Studying lymphocyte development using mass cytometry Abstract Development of mature lymphocytes, a white blood cell subtype, is crucial for the correct function of the human immune system. Currently, developmental pathways of lymphocytes can be studied using high-throughput single-cell measurements. In particular, mass cytometry enables the study of immunologically relevant pheno- typic and functional markers on a vast scale. In this work I present my individual contribution to tviblindi, a powerful software tool for analysis of cytometric data aimed at uncovering developmental trajectories. tviblindi is a package written in R, Python and C++. It provides a means to integrate prior knowledge with data analyses grounded in graph theory and algebraic topology. tviblindi is accessible to biological researchers without background in computer science or mathematics. It is an addition to the expanding field of trajectory inference in single-cell data. Furthermore, I review current knowledge of T-cell development and conduct a tviblindi analysis thereof using human thymus and peripheral blood datasets and evaluate the results. 1

This thesis proposes new algorithms for a group of sensing robots to learn a para- metric model for a dynamic spatio-temporal field, then based on the learned model trajectories are planned for sensing robots to best estimate the field. In this thesis we call these two parts learning and monitoring, respectively. For the learning, we first introduce a parametric model for the spatio-temporal field. We then propose a family of motion strategies that can be used by a group of mobile sensing robots to collect point measurements about the field. Our motion strategies are designed to collect enough information from enough locations at enough different times for the robots to learn the dynamics of the field. In conjunction with these motion strategies, we propose a new learning algorithm based on subspace identification to learn the parameters of the dynamical model. We prove that as the number of data collected by the robots goes to infinity, the parameters learned by our algorithm will converge to the true parameters. For the monitoring, based on the model learned from the learning part, three new informative trajectory planning algorithms are proposed for the robots to collect the most informative measurements for estimating the field. Kalman filter is used to calculate the estimate, and to compute the error covariance of the estimate. The goal is to find trajectories for sensing robots that minimize a cost metric on the error covariance matrix. We propose three algorithms to deal with this problem. First, we propose a new randomized path planning algorithm called Rapidly-exploring Random Cycles (RRC) and its variant RRC* to find periodic trajectories for the sensing robots that try to minimize the largest eigenvalue of the error covariance matrix over an infinite horizon. The algorithm is proven to find the minimum infinite horizon cost cycle in a graph, which grows by successively adding random points. Secondly, we apply kinodynamic RRT* to plan continuous trajectories to estimate the field. We formulate the evolution of the estimation error covariance matrix as a differential constraint and propose extended state space and task space sampling to fit this problem into classical RRT* setup. Thirdly, Pontryagin’s Minimum Principle is used to find a set of necessary conditions that must be satisfied by the optimal trajectory to estimate the field. We then consider a real physical spatio-temporal field, the surface water temper- ature in the Caribbean Sea. We first apply the learning algorithm to learn a linear dynamical model for the temperature. Then based on the learned model, RRC and RRC* are used to plan trajectories to estimate the temperature. The estimation performance of RRC and RRC* trajectories significantly outperform the trajectories planned by random search, greedy and receding horizon algorithms.

<p>Applied topology is a rapidly growing discipline aiming at using ideas coming from algebraic topology to solve problems in the real world, including analyzing point cloud data, shape analysis, etc. Semi-algebraic geometry deals with studying properties of semi-algebraic sets that are subsets of $\mathbb{R}^n$ and defined in terms of polynomial inequalities. Semi-algebraic sets are ubiquitous in applications in areas such as modeling, motion planning, etc. Developing efficient algorithms for computing topological invariants of semi-algebraic sets is a rich and well-developed field.</p> <p>However, applied topology has thrown up new invariants---such as persistent homology and barcodes---which give us new ways of looking at the topology of semi-algebraic sets. In this thesis, we investigate the interplay between these two areas. We aim to develop new efficient algorithms for computing topological invariants of semi-algebraic sets, such as persistent homology, and to develop new mathematical tools to make such algorithms possible.</p>

Bakgrund  Långvarig smärta är ett folkhälsoproblem som skapar lidande för den drabbade. Farmakologisk behandling ger inte alltid optimal effekt vilket kan leda till att personer med långvarig smärta söker sig till andra behandlingsmetoder. Därför behövs vidare forskning i de icke-farmakologiska behandlingsmetoderna för att få kunskap och information om den drabbades upplevelser av icke-farmakologisk behandling.  Syfte  Syftet var att belysa personers upplevelser av icke-farmakologisk behandling vid långvarig smärta.  Metod  En litteraturöversikt gjordes baserad på 15 vetenskapliga artiklar. Sökningen av litteratur genomfördes i två databaser CINAHL och PubMed. En kvalitetsgranskning av artiklarna utfördes med hjälp av Sophiahemmets bedömningsunderlag. Därefter gjordes en integrerad dataanalys där resultat från artiklarna analyserades och sammanställdes.  Resultat  Två huvudkategorier, Upplevd smärta och välbefinnande, samt sju subkategorier sammanställdes i resultatet. Resultat visade att icke-farmakologiska behandlingar ger en förbättring på smärtintensitet och ett ökat välmående inom både psykiska och fysiska funktioner.  Slutsats  Icke-farmakologiska behandlingsmetoder visades ha måttlig till god effekt på smärtintensitet. Smärtan försvann inte helt men en minskning i smärtintensitet gav plats för annat i personens liv, vilket ledde till en ökning i personens välmående som kan appliceras i sjuksköterskans arbete i omvårdnad av personer med långvarig smärta. / Background Persistent pain is a public health problem that creates suffering for the affected. Pharmacological treatment does not always give an optimal effect, which can lead to people with persistent pain seeking other treatment methods. Therefore, further research into the non-pharmacological treatment methods is needed in order to obtain knowledge and information about the experiences of those affected. Aim The aim was to shed light on people's experiences of non-pharmacological treatment in persistent pain. Method A literature review was made based on 15 scientific articles. The search for literature was conducted in two databases CINAHL and PubMed. A quality review of the articles was made with the help of Sophiahemmet's assessment basis. An integrated data analysis was then performed where results from the articles were analyzed and compiled. Results Two main categories, experienced pain and well-being, and seven sub-categories were compiled in the result. Results showed that non-pharmacological treatments provide an improvement in pain intensity and increased well-being in both mental and physical functions. Conclusions Non-pharmacological treatment methods have been shown to have a moderate to good effect on pain intensity. The pain did not disappear completely, but a decrease in pain intensity gave way to other things in the person's life, which led to an increase in the person's well-being that can apply in the nurse's work in caring for people with persistent pain.

Although sensor planning in computer vision has been a subject of research for over two decades, a vast majority of the research seems to concentrate on two particular applications in a rather limited context of laboratory and industrial workbenches, namely 3D object reconstruction and robotic arm manipulation. Recently, increasing interest is engaged in research to come up with solutions that provide wide-area autonomous surveillance systems for object characterization and situation awareness, which involves portable, wireless, and/or Internet connected radar, digital video, and/or infrared sensors. The prominent research problems associated with multisensor integration for wide-area surveillance are modality selection, sensor planning, data fusion, and data exchange (communication) among multiple sensors. Thus, the requirements and constraints to be addressed include far-field view, wide coverage, high resolution, cooperative sensors, adaptive sensing modalities, dynamic objects, and uncontrolled environments. This article summarizes a new survey and analysis conducted in light of these challenging requirements and constraints. It involves techniques and strategies from work done in the areas of sensor fusion, sensor networks, smart sensing, Geographic Information Systems (GIS), photogrammetry, and other intelligent systems where finding optimal solutions to the placement and deployment of multimodal sensors covering a wide area is important. While techniques covered in this survey are applicable to many wide-area environments such as traffic monitoring, airport terminal surveillance, parking lot surveillance, etc., our examples will be drawn mainly from such applications as harbor security and long-range face recognition.

Bulk atmospheric deposition samples were taken every two months for a year in 2009-2010 at two sites in northern Sweden and analyzed for a suite of legacy and emerging persistent organic chemicals including legacy organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs)  and novel flame retardants (NFRs).  To further investigate the urban occurrence and contribution to remote contamination of flame retardants, indoor air, ventilation system air, and dust were sampled in several microenvironments in Stockholm during the winter of 2012 for analysis of PBDEs, isomer-specific hexabromocyclododecane (HBCDD), and NFRs.  Outdoor air and soil samples were also sampled around the same time period for analysis of the same compounds.  Five emerging pollutants were detected in atmospheric deposition: the current-use pesticides trifluralin and chlorothalonil; and the NFRs 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), 1,2-bis(tribromophenoxy)ethane (BTBPE), and Dechlorane Plus (DP).  A decrease in the fraction of the anti isomer of DP was observed at the more remote site, indicating isomer-selective degradation or isomerization during long range atmospheric transport.  The more remote site also received more total deposition of organic pollutants despite its receiving less precipitation.  Although PBDEs and emerging organic pollutants were detected, the bulk of the deposition consisted of PCBs and hexachlorocyclohexanes (HCHs) at both sites.   Several NFRs were identified in indoor and ventilation air samples including TBECH, pentabromotoluene (PBT), hexabromobenzene (HBB), 1,2-bis(pentabromodiphenyl)ethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB), and bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (TBPH).  There was no significant difference between concentrations of contaminants in ventilation system air and indoor air indicating that the flame retardants included in this study reach the outdoor environment via ventilation systems.  Dust and outdoor air samples have only been analyzed for HBCDDs so far.  HBCDD concentrations in apartments, offices, and schools were lower than reported concentrations for other countries in similar microenvironments.   However, an enrichment of α-HBCDD compared to γ-HBCDD was observed in dust taken from near treated products in stores when compared to dust taken directly from those products.  Very low concentrations of HBCDDs were detected in outdoor air.

Tradition measures of recovery, such as patient-reported symptoms, objective measures such as balance, specific dimensions such as depression, fatigue, cognitive status, and exercise tolerance do not fully capture the impact of the concussion on performing individual activities and participating in life situations as experienced by the patient. No concussion-specific measure of functional status currently exists. Objectives The overarching purpose of this dissertation was to develop a concussion-specific measure of functional status. There were two specific objectives: 1. To examine the concept of functioning post-concussion; 2. To generate questionnaire items based on a conceptual model of functioning. Methods This dissertation follows the recommendations of the Association for Medical Education in Europe as a framework with which to meet the objectives. The first objective was addressed by (1) generating a list of concussion-specific concepts through a systematic review (Chapter 3), and (2) qualitative interviews with individuals with persistent post-concussion symptoms and clinicians with concussion expertise (Chapter 4). The relationships between the concepts that emerged from those studies are presented graphically in a conceptual model to meet the second objective. The concepts were then transformed into questionnaire items and pretested through cognitive interviews with individuals with PPCS and clinicians with concussion expertise. Finally, the questionnaire items were critically evaluated for proportion of shared content against existing measures used in concussion clinical trials by coding all items to the International Classification of Functioning, Disability and Health. Results Objective 1 Three main themes emerged from the qualitative findings: (1) functioning at the level of the individual and society; (2) environmental barriers and facilitators; and (3) capacity, defined as the length of time one could perform a task before the onset of symptoms, and the length of time it took to recovery from those symptoms. Objective 2 The final questionnaire is presented as the CORE-Q, which is comprised of 53 items over three complimentary subscales, namely the Post-Concussion Functional Scale, the Concussion Modifiers Scale, and the Global Functional Recovery Scale. Each subscale corresponds to one of the three main themes. No existing outcome measure contained more than 40% of the content within the CORE-Q, or 55% of any subscale. Conclusions The CORE-Q is a unique measure of functional status post-concussion that considers functioning from a biopsychosocial perspective. Further studies are needed to assess the psychometric properties of the CORE-Q before it is adopted into clinical practice and intervention trials.

Cette thèse propose une collection des nouveaux outils pour la représentation musicale. Ces modèles ont deux caractéristiques principales. D'un côté, ils sont inspirés par la géométrie et la topologie. De l'autre côté, ils ont une basse dimensionnalité, afin de garantir une visualisation intuitive des caractéristiques musicales qu'ils représentent. On s'est attaqué au problème de l'analyse musicale à partir de trois points de vue. On a représenté le contrepoint en utilisant des séries temporelles multivariées de matrices de permutations partielles. On a visualisé la conduite des voix en utilisant une classe particulière des tresses partielles et singulières. On donne ensuite une interpretation du Tonnetz comme complex simplicial et on utilise l'homologie persistante, afin de classifier des formes obtenues en déformant les sommets du Tonnetz. Ces déformations sont induites soit par des fonctions qui prennent en compte la nature symbolique de la musique, soit l'interaction symbol/signal. Les modèles basés sur la persistence topologique ont été testés sur une collection hétérogène de bases de données. Ces deux approches sont finalement combinées pour donner un troisième point de vue, qui a donné deux applications. Premièrement, on utilise l'alignement multiple des sequences, pour comparer plusieurs structures harmoniques et sémantiques déduites du signal audio, afin de visualiser et quantifier la propagation d’idée musicales entre artistes, genres et différentes époques. Ensuite on développe la théorie nécessaire pour comparer deux systèmes qui varient dans le temps, en représentant leurs caractéristiques géométriques comme des séries temporelles de diagrammes de persistence. / In this work, we suggest a collection of novel models for the representation of music. These models are endowed with two main features. First, they originate from a topological and geometrical inspiration; second, their low dimensionality allows to build simple and informative visualisations. We tackle the problem of music representation following three non-orthogonal directions. First, we propose an interpretation of counterpoint as a multivariate time series of partial permutation matrices, whose observations are characterised by a degree of complexity. After providing both a static and a dynamic representation of counterpoint, voice leadings are reinterpreted as a special class of partial singular braids, and their main features are visualised. Thereafter, we give a topological interpretation of the Tonnetz (a graph commonly used in computational musicology), whose vertices are deformed by both a harmonic and a consonance-oriented function. The shapes derived from these deformations are classified using the formalism of persistent homology. Thus, this novel representation of music is evaluated on a collection of heterogenous musical datasets. Finally, a combination of the two approaches is proposed. A model at the crossroad between the signal and symbolic analysis of music uses multiple sequences alignment to provide an encompassing, novel viewpoint on the musical inspiration transfer among compositions belonging to different artists, genres and time. Then, music is represented as a time series of topological fingerprints, allowing the comparison of pairs of time-varying shapes in both topological and musical terms.

Motivée par les travaux précédents sur la stabilisation de systèmes à excitation persistante, cette thèse s'intéresse à la stabilité et à la stabilisation de systèmes linéaires à commutation en dimensions finie et infinie. Après une introduction générale présentant les principales motivations et les résultats importants de la littérature, on aborde quatre sujets.On commence par l'étude d'un système linéaire en dimension finie à commutation aléatoire. Le temps passé en chaque sous-système $i$ est choisi selon une loi de probabilité ne dépendant que de $i$, les commutations entre sous-systèmes étant déterminées par une chaine de Markov discrète. On caractérise les exposants de Lyapunov en appliquant le Théorème Ergodique Multiplicatif d'Oseledets à un système associé en temps discret, et on donne une expression pour l'exposant de Lyapunov maximal. Ces résultats sont appliqués à un système de contrôle à commutation. Sous une hypothèse de contrôlabilité, on montre que ce système peut être stabilisé presque surement avec taux de convergence arbitraire, ce qui est en contraste avec les systèmes déterministes à excitation persistante.On considère ensuite un système de $N$ équations de transport avec amortissement interne à excitation persistante, couplées linéairement par le bord à travers une matrice $M$, ce qui peut être vu comme un système d'EDPs sur un réseau étoilé. On montre que, si l'activité de l'amortissement intermittent est déterminée par des signaux à excitation persistante, alors, sous des bonnes hypothèses sur $M$ et sur la rationalité des rapports entre les longueurs des arêtes du réseau, ce système est exponentiellement stable, uniformément par rapport aux signaux à excitation persistante. Ce résultat est montré grâce à une formule explicite pour les solutions du système, qui permet de bien suivre les effets de l'amortissement intermittent.Le sujet suivant que l'on considère est le comportement asymptotique d'équations aux différences non-autonomes. On obtient une formule explicite pour les solutions en termes des conditions initiales et de certains coefficients matriciels dépendants du temps, qui généralise la formule obtenue pour le système de $N$ équations de transport. Le comportement asymptotique des solutions est caractérisé à travers les coefficients matriciels. Dans le cas d'équations aux différences à commutation arbitraire, on obtient un résultat de stabilité qui généralise le critère de Hale--Silkowski pour les systèmes autonomes. Grâce à des transformations classiques d'EDPs hyperboliques en équations aux différences, on applique ces résultats au transport et à la propagation d'ondes sur des réseaux.Finalement, la formule explicite précédente est généralisée à une équation aux différences contrôlée, dont la contrôlabilité est alors analysée. La contrôlabilité relative est caractérisée à travers un critère algébrique sur les coefficients matriciels de la formule explicite, ce qui généralise le critère de Kalman. On compare également la contrôlabilité relative pour des retards différents en termes de leur structure de dépendance rationnelle, et on donne une borne sur le temps minimal de contrôlabilité. Pour des systèmes avec retards commensurables, on montre que la contrôlabilité exacte est équivalente à l'approchée et on donne un critère qui les caractérise. On analyse également la contrôlabilité exacte et approchée de systèmes en dimension $2$ avec deux retards sans l'hypothèse de commensurabilité. / Motivated by previous work on the stabilization of persistently excited systems, this thesis addresses stability and stabilization issues for linear switched systems in finite and infinite dimensions. After a general introduction presenting the main motivations and important results from the literature, we analyze four problems.The first system we study is a linear finite-dimensional random switched system. The time spend on each subsystem $i$ is chosen according to a probability law depending only on $i$, and the switches between subsystems are determined by a discrete Markov chain. We characterize the Lyapunov exponents by applying Oseledets' Multiplicative Ergodic Theorem to an associated discrete-time system, and provide an expression for the maximal Lyapunov exponent. These results are applied to a switched control system, showing that, under a controllability hypothesis, almost sure stabilization can be achieved with arbitrarily large decay rates, a situation in contrast to deterministic persistently excited systems.We next consider a system of $N$ transport equations with intermittent internal damping, linearly coupled by their boundary conditions through a matrix $M$, which can be seen as a system of PDEs on a star-shaped network. We prove that, if the activity of the intermittent damping terms is determined by persistently exciting signals, then, under suitable hypotheses on $M$ and on the rationality of the ratios between the lengths of the network edges, such system is exponentially stable, uniformly with respect to the persistently exciting signals. The proof of this result is based on an explicit representation formula for the solutions of the system, which allows one to efficiently track down the effects of the intermittent damping.The following topic we address is the asymptotic behavior of non-autonomous difference equations. We obtain an explicit representation formula for their solutions in terms of their initial conditions and some time-dependent matrix coefficients, which generalizes the one for the system of $N$ transport equations. The asymptotic behavior of solutions is characterized in terms of the matrix coefficients. In the case of difference equations with arbitrary switching, we obtain a stability result which generalizes Hale--Silkowski criterion for autonomous systems. Using classical transformations of hyperbolic PDEs into difference equations, we apply our results to transport and wave propagation on networks.Finally, we generalize the previous representation formula to a controlled difference equation, whose controllability is then analyzed. Relative controllability is characterized in terms of an algebraic property on the matrix coefficients from the explicit formula, generalizing Kalman criterion. We also compare the relative controllability for different delays in terms of their rational dependence structure, and provide a bound on the minimal controllability time. Exact and approximate controllability for systems with commensurable delays are characterized and proved to be equivalent. We also describe exact and approximate controllability for two-dimensional systems with two delays not necessarily commensurable.

As cyber criminals can find many different ways of gaining unauthorized access to systems without being detected, it is of high importance for organizations to monitor what is happening inside their systems. Adversary emulation is a way to mimic behavior of advanced adversaries within cyber security, which can be used to test detection capabilities of malicious behavior within a system of an organization. The emulated behavior can be based on what have been observed in real cyber attacks - open source knowledge bases such as MITRE ATT&amp;CK collect this kind of intelligence. Many organizations have in recent years developed tools to simplify emulating the behavior of known adversaries. These tools are referred to as adversary emulation tools in this thesis. The purpose of this thesis was to evaluate how noisy different adversary emulation tools are. This was done through measurements on the amount of event logs generated by Sysmon when performing emulations against a Windows system. The goal was to find out which tool was the least noisy. The different adversary emulation tools included in this thesis were Invoke-AtomicRedTeam, CALDERA, ATTPwn and Red Team Automation. To make sure the correlation between the adversary emulation tools and the generated event logs could be identified, a controlled experiment was selected as the method for the study. Five experiments were designed including one emulation scenario each, executed by the different adversary emulation tools included in each experiment. After each emulation, event logs were collected, filtered, and measured for use in the comparison. Three experiments were conducted which compared Invoke-AtomicRedTeam, CALDERA, and a manual emulation. The results of the first three experiments indicated that Invoke-AtomicRedTeam team was the noisiest, followed by CALDERA, and the manual emulation was the least noisy. On average, the manual emulation generated 83,9% fewer logs than Invoke-AtomicRedTeam and 78,4% fewer logs than CALDERA in experiments 1-3. A fourth experiment compared Red Team Automation and Invoke-AtomicRedTeam, where Red Team Automation was the least noisy tool. The final fifth experiment compared ATTPwn and CALDERA, and the results indicated that these were similarly noisy but in different ways. It was also concluded that a main difference between the adversary emulation tools was that the number of techniques available differed between the tools which could limit the ability to emulate the behavior of real adversaries. However, as the emulation tools were implemented in different ways, this thesis could be one starting point for future development of silent adversary emulation tools or to assist in selecting an existing adversary emulation tool.