and maintenance

    Validation and Verification of Safety-Critical Systems in Avionics

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    This research addresses the issues of safety-critical systems verification and validation. Safety-critical systems such as avionics systems are complex embedded systems. They are composed of several hardware and software components whose integration requires verification and testing in compliance with the Radio Technical Commission for Aeronautics standards and their supplements (RTCA DO-178C). Avionics software requires certification before its deployment into an aircraft system, and testing is mandatory for certification. Until now, the avionics industry has relied on expensive manual testing. The industry is searching for better (quicker and less costly) solutions. This research investigates formal verification and automatic test case generation approaches to enhance the quality of avionics software systems, ensure their conformity to the standard, and to provide artifacts that support their certification. The contributions of this thesis are in model-based automatic test case generations approaches that satisfy MC/DC criterion, and bidirectional requirement traceability between low-level requirements (LLRs) and test cases. In the first contribution, we integrate model-based verification of properties and automatic test case generation in a single framework. The system is modeled as an extended finite state machine model (EFSM) that supports both the verification of properties and automatic test case generation. The EFSM models the control and dataflow aspects of the system. For verification, we model the system and some properties and ensure that properties are correctly propagated to the implementation via mandatory testing. For testing, we extended an existing test case generation approach with MC/DC criterion to satisfy RTCA DO-178C requirements. Both local test cases for each component and global test cases for their integration are generated. The second contribution is a model checking-based approach for automatic test case generation. In the third contribution, we developed an EFSM-based approach that uses constraints solving to handle test case feasibility and addresses bidirectional requirements traceability between LLRs and test cases. Traceability elements are determined at a low-level of granularity, and then identified, linked to their source artifact, created, stored, and retrieved for several purposes. Requirements’ traceability has been extensively studied but not at the proposed low-level of granularity

    Evaluating Architectural Safeguards for Uncertain AI Black-Box Components

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    Künstliche Intelligenz (KI) hat in den vergangenen Jahren große Erfolge erzielt und ist immer stärker in den Fokus geraten. Insbesondere Methoden des Deep Learning (ein Teilgebiet der KI), in dem Tiefe Neuronale Netze (TNN) zum Einsatz kommen, haben beeindruckende Ergebnisse erzielt, z.B. im autonomen Fahren oder der Mensch-Roboter-Interaktion. Die immense Datenabhängigkeit und Komplexität von TNN haben jedoch gravierende Schwachstellen offenbart. So reagieren TNN sensitiv auf bestimmte Einflussfaktoren der Umwelt (z.B. Helligkeits- oder Kontraständerungen in Bildern) und führen zu falschen Vorhersagen. Da KI (und insbesondere TNN) in sicherheitskritischen Systemen eingesetzt werden, kann solch ein Verhalten zu lebensbedrohlichen Situationen führen. Folglich haben sich neue Forschungspotenziale entwickelt, die sich explizit der Absicherung von KI-Verfahren widmen. Ein wesentliches Problem bei vielen KI-Verfahren besteht darin, dass ihr Verhalten oder Vorhersagen auf Grund ihrer hohen Komplexität nicht erklärt bzw. nachvollzogen werden können. Solche KI-Modelle werden auch als Black-Box bezeichnet. Bestehende Arbeiten adressieren dieses Problem, in dem zur Laufzeit “bösartige” Eingabedaten identifiziert oder auf Basis von Ein- und Ausgaben potenziell falsche Vorhersagen erkannt werden. Arbeiten in diesem Bereich erlauben es zwar potenziell unsichere Zustände zu erkennen, machen allerdings keine Aussagen, inwiefern mit solchen Situationen umzugehen ist. Somit haben sich eine Reihe von Ansätzen auf Architektur- bzw. Systemebene etabliert, um mit KI-induzierten Unsicherheiten umzugehen (z.B. N-Version-Programming-Muster oder Simplex Architekturen). Darüber hinaus wächst die Anforderung an KI-basierte Systeme sich zur Laufzeit anzupassen, um mit sich verändernden Bedingungen der Umwelt umgehen zu können. Systeme mit solchen Fähigkeiten sind bekannt als Selbst-Adaptive Systeme. Software-Ingenieure stehen nun vor der Herausforderung, aus einer Menge von Architekturellen Sicherheitsmechanismen, den Ansatz zu identifizieren, der die nicht-funktionalen Anforderungen bestmöglich erfüllt. Jeder Ansatz hat jedoch unterschiedliche Auswirkungen auf die Qualitätsattribute des Systems. Architekturelle Entwurfsentscheidungen gilt es so früh wie möglich (d.h. zur Entwurfszeit) aufzulösen, um nach der Implementierung des Systems Änderungen zu vermeiden, die mit hohen Kosten verbunden sind. Darüber hinaus müssen insbesondere sicherheitskritische Systeme den strengen (Qualitäts-) Anforderungen gerecht werden, die bereits auf Architektur-Ebene des Software-Systems adressiert werden müssen. Diese Arbeit befasst sich mit einem modellbasierten Ansatz, der Software-Ingenieure bei der Entwicklung von KI-basierten System unterstützt, um architekturelle Entwurfsentscheidungen (bzw. architekturellen Sicherheitsmechanismen) zum Umgang mit KI-induzierten Unsicherheiten zu bewerten. Insbesondere wird eine Methode zur Zuverlässigkeitsvorhersage von KI-basierten Systemen auf Basis von etablierten modellbasierten Techniken erforscht. In einem weiteren Schritt wird die Erweiterbarkeit/Verallgemeinerbarkeit der Zuverlässigkeitsvorhersage für Selbst-Adaptive Systeme betrachtet. Der Kern beider Ansätze ist ein Umweltmodell zur Modellierung () von KI-spezifischen Unsicherheiten und () der operativen Umwelt des Selbst-Adaptiven Systems. Zuletzt wird eine Klassifikationsstruktur bzw. Taxonomie vorgestellt, welche, auf Basis von verschiedenen Dimensionen, KI-basierte Systeme in unterschiedliche Klassen einteilt. Jede Klasse ist mit einem bestimmten Grad an Verlässlichkeitszusicherungen assoziiert, die für das gegebene System gemacht werden können. Die Dissertation umfasst vier zentrale Beiträge. 1. Domänenunabhängige Modellierung von KI-spezifischen Umwelten: In diesem Beitrag wurde ein Metamodell zur Modellierung von KI-spezifischen Unsicherheiten und ihrer zeitlichen Ausdehnung entwickelt, welche die operative Umgebung eines selbstadaptiven Systems bilden. 2. Zuverlässigkeitsvorhersage von KI-basierten Systemen: Der vorgestellte Ansatz erweitert eine existierende Architekturbeschreibungssprache (genauer: Palladio Component Model) zur Modellierung von Komponenten-basierten Software-Architekturen sowie einem dazugehörigenWerkzeug zur Zuverlässigkeitsvorhersage (für klassische Software-Systeme). Das Problem der Black-Box-Eigenschaft einer KI-Komponente wird durch ein Sensitivitätsmodell adressiert, das, in Abhängigkeit zu verschiedenen Unsicherheitsfaktoren, die Prädektive Unsicherheit einer KI-Komponente modelliert. 3. Evaluation von Selbst-Adaptiven Systemen: Dieser Beitrag befasst sich mit einem Rahmenwerk für die Evaluation von Selbst-Adaptiven Systemen, welche für die Absicherung von KI-Komponenten vorgesehen sind. Die Arbeiten zu diesem Beitrag verallgemeinern/erweitern die Konzepte von Beitrag 2 für Selbst-Adaptive Systeme. 4. Klassen der Verlässlichkeitszusicherungen: Der Beitrag beschreibt eine Klassifikationsstruktur, die den Grad der Zusicherung (in Bezug auf bestimmte Systemeigenschaften) eines KI-basierten Systems bewertet. Der zweite Beitrag wurde im Rahmen einer Fallstudie aus dem Bereich des Autonomen Fahrens validiert. Es wurde geprüft, ob Plausibilitätseigenschaften bei der Zuverlässigkeitsvorhersage erhalten bleiben. Hierbei konnte nicht nur die Plausibilität des Ansatzes nachgewiesen werden, sondern auch die generelle Möglichkeit Entwurfsentscheidungen zur Entwurfszeit zu bewerten. Für die Validierung des dritten Beitrags wurden ebenfalls Plausibilitätseigenschaften geprüft (im Rahmen der eben genannten Fallstudie und einer Fallstudie aus dem Bereich der Mensch-Roboter-Interaktion). Darüber hinaus wurden zwei weitere Community-Fallstudien betrachtet, bei denen (auf Basis von Simulatoren) Selbst-Adaptive Systeme bewertet und mit den Ergebnissen unseres Ansatzes verglichen wurden. In beiden Fällen konnte gezeigt werden, dass zum einen alle Plausibilitätseigenschaft erhalten werden und zum anderen, der Ansatz dieselben Ergebnisse erzeugt, wie die Domänen-spezifischen Simulatoren. Darüber hinaus konnten wir zeigen, dass unser Ansatz Software-Ingenieure bzgl. der Bewertung von Entwurfsentscheidungen, die für die Entwicklung von Selbst-Adaptiven Systemen relevant sind, unterstützt. Der erste Beitrag wurde implizit mit Beitrag 2 und mit 3 validiert. Für den vierten Beitrag wurde die Klassifikationsstruktur auf bekannte und repräsentative KI-Systeme angewandt und diskutiert. Es konnte jedes KI-System in eine der Klassen eingeordnet werden, so dass die generelle Anwendbarkeit der Klassifikationsstruktur gezeigt wurde

    Towards Intelligent Runtime Framework for Distributed Heterogeneous Systems

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    Scientific applications strive for increased memory and computing performance, requiring massive amounts of data and time to produce results. Applications utilize large-scale, parallel computing platforms with advanced architectures to accommodate their needs. However, developing performance-portable applications for modern, heterogeneous platforms requires lots of effort and expertise in both the application and systems domains. This is more relevant for unstructured applications whose workflow is not statically predictable due to their heavily data-dependent nature. One possible solution for this problem is the introduction of an intelligent Domain-Specific Language (iDSL) that transparently helps to maintain correctness, hides the idiosyncrasies of lowlevel hardware, and scales applications. An iDSL includes domain-specific language constructs, a compilation toolchain, and a runtime providing task scheduling, data placement, and workload balancing across and within heterogeneous nodes. In this work, we focus on the runtime framework. We introduce a novel design and extension of a runtime framework, the Parallel Runtime Environment for Multicore Applications. In response to the ever-increasing intra/inter-node concurrency, the runtime system supports efficient task scheduling and workload balancing at both levels while allowing the development of custom policies. Moreover, the new framework provides abstractions supporting the utilization of heterogeneous distributed nodes consisting of CPUs and GPUs and is extensible to other devices. We demonstrate that by utilizing this work, an application (or the iDSL) can scale its performance on heterogeneous exascale-era supercomputers with minimal effort. A future goal for this framework (out of the scope of this thesis) is to be integrated with machine learning to improve its decision-making and performance further. As a bridge to this goal, since the framework is under development, we experiment with data from Nuclear Physics Particle Accelerators and demonstrate the significant improvements achieved by utilizing machine learning in the hit-based track reconstruction process

    Reconfigurable Computing Systems for Robotics using a Component-Oriented Approach

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    Robotic platforms are becoming more complex due to the wide range of modern applications, including multiple heterogeneous sensors and actuators. In order to comply with real-time and power-consumption constraints, these systems need to process a large amount of heterogeneous data from multiple sensors and take action (via actuators), which represents a problem as the resources of these systems have limitations in memory storage, bandwidth, and computational power. Field Programmable Gate Arrays (FPGAs) are programmable logic devices that offer high-speed parallel processing. FPGAs are particularly well-suited for applications that require real-time processing, high bandwidth, and low latency. One of the fundamental advantages of FPGAs is their flexibility in designing hardware tailored to specific needs, making them adaptable to a wide range of applications. They can be programmed to pre-process data close to sensors, which reduces the amount of data that needs to be transferred to other computing resources, improving overall system efficiency. Additionally, the reprogrammability of FPGAs enables them to be repurposed for different applications, providing a cost-effective solution that needs to adapt quickly to changing demands. FPGAs' performance per watt is close to that of Application-Specific Integrated Circuits (ASICs), with the added advantage of being reprogrammable. Despite all the advantages of FPGAs (e.g., energy efficiency, computing capabilities), the robotics community has not fully included them so far as part of their systems for several reasons. First, designing FPGA-based solutions requires hardware knowledge and longer development times as their programmability is more challenging than Central Processing Units (CPUs) or Graphics Processing Units (GPUs). Second, porting a robotics application (or parts of it) from software to an accelerator requires adequate interfaces between software and FPGAs. Third, the robotics workflow is already complex on its own, combining several fields such as mechanics, electronics, and software. There have been partial contributions in the state-of-the-art for FPGAs as part of robotics systems. However, a study of FPGAs as a whole for robotics systems is missing in the literature, which is the primary goal of this dissertation. Three main objectives have been established to accomplish this. (1) Define all components required for an FPGAs-based system for robotics applications as a whole. (2) Establish how all the defined components are related. (3) With the help of Model-Driven Engineering (MDE) techniques, generate these components, deploy them, and integrate them into existing solutions. The component-oriented approach proposed in this dissertation provides a proper solution for designing and implementing FPGA-based designs for robotics applications. The modular architecture, the tool 'FPGA Interfaces for Robotics Middlewares' (FIRM), and the toolchain 'FPGA Architectures for Robotics' (FAR) provide a set of tools and a comprehensive design process that enables the development of complex FPGA-based designs more straightforwardly and efficiently. The component-oriented approach contributed to the state-of-the-art in FPGA-based designs significantly for robotics applications and helps to promote their wider adoption and use by specialists with little FPGA knowledge

    Regulatory Mechanisms of Gene Transcription in Escherichia Coli

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    Bacteria have always been exposed to a wide variety of environments, many of which are fluctuating. In order to survive in these environments, they have had to develop the ability to adapt to changing conditions, particularly hostile ones. The adaptiveness of these microorganisms primarily depends upon their gene regulatory mechanisms. Some of these are ‘local’, affecting only a few genes. For example, when a specific nutrient appears in the media, it activates a few genes. Other regulatory mechanisms are more complex, involving a large number of genes that need to be activated and/or repressed at specific time moments. The survival of bacterial species, in some cases, depends on the existence of diversity in their genes’ expression across the cell population, particularly since it is not always possible to predict the best action to take next. Understanding the mechanisms of bacteria that regulate the diversity in gene expression would help the bioindustries to benefit from them. Moreover, it would help finding ways to mitigate the harm caused by some species. Bacterial genes are primarily regulated by their promoter strength in recruiting RNAP and specificity to a σ factor and, in some cases, by one or more global regulators. In addition, many genes are also regulated by specific transcription factors that can act as activators or as repressors, when present. Aside from these, other influential factors are the supercoiling in the DNA region occupied by the gene, whether there are other promoters closely spaced to the promoter of interest and, if so, their orientation, etc (Dash, et al., 2021). This thesis focused on the study of some of the mechanisms that can affect genes’ transcription kinetics. We focused on three mechanisms: i) Building up of positive supercoils, ii) Transcription interference between closely spaced promoters in tandem formation, and iii) Global regulation by input transcription factors. First, we studied how the intrinsic and extrinsic sources of noise in gene expression could be regulated by tuning the relative duration of transcription initiation. The study was done using stochastic models. It was found that the diversity in transcription kinetics across a cell population increases with the increase in the relative duration of the closed complex formation. Second, a method was proposed to dissect the kinetics of transcription locking due to the effects of positive supercoiling buildup. Using RNA fluorescent protein tagging and microscopy, RNA transcripts were quantified in individual cells. It was found that increasing intracellular gyrase concentration decreases how often a promoter goes into the locked state, which in turn increases the gene’s transcription rate. Using that information, it is possible to infer how long the promoter is locked. Third, a method was proposed to quantify the RNA numbers in individual cells using information from flow cytometry. This method allows the quantification of RNA numbers in thousands of cells, and thus the mean and variability in those cells, with much less manual labour and in much lesser time than when using microscopy and image analysis. Fourth, a method was proposed to dissect the rate-liming steps of gene transcription regulated by promoters in tandem orientation. Using protein fusion library and flow cytometry, the protein abundance was quantified. It was found that the gene’s expression could be regulated by tuning the transcriptional interference by varying the promoters’ strength and the distance between the transcription start site of the promoters. Overall, the four studies above allow for, first, better extracting raw data from microscopy and flow cytometry, and from there, to either dissect the kinetics of rate- limiting steps during transcription initiation or, inversely, how they can be tuned to regulate the single-cell RNA and protein numbers. Having studied two core mechanisms regulating transcription, the fifth and final study focus on a third mechanism, which is transcription factor (TF) regulation. For this, we used RNA-seq to study how RNAP and TFs affect the kinetics of gene cohorts from measurements after RNAP shifts. We found that the magnitude of genes’ response is proportional to the asymmetry in the number of activators and repressors regulating them. Overall, the works conducted in this thesis show that the gene expression and its products diversity in cell populations can be regulated by varying the rate-limiting steps in transcription. These rate-limiting steps can be tuned by various mechanisms, such as the tuning of the accumulation of positive coils, tuning transcriptional interference of closely spaced promoters in tandem orientation and, tuning which and how many transcription factors act on each gene
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