Differential cross section measurement of top quark pair production with the CMS experiment using a ML-based kinematic reconstruction

openIn this thesis a measurement of the differential cross section of top quark pair production in proton-proton (pp) collisions at a center-of-mass energy of 13 TeV is presented. The measurement is performed with data collected in 2018 using the Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC), corresponding to an integrated luminosity of 59.83 fb-1. The analysis is performed using the dileptonic different-flavor e-mu decay channel. The cross section is measured differentially as a function of the invariant mass of the top quark pair system. The presence of two final state neutrinos makes a kinematic reconstruction necessary for the measurement of m(ttbar). In this work, the observable m(ttbar) is regressed from the visible detector objects by a neural network, leading to an improvement in the efficiency, resolution and a reduction of the statistical uncertainties in the unfolded cross section compared to results based on analytical reconstruction approaches.In this thesis a measurement of the differential cross section of top quark pair production in proton-proton (pp) collisions at a center-of-mass energy of 13 TeV is presented. The measurement is performed with data collected in 2018 using the Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC), corresponding to an integrated luminosity of 59.83 fb-1. The analysis is performed using the dileptonic different-flavor e-mu decay channel. The cross section is measured differentially as a function of the invariant mass of the top quark pair system. The presence of two final state neutrinos makes a kinematic reconstruction necessary for the measurement of m(ttbar). In this work, the observable m(ttbar) is regressed from the visible detector objects by a neural network, leading to an improvement in the efficiency, resolution and a reduction of the statistical uncertainties in the unfolded cross section compared to results based on analytical reconstruction approaches

Deciphering the transcriptional states of Müller glia and their progeny in the regenerating zebrafish retina

The retina is the neural tissue situated at the back of the eyes that samples the visual scene and sends the processed information to the brain. Millions of people worldwide suffer from retinal diseases that affect mainly the light sensing photoreceptors or retinal ganglion cells, the output neurons projecting to the brain. Despite promising attempts in the fields of gene therapy and cell transplantation, a definitive cure for retinal diseases is still missing. Research on highly regenerative organisms like zebrafish (Danio rerio) offers an attractive perspective to inform gene as well as cell transplantation-based therapies to treat retinal pathologies. Indeed, the zebrafish retina has the same structure and function as the human retina, including the presence of all retinal neurons as well as Müller glia, glial cells that provide structural and metabolic support. Remarkably, and differently from mammalian species, zebrafish Müller glia behave additionally as stem cells upon tissue damage. In this context, Müller glia re-enter the cell cycle and generate retinal progenitors that eventually differentiate to all retinal neurons. In the last twenty years, there has been a considerable effort to understand the molecular mechanisms underlying zebrafish Müller glia reprogramming to pro-regenerative stem cells and retinal progenitor production. However, a comprehensive study of the molecular identity of Müller glia, Müller glia-derived retinal progenitors as well as regenerated progeny in uninjured and lesioned conditions is still missing. Furthermore, although retinal progenitors regenerate all retinal neurons, independently of the specific retinal cell type that has been mostly affected by the tissue damage, it is not known whether all regenerated progeny integrate and rewire into the existing circuitry. The present study had two aims: • First, it aimed to provide a comprehensive description of Müller glia, Müller glia-derived progenitors as well as regenerated progeny in uninjured and light-lesioned retina at 44 hours as well as at 4 and 6 days post-lesion. • Second, it aimed to establish a CreERT2 recombinase-based strategy to allow genetic access to follow and manipulate Müller glia-derived progenitors and their progeny during regeneration. To achieve the first aim, a short-term lineage tracing strategy was devised using the two fluorescent reporters Tg(gfap:mCherry) and Tg(pcna:EGFP) labelling Müller glia and proliferating cells, respectively. Double transgenic animals were employed to sort for Müller glia, Müller glia-derived progenitors as well as regenerated progeny from the uninjured and light-lesioned retina. Subsequently, 10x Genomics, single cell RNA sequencing was performed to characterize their transcriptome and to deduct their differentiation trajectories during retina regeneration. The sequencing experiment showed the presence of a glial and a neurogenic trajectory in the regenerating retina up to 6 days post-lesion. The glial trajectory starts with non-reactive Müller glia, characterized by canonical glial markers, and continues with injury-reactive Müller glia at 44 hours post-lesion, which upregulate genes associated with glia reprogramming and inflammation as well as proliferation. These early reactive Müller glia divide and generate cells belonging to a population with a hybrid identity that becomes eminent at 4 days post-lesion and is characterized by marker genes of both Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. While the glial self-renewal trajectory feeds back to the non-reactive Müller glia cell population, the neurogenic trajectory continues with neurogenic progenitors, which progressively express markers of restricted fate competence and eventually regenerate several retinal neurons. The birthdate order of the regenerated progeny recapitulates the order observed during retinal development to a great extent. Indeed, retinal ganglion cells and red cone photoreceptors are born at 4 days post-lesion, followed by blue cones, amacrine and bipolar cells at 6 day post-lesion. Regenerated rod photoreceptors as well as horizontal cells were not detected among the sorted progeny, despite detection of their committed precursors. To achieve the second aim, genetic access to Müller glia-derived cells was established using the TgBAC(mmp9:CreETt2,cryaa:EGFP);Tg(Olactb:loxP-DsRed2-loxP-EGFP) double transgenic line. The injury-induced promoter mmp9 is expressed in reactive Müller glia and drives the expression of CreERT2. Upon administration of the metabolite 4-hydroxytamoxifen, CreERT2 catalyses recombination in the Cre-dependent reporter Tg(Olactb:loxP-DsRed2-loxP-EGFP), resulting in the expression of EGFP under the control of the broadly expressed Olactb promoter. Subsequently, recombined cells, which include progenitors and progeny, express EGFP permanently. Two time points of 4-hydroxytamoxifen intraperitoneal injection were tested to achieve efficient recombination: 6 hours post-lesion, corresponding to 2 hours prior to onset of mmp9 in reactive Müller glia, and 24 hours post-lesion. In both cases, a substantial number of EGFP-positive, Müller glia-derived cells was observed in the regenerating retina at 4 days post-lesion. The majority of the EGFP-positive cells co-localized with PCNA-positive nuclei and corresponded most likely to progenitors. Importantly, EGFP-positive cells were neither observed in the light-lesioned, ethanol injected controls nor in the uninjured, 4-hydroxytamoxifen-injected controls, indicating tight control of CreERT2. In conclusion, the current PhD thesis provides a comprehensive description of the transcriptome of Müller glia, Müller glia-derived retinal progenitors and regenerated progeny. Moreover, it establishes a CreERT2-based approach to study the composition as well as long-term integration of Müller glia-derived cells in the regenerated retina and allow their genetic manipulations in future studies

Bolling v. Sharpe and Beyond: The Unfinished and Untold History of School Desegregation in Washington, D.C.

While the Brown V. Board of Education case is constantly referenced when discussing educational equity and desegregation, Bolling v. Sharpe stands as another important education civil rights case and is perhaps more telling of the story of education in the United States. Bolling V. Sharpe was argued and decided in the United States Supreme Court over the course of 1952 to 1954. Similar to Brown v. Board in terms of intent, Bolling v. Sharpe aimed to desegregate public schools in Washington, D.C. in order to give African-American students equal access to a high quality public education on par with that of their white peers. This historical study will examine the factors that led to the case of Bolling v. Sharpe, analyze the cases intended impact and discuss the factors that led to its ultimate failure. Bolling v. Sharpe intended to end segregation for African-American students in D.C. public schools, and the larger African- American and civil rights communities perceived the verdict as a victory. However, the court ruling itself could not undo decades of systemic racism, and could not account for the de facto segregation that Washington, D.C. would endure over the course of twenty years in relation to social and economic policies. Despite civil rights leader’s best efforts, de facto segregation replaced de jure segregation, and the cities African-American student population still lagged behind their white peers academically and socially. Socio-economic conditions and the historical context of race in D.C. has stifled the academic achievement of African-American students in Washington D.C, leaving a much more complicated legacy of Bolling v. Sharpe than many would like to acknowledge

Quantitative strain analysis of the large deformation at the scale of microstructure: comparison between Digital Image Correlation and Microgrid techniques

A comparative study has been carried out to assess the accuracy of the Digital Image Correlation (DIC) technique for the quantification of large strains in the microstructure of an Interstitial Free (IF) steel used in automotive applications. A microgrid technique has been used in this study in order to validate independently the strain measurements obtained with DIC. Microgrids with a pitch of 5 microns were printed on the etched microstructure of the IF steel to measure the local in-plane strain distribution during a tensile test carried out in a Scanning Electron Microscope (SEM). The progressive deformation of the microstructure with microgrids has been recorded throughout the test as a sequence of micrographs and subsequently processed using DIC to quantify the distribution of local strain values. Strain maps obtained with the two techniques have been compared in order to assess the accuracy of the DIC measurements obtained using the natural patterns of the revealed microstructure in the SEM micrographs. The results obtained with the two techniques are qualitatively similar and thus, demonstrate the reliability of DIC applied to microstructures, even after large deformations in excess of 0.7. However, an average error of about 16 % was found in the strain values calculated using DIC

Droits des robots

Durante décadas, hemos estado usando, teniendo, administrando refrigeradores, automóviles y teléfonos móviles. En suma, máquinas. Sin embargo, nadie ha pensado, hasta ahora, que tales má- quinas podrían ser titulares de derechos. Las máquinas hasta ahora han sido “objetos” de derechos (propiedad, posesión, responsabilidad) y ciertamente no “sujetos”. ¿Cómo es esto? Por la sencilla razón de que solo recientemente estas máquinas han comenzado a tener formas propias de inteligencia artificial que empiezan a hacer dudar de que puedan asumir una cierta autonomía decisional. ¿Entonces estas máquinas pueden ser titulares de situaciones jurídicas propias? Los robots de hace cien años no eran más que un invento literario de Karel Capek. Un invento fascinante para el desarrollo inmediato que los robots han tenido en la literatura de ciencia ficción de los siguientes años.Hasta el punto que un visionario como Asimov consiguiera establecer las leyes de la robótica. Era 1942. Pero hoy estamos realmente a punto de tener que escribir estas leyes. No solo porque están cambiando profundamente los derechos de las personas humanas, sino también porque están empezando a configurarse derechos propios de las máquinas.For decades, we have been using, managing refrigerators, automobiles and mobile phones. In short, machines. However, no one has thought, until now, that such machines could be rights holders. Machines so far have been “objects” of rights (ownership, possession, responsibility) and certainly not “subjects” of right. How is this? For the simple reason that only recently these machines have begun to have their own forms of artificial intelligence that begin to make it doubtful that they can assume a certain decision-making autonomy. Can be these machines the holders of their own legal situations? The robots of a hundred years ago were nothing more than a literary invention of Karel Capek. A fascinating invention for the immediate development that robots have had in the science fiction literature of the following years. To the extent that a visionary like Asimov managed to establish the laws of robotics. It was 1942. But today we are really about to have to write these laws. Not only because the rights of human beings are profoundly changing, but also because the rights of machines are beginning to take shape.Durante décadas, temos estado usado, tendo, administando refrigeradores, carros e telefones celulares. Em suma, máquinas. No entanto, ninguém pensou, até agora, que essas máquinas poderiam ser titulares de direitos. As máquinas até agora têm sido “objetos” de direitos (propriedade, possessão, responsabilidade) e certamente não “sujeitos”. Como é isso? Pela simples razão de que só recentemente essas máquinas começaram a ter formas próprias de inteligência artificial que começam a fazer duvidar de que podem assumir certa autonomia de decisão. Então, essas máquinas podem ser titulares de situações legais próprias? Os robôs de cem anos atrás não eram mais que uma invenção literária de Karel Capek. Uma invenção fascinante para o desenvolvimento imediato que os robôs tiveram na literatura de ficção científica dos anos seguintes. A tal ponto que um visionário como Asimov conseguiu estabelecer as leis da robótica. Era 1942. Mas hoje estamos realmente a ponto de ter que escrever essas leis. Não só porque estão mudando profundamente os direitos das pessoas humanas, mas também porque estão começando a configurar-se direitos próprios das máquinas.Pendant des décennies, nous avons utilisé, possédé et géré réfrigérateurs, voitures et téléphones portables. En bref, des machines. Cependant, personne n’a pensé jusqu’à présent que de telles machines pourraient bénéficier de droits. Les machines étaient jusqu’à présent des “objets” de droits (propriété, possession, responsabilité) et certainement pas des “sujets”. Et pourquoi donc? Pour la simple raison que ce n’est que récemment que ces machines ont commencé à être dotées d’une forme propre d’intelligence artificielle; il pourrait en découler qu’elles puissent assumer une certaine autonomie décisionnelle. Donc, ces machines peuvent-elles être titulaires de situations juridiques propres? Les robots d’il y a cent ans n’étaient rien de plus qu’une invention littéraire de Karel Capek. Une invention fascinante vu le développement immédiat que les robots ont eu dans la littérature de science-fiction des années suivantes. Au point qu’un visionnaire comme Asimov a réussi à établir les lois de la robotique. C’était en 1942. Mais aujourd’hui, nous sommes vraiment sur le point de devoir écrire ces lois. Non seulement parce les droits des personnes humaines connaissent un profond changement, mais aussi parce que les machines commencent à bénéficier de droits propres.Facultad de Ciencias Jurídicas y Sociale

Calcium-Activated Potassium Channels Inhibition in Autonomically Stimulated Human Atrial Myocytes

The autonomic nervous system has been reported to play a major role in the generation and maintenance of atrial fibrillation. Various investigations have suggested small-conductance calcium-activated potassium (SK) channels as potential targets for more effective pharmacological therapies. In this study, we used in silico modeling and simulation to investigate the effects of SK channel inhibition on the action potential (AP) of autonomically stimulated human atrial cardiomyocytes. The Grandi AP model, with a new formulation for the ISK current, was used to represent human atrial electrophysiology. Choliner-gic stimulation by different concentrations of acetylcholine (ACh) hyperpolarized the AP and shortened the AP duration (APD) in a dose-dependent manner, with up to 7 mV resting membrane potential elevation and >200 ms APD shortening for 1 µM ACh at 1 Hz pacing frequency. Additional ß-adrenergic stimulation by 1 µM Isoproterenol (Iso) partially attenuated the effects of cholinergic stimulation by prolonging the APD by 41.6%. ISK inhibition was able to reverse the effects of cholinergic activation, but only for moderate ACh doses and when combined with 1 µM Iso, leading to 58.3% prolongation of the AP stimulated with 0.01 µM ACh. In conclusion, ISK inhibition combined with ß-adrenergic stimulation can be effective in antagonizing cholinergic effects on human atrial myocytes

Strain Evolution Measurement at the Microscale of a Dual Phase Steel Using Digital Image Correlation

Digital Image Correlation (DIC) together with in-situ tensile testing has been used to measure in DP1000 steel the evolution of plastic strains at the microstructure scale. Interrupted tensile tests were performed on specially designed samples and scanning-electron micrographs were taken at regular applied strain intervals. Patterns defined by the microstructural features of the material have been used for the correlation carried out using LAVision software. The full field strain maps produced by DIC show a progressive localisation of deformation into bands at about 45o with respect to the loading direction. Plastic strains as high as 130% have been measured within the ferrite phase

Albert Camus et la démocratie comme alternative aux totalitarismes du xxe siècle

Cet article propose une lecture de la création de Camus sous l’angle démocratique et antitotalitaire pour démontrer l’aspect innovant de sa pensée qui est plus que jamais d’actualité. Après avoir tracé le portrait de l’auteur en tant que journaliste engagé, nous passerons à une analyse comparée entre Camus et les intellectuels qui ont influencé sa pensée démocratique et qui ont inspiré ses idées sur le totalitarisme. Ensuite, nous focaliserons l’analyse sur certaines œuvres afin d’examiner la technique adoptée par Camus pour transférer dans la fiction le débat démocratique contre les totalitarismes de son époque. Enfin, nous étudierons du point de vue lexicologique les termes de totalitarisme et démocratie, ainsi que tous leurs synonymes entrant dans le champ sémantique du débat antitotalitaire.This article proposes a (re)reading of Camus creation from the perspective of the democracy in order to demonstrate the innovative aspect of his thought, which is more actual than ever. After outlining a portrait of the author as a committed journalist, we will proceed to a comparative analysis between Camus and intellectuals who influences his democratic thought and inspired his thinking on totalitarianism. Then, based on a selection of works, we will examine the technique adopted by Camus to transfer into the fictional the democratic debate against totalitarianism of his era. Finally, we will study from a lexicological point of view the terms of totalitarianism and democracy, and their synonyms within the semantic field of the antitotalitarian debate

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Hyperactivity of the parasympathetic nervous system has been linked to the development of paroxysmal atrial fibrillation (AF). The parasympathetic neurotransmitter acetylcholine (ACh) causes a reduction in action potential (AP) duration (APD) and an increase in resting membrane potential (RMP), both of which contribute to enhance the risk for reentry. Research suggests that small-conductance calcium activated potassium (SK) channels may be an effective target for treating AF. Therapies targeting the autonomic nervous system, either alone or in combination with other drugs, have been explored and have been shown to decrease the incidence of atrial arrhythmias. This study uses computational modeling and simulation to examine the impact of SK channel block (SKb) and β-adrenergic stimulation through Isoproterenol (Iso) on countering the negative effects of cholinergic activity in human atrial cell and 2D tissue models. The steady-state effects of Iso and/or SKb on AP shape, APD at 90% repolarization (APD90) and RMP were evaluated. The ability to terminate stable rotational activity in cholinergically-stimulated 2D tissue models of AF was also investigated. A range of SKb and Iso application kinetics, which reflect varying drug binding rates, were taken into consideration. The results showed that SKb alone prolonged APD90 and was able to stop sustained rotors in the presence of ACh concentrations up to 0.01 μM. Iso terminated rotors under all tested ACh concentrations, but resulted in highly-variable steady-state outcomes depending on baseline AP morphology. Importantly, the combination of SKb and Iso resulted in greater APD90 prolongation and showed promising anti-arrhythmic potential by stopping stable rotors and preventing re-inducibility