The plasma environment of an active comet provides a unique setting for plasma physics research. The complex interaction of newly created cometary ions with the flowing plasma of the solar wind gives rise to a plethora of plasma physics phenomena, that can be studied over a large range of activity levels as the distance to the sun, and hence the influx of solar energy, varies. In this thesis, we have used measurements of the spacecraft potential by the Rosetta Langmuir probe instrument (LAP) to study the evolution of activity of comet 67P/Churyumov-Gerasimenko as it approached the sun from 3.6 AU in August 2014 to 2.1 AU in March 2015. The measurements are validated by cross-calibration to a fully independent measurement by an electrostatic analyzer, the Ion Composition Analyzer (ICA), also on board Rosetta. The spacecraft was found to be predominantly negatively charged during the time covered by our investigation, driven so by a rather high electron temperature of ~5 eV resulting from the low collision rate between electrons and the tenuous neutral gas. The spacecraft potential exhibited a clear covariation with the neutral density as measured by the ROSINA Comet Pressure Sensor (COPS) on board Rosetta. As the spacecraft potential depends on plasma density and electron temperature, this shows that the neutral gas and the plasma are closely coupled. The neutral density and negative spacecraft potential were higher in the northern hemisphere, which experienced summer conditions during the investigated period due to the nucleus spin axis being tilted toward the sun. In this hemisphere, we found a clear variation of spacecraft potential with comet longitude, exactly as seen for the neutral gas, with coincident peaks in neutral density and spacecraft potential magnitude roughly every 6 h, when sunlit parts of the neck region of the bi- lobed nucleus were in view of the spacecraft. The plasma density was estimated to have increased during the investigated time period by a factor of 8-12 in the northern hemisphere and possibly as much as a factor of 20-44 in the southern hemisphere, due to the combined effects of seasonal changes and decreasing heliocentric distance. The spacecraft potential measurements obtained by LAP generally exhibited good correlation with the estimates from ICA, confirming the accuracy of both of these instruments for measurements of the spacecraft potential.

abstract: The physiological phenomenon of sensing temperature is detected by transient receptor (TRP) ion channels, which are pore forming proteins that reside in the membrane bilayer. The cold and hot sensing TRP channels named TRPV1 and TRPM8 respectively, can be modulated by diverse stimuli and are finely tuned by proteins and lipids. PIRT (phosphoinositide interacting regulator of TRP channels) is a small membrane protein that modifies TRPV1 responses to heat and TRPM8 responses to cold. In this dissertation, the first direct measurements between PIRT and TRPM8 are quantified with nuclear magnetic resonance and microscale thermophoresis. Using Rosetta computational biology, TRPM8 is modeled with a regulatory, and functionally essential, lipid named PIP2. Furthermore, a PIRT ligand screen identified several novel small molecular binders for PIRT as well a protein named calmodulin. The ligand screening results implicate PIRT in diverse physiological functions. Additionally, sparse NMR data and state of the art Rosetta protocols were used to experimentally guide PIRT structure predictions. Finally, the mechanism of thermosensing from the evolutionarily conserved sensing domain of TRPV1 was investigated using NMR. The body of work presented herein advances the understanding of thermosensing and TRP channel function with TRP channel regulatory implications for PIRT. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2018

Cette thèse s'inscrit dans le cadre de l'expérience de spectrométrie de masse d'ions secondaires à temps de vol, COSIMA, se trouvant à bord de la mission européenne cométaire Rosetta. Cet instrument a pour vocation de collecter puis de mesurer la nature chimique des grains de la comète 67P/Churyumov-Gerasimenko. L'objectif de ma thèse est de préparer et de faciliter l'interprétation des spectres de masse de COSIMA, et plus particulièrement de leur composante organique réfractaire. Pour cela, à partir d'un instrument de laboratoire conçu spécialement pour présenter des caractéristiques instrumentales similaires à COSIMA, les spectres de masse de deux familles de composés purs (hétérocycles azotés et acides carboxyliques) ont été mesurés. Ces données ont été qualifiées en tant que spectres de masse de référence utilisables par l'équipe COSIMA. Cette base de données est le point de départ de la recherche de marqueurs permettant la distinction des molécules constituées d'atomes particuliers. Deux marqueurs ont été trouvés. Néanmoins ils sont à manipuler avec prudence compte tenu des biais pouvant être induits par la présence de minéraux au sein des grains ou de contaminants sur les cibles d'analyse. L'analyse d'analogues de la matière organique cométaire a également été effectuée. Il en ressort que les mesures réalisées avec COSIMA peuvent présenter des biais importants. L'identification des polymères de HCN en est d'ailleurs compromise. Toutefois, l'analyse d'un grain de la météorite de Murchison montre que la distinction entre les composantes minérale et organique est facilement réalisable. De plus, les signatures de composés clés comme l'hexaméthylènetétramine ou le polyoxyméthylène (POM) sont clairement identifiables dans le mode positif de l'instrument. Le POM étant thermiquement instable, une étude cinétique de sa dégradation thermique a été réalisée en vue de contraindre la stratégie opérationnelle à adopter pour sa détection. Pour maximiser les chances de le détecter dans les grains cométaires, les analyses par COSIMA doivent être effectuées dans les quinze jours après la collecte des grains.

Two variants of ancient Egyptian were used for different categories of written communication during the last millennium B.C. The vernacular, known as Demotic, served as the written language for administrative, legal and literary documents. Traditional Egyptian (égyptien de tradition), written in the hieroglyphic script and with linguistic structures that are purported to imitate those of the Classical Egyptian, was still used to compose mainly religious documents. The present work treats the verbal system of Traditional Egyptian using texts dated to the period 400-30 B.C. These documents include royal stelae and priestly decrees, among these the Rosetta Stone, as well as biographical inscriptions. After a general introduction, and a presentation of morphological characteristics, the study takes up the basic verbal patterns. The suffix conjugations, the sDm=fand sDm.n=f , in its various meanings and combinations, affirmative and negative, are dealt with, as is the pseudoparticiple. The infinitive, as it appears in e.g. pseudoverbal constructions and the sDm pw ir.n=f is examined in a separate section, with an additional chapter covering the passive forms of the suffix conjugation. A summary of the conclusions that are reached by this study are presented in the final chapter. Graphic variations show that morphemes formerly used to distinguish verbal classes are largely ignored. Only a few irregular verbs still display, at times, writings that retain the old inflections, often, however, without corresponding to the category that would be expected given the context. These writings are unevenly distributed among the documents, testifying to the existence of local, or perhaps rather individual, grammatical systems. Similarly, the co-existence in Traditional Egyptian of the two forms of the suffix conjugation sDm.n=fand sDm=f, both used to express a completed event, is best understood when each document is studied separately. There is a general avoidance of forms and expressions that parallel those found in Demotic. This appears to have been of greater importance than following the rules of Classical Egyptian. The use of the conjunctive and infinitival constructions, under certain conditions, confirms this observation.

L'étude des noyaux cométaires est primordiale pour comprendre la formation et l'évolution du système solaire. Cette thèse présente plusieurs méthodes et modèles pour déterminer leurs propriétés physiques (rayon, albédo géométrique, inertie thermique et fraction de surface active) à partir des observations visibles, infrarouges et des mesures de taux de production de l'eau, et pour quantifier l'activité à leur surface. Nous étudions le noyau des comètes Hale-Bopp (C/1995 O1), 55P/Tempel-Tuttle, 126P/IRAS, 103P/Hartley 2, 22P/Kopff, 46P/Wirtanen, IRAS-Araki-Alcock (C/1983 H1) et 2P/Encke, celui des Centaures Chiron (2060) et Chariklo (1997 CU26) et celui des comètes rasantes. De cette étude, il ressort que: (i) l'albédo géométrique des Centaures vaut 0.07-0.11 et est supérieur à celui des LPC (comètes à longue période) et des SPC (comètes à courte période) qui vaut 0.04-0.07, (ii) un albédo faible n'est pas incompatible avec la présence de glace d'eau en surface, (iii) l'inertie thermique du noyau est faible et vaut <3 J/K/m2/s1/2, (iv) la distance du périhélie, combinée à la sublimation de la glace d'eau, n'est pas un argument suffisant pour expliquer la différence de rayon entre les comètes rasantes (<0.11 km), les SPC (0.6-2.4 km), les LPC (3-38 km) et les Centaures (71-118 km), (v) la formation d'une croûte sur les SPC est très probable et peut expliquer les variations du taux de production de l'eau avec la distance héliocentrique, et (vi) l'activité à la surface des noyaux cométaires n'est pas nécessairement confinée à quelques régions actives; les SPC de petite taille (~1 km) ont une activité répartie sur toute leur surface. Les zones actives localisées, associées à la présence de jets dans la coma, existent seulement sur une minorité d'objets, les plus gros.

The development of hybridoma technology nearly forty years ago set the foundation for the use of antibodies in the life sciences. Subsequent advances in recombinant DNA technology have allowed us to adapt antibody genes to various screening systems, greatly increasing the throughput and specialized applications for which these complex biomolecules can be adapted. While selection systems are a powerful tool for discovery and evolution, they can be slow and prone to unintended biases. We see computational approaches as an efficient process for rapid discovery and engineering of antibodies. This is particularly relevant for biodefense and emerging infectious disease applications, for which time is a valuable commodity. In the first chapter of this work, we examine computational protocols for ‘supercharging’ proteins. This process resurfaces the target protein, adding charged moieties to impart specialized functions such as thermoresistance and cell penetration. Current algorithms for resurfacing proteins are static, treating each mutation as an event within a vacuum. The net result is that while several variants can be created, each must be tested experimentally to ensure the resultant protein is functional. In many cases, the designed proteins were severely impaired or incapable of folding. We hypothesize that a more dynamic approach, keeping an eye on energetics and the consequences of mutations will yield a more efficient and robust method for supercharging, successfully adding charges to proteins while minimizing deleterious effects. We continue on this theme applying the successful algorithm to supercharging antibodies for increased function. Utilizing the MS2 model biosensor system, we rationally engineer charges onto the surface of an antibody fragment, increasing thermoresistance, minimizing destabilizing effects, and in some cases actually increasing affinity. Finally, we apply next-generation sequencing approaches to the rapid discovery of antibodies directed against the Zaire Ebolavirus species. We utilize a local immunization strategy to generate a polarized antibody repertoire that is then sequenced to provide a database of antigen-specific variants. This repertoire is probed in silico and individual antibodies selected for analysis, bypassing time- and resource-consuming selection experiments. / text

Comets are the most active around their perigees. The increased outgassing can lead to a coma thick enough to effectively absorb the solar EUV radiation, which engenders a self-shielding comet nucleus and inner layers of the ionosphere. This effect of self-shielding can be calculated by the attenuation of the sunlight according to the Beer-Lambert law. Here we focus on the perihelion of comet 67P/Churyumov-Gerasimenko, the target comet of the ESA Rosetta mission. We calculate attenuated photoionization frequencies and implement these into an ionospheric model constructed in a recent project work (by the same author). The ionization frequencies and ion number densities are calculated as a function of cometocentric distance and compared with the latest published peer-reviewed article by Heritier et al. (2017). Overall, the agreement is fairly good. The most significant difference is the discrepancy of number densities of O2 ions, which is higher in our model by nearly an order of magnitude. This discrepancy is attributed to the fact that Heritier et al (2017) only considered charge transfer processes for the formation of O2+, while we identify photoionization of O2 as the main production mechanism.

No description available.

The plasma environment of an active comet provides a unique setting for plasma physics research. The complex interaction of newly created cometary ions with the flowing plasma of the solar wind gives rise to a plethora of plasma physics phenomena, that can be studied over a large range of activity levels as the distance to the sun, and hence the influx of solar energy, varies. In this thesis, we have used measurements of the spacecraft potential by the Rosetta Langmuir probe instrument (LAP) to study the evolution of activity of comet 67P/Churyumov-Gerasimenko as it approached the sun from 3.6 AU in August 2014 to 2.1 AU in March 2015. The measurements are validated by cross-calibration to a fully independent measurement by an electrostatic analyzer, the Ion Composition Analyzer (ICA), also on board Rosetta. The spacecraft was found to be predominantly negatively charged during the time covered by our investigation, driven so by a rather high electron temperature of ~5 eV resulting from the low collision rate between electrons and the tenuous neutral gas. The spacecraft potential exhibited a clear covariation with the neutral density as measured by the ROSINA Comet Pressure Sensor (COPS) on board Rosetta. As the spacecraft potential depends on plasma density and electron temperature, this shows that the neutral gas and the plasma are closely coupled. The neutral density and negative spacecraft potential were higher in the northern hemisphere, which experienced summer conditions during the investigated period due to the nucleus spin axis being tilted toward the sun. In this hemisphere, we found a clear variation of spacecraft potential with comet longitude, exactly as seen for the neutral gas, with coincident peaks in neutral density and spacecraft potential magnitude roughly every 6 h, when sunlit parts of the neck region of the bi- lobed nucleus were in view of the spacecraft. The plasma density was estimated to have increased during the investigated time period by a factor of 8-12 in the northern hemisphere and possibly as much as a factor of 20-44 in the southern hemisphere, due to the combined effects of seasonal changes and decreasing heliocentric distance. The spacecraft potential measurements obtained by LAP generally exhibited good correlation with the estimates from ICA, confirming the accuracy of both of these instruments for measurements of the spacecraft potential. / <p>QC 20200602</p>

No description available.