The analytical framework of enchanted objects has mainly been studied in the fields of anthropology and religion, but can equally be applied to fashion and dress. The aim of this thesis is to investigate the material process of enchantment through the fragments of count Carl Axel Lewenhaupt’s professional uniforms from fin de siècle Sweden. It further aims to uncover the myth(s) of noble masculinity by the theoretical perspectives of discipline and white masculinity. The thesis uses object analysis to dissect a Chamberlain uniform’s bicorn hat, a Hussar’s dolman jacket, and a Chamberlain court uniform (type B) and places them in assemblages of enchantment – the micro and macro settings that made the garments become powerful. Through the material splendour, elegance and sensory opulence of the garments, together with their placement in ceremonial, traditional, elevated and mythical environments, they could enchant nobility to symbolically remain dutiful, heroic and close to the King, even as noble power subsided. This thesis proposes a way in which dress may captivate senses even across the distance of history, and furthermore, exposes the process of material enchantment in the making of ideal and heroic masculinity, which is still relevant and alive in contemporary culture.

SOFIA (Studies On FIssion with Aladin) est un programme expérimental innovant qui a pour objectif la mesure de plusieurs observables de la fission nucléaire : les taux de production isotopiques des fragments de fission, l'énergie cinétique totale des fragments, et la multiplicité des neutrons prompts. Ces informations sont obtenues pour une large variété d'actinides et de pré-actinides. Le recours à la cinématique inverse (le système fissionnant est le faisceau et non pas la cible) est le seul moyen d'identifier les fragments à la fois en charge et en masse. Le travail de doctorat présenté dans cette thèse porte sur l'expérience menée en Octobre 2014 et dédiée à la mesure de la fission de ² ³ ⁶ U induite par excitation coulombienne, soit l'analogue de la fission de ² ³⁵U induite par neutron.Les expériences SOFIA ont lieu à GSI (Darmstadt, Allemagne), la seule installation au monde capable de délivrer un faisceau d'uranium ² ³⁸ de 1 GeV par nucléon. Ce faisceau primaire subit une première fragmentation, dont les produits sont sélectionnés par le FRS (FRagment Separator) afin de former un faisceau secondaire du noyau d'intérêt, en l'occurrence ² ³ ⁶ U, qui est guidé vers l'expérience SOFIA où sa fission est déclenchée.Certains noyaux proches de ² ³ ⁶ U sont également transmis par le FRS : il est donc nécessaire de procéder à l'identification en masse et en charge du système fissionnant, puis d'identifier les deux fragments de fission. Dans les deux cas, l'identification, réalisée événement par événement, repose sur la mesure simultanée de la perte d'énergie dans un gaz, de la rigidité magnétique et du temps de vol. Seules les fissions induites par excitation coulombiennes sont pertinentes : la contribution des réactions nucléaires à la production des fragments doit donc être mesurée et soustraite.L'analyse présentée dans ce document inclut l'identification du faisceau secondaire en masse et en charge, l'identification en charge des fragments de fission, l'estimation de la contribution des réactions nucléaires, et finalement les taux de production des éléments obtenus dans la fission de ² ³ ⁶ U. Ces résultats sont comparés à ceux d'autres mesures réalisées sur SOFIA, et à des résultats antérieurs obtenus par d'autres techniques. / SOFIA (Studies On FIssion with Aladin) is an innovative experimental program which aims to measure several fission observables — the isotopic fission yields, the total kinetic energy of the fragments and the prompt neutron multiplicity, for a wide range of actinides and pre-actinides. The use of inverse kinematics (the fissioning system is the beam instead of the target) is the only way to fully identify fragments in charge and mass. The PhD work presented in this thesis concerns the experiment conducted in October 2014, and is focused on the Coulomb-induced fission of ² ³ ⁶ U, which can be regarded as the analog of the neutron-induced fission of ² ³⁵U.The SOFIA experiments take place in GSI (Darmstadt, Germany) because it is the sole facility in the world which delivers a beam of ² ³⁸U at 1 AGeV. This beam is fragmented and the products are selected by the FRS (FRagment separator) in order to deliver a secondary beam of nuclei of interest - ² ³ ⁶ U in our case, which is then guided to the SOFIA setup where its fission is triggered.Since some nuclides with close atomic and mass numbers to ² ³ ⁶ U are also transmitted by the FRS, it is necessary to identify the fissioning system from the secondary beam first, and then identify both the associated fission fragments. All identifications are performed event by event on the basis of measurements of the energy loss, the magnetic rigidity and the time of flight. Since we are only interested in the Coulomb-induced fission of ² ³ ⁶ U, the contribution of fragmentation fissions on the nuclear charge distribution of fission fragments has to be suppressed.The analysis in this paper involves the isotopic identification of the fissioning system, the nuclear charge identification of the fission fragments, the estimation of the nuclear contribution, and the extraction of the elemental fission yield. The results are then compared to other measurements performed with the SOFIA setup, as well as previous results obtained by other techniques.

Les récepteurs couplés aux protéines G (RCPGs), constituent la plus grande famille de protéines membranaires dans le génome humain. Les RCPGs sont des protéines de signalisation, qui exercent leur action à la surface des cellules, en réponse à une grande variété de stimuli extérieurs. Ils jouent un rôle primordial dans de nombreuses fonctions physiologiques et sont donc impliqués dans une multitude de pathologies comme les maladies cardiovasculaires, métaboliques, neurodégénératives, psychiatriques et oncologiques. L'attribution du prix Nobel de chimie 2012 aux professeurs Robert Lefkowitz et Brian Kobilka pour leurs travaux et avancées spectaculaires dans le champ de recherches des RCPGs, souligne encore leur importance. Les RCPGs constituent également la plus importante cible thérapeutique, avec 30% des médicaments actuellement disponibles sur le marché qui exercent leur action via un RCPG. Cependant, la découverte de nouveaux ligands reste un chalenge. Le but est de développer des approches basées sur la RMN à l’état liquide, qui auront un impact positif sur la recherche de ligand de RCPGs, grâce à l’étude et la caractérisation de récepteur pleine taille, solubilisés en micelles de détergents ou enchâssés en bicouches lipidiques natives / G protein-coupled receptors (GPCRs) are the largest class of membrane proteins in the human genome. GPCRs act as cell surface signalling proteins and respond to a variety of external signals. They play a pivotal role in many physiological functions and are therefore associated with a multitude of diseases, including cardiovascular, metabolic, neurodegenerative, psychiatric, and oncologic diseases. The 2012 noble Prize in Chemistry was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka for studies of GPCRs, highlighting the importance of this protein superfamily. GPCRs constitute also the most important family of drug targets in the human body, with 30% of current drugs acting on GPCRs. However, drug discovery targeting GPCRs remains difficult, owing to the restricted structural information on GPCRs related to the instability of these proteins when isolated from their cell membrane environments. There is also a lack of knowledge for the structural and functional consequences of the interactions of small-molecule compounds with GPCR. The aim is to develop methods to study and characterize a full GPCR solubilized in detergents or in native lipid bilayers, both in its free form and in small molecule bound forms, using liquid-state NMR experiments. The aim is to develop NMR-based approaches that will strongly impact the structure-based drug discovery process for the GPCR family

This essay explores the magazine covers of Hemmets Journal between the years of 1921 and 1990. The first issue of the magazine was released one hundred years ago. The aim of the study is to examine how the motives have changed during the years in composition, color and text. The methods applied to this essay are formal analysis. Heinrich Wölfflin ́s set of five pairs of opposed visual concepts help distinguish when the clearest breakingpoints of the magazine covers occur. A style analysis is applied to the breakingpoints to examine if the contemporary structure of the society is depicted in the magazine covers. The results show for instance that you can spot the society in different ways in the magazine covers depending on what year it is and the most representative motive is women.

Crystallizing RNA has been an imperative facet and a challenging task in the world of RNA research. Assistive methods such as Chaperone Assisted RNA Crystallography (CARC), employing monoclonal antibody fragments (Fabs) as crystallization chaperones have enabled us to obtain RNA crystal structures by increasing the crystal contacts and providing initial phasing information. Using this technology the crystal structure of [delta]C209 P4-P6 RNA (an independent folding domain of the self-splicing Tetrahymena group I intron) complexed to Fab2 (high affinity binding Fab) has been resolved to 1.95 Å (1). Although the complexed class I ligase ribozyme has also been crystallized using CARC (2), in practice, it has been found that the crystallization of, large RNA-Fab complex remains a confrontation. The possible reason for this difficulty is that Fabs have not been optimized for crystallization when complexed with RNA. Here we have used the Surface Entropy Reduction technique (SER) for the optimization process. Candidate residues for mutations were identified based on combining results from visual inspection of [delta]C209 P4-P6/Fab2 crystal structure complex using pyMOL software and a web-based SER software. The protruding lysine and glutamate residues were mutated to a set of alanine (Super Mutant Alanine SMA) and serine (Super Mutant Serine SMS) mutant clones. Filter binding assay studies confirmed that the mutant clones bind to [delta]C209 P4-P6 with similar binding affinities as that of the parent Fab2. Large scale expression of the mutants, parent clone and [delta]C209 P4-P6 RNA were optimised. Crystal trays for [delta]C209 P4-P6 complexed with Fab2, Fab2SMA and Fab2SMS were set-up side-by-side using Hampton crystal screen kits and ~600 conditions including temperature as a variable condition were screened. Crystal screening shows significantly higher crystal-forming ratios for the mutant complexes. As the chosen SER residues are far away from the CDR regions of the Fab, the same set of mutations can be potentially applied to other Fabs binding to a variety of ribozymes and riboswitches to improve the crystallizability of the Fab-RNA complex.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

To address the unmet clinical need to eradicate treatment-resistant CD133+ cancer stems within tumors, a CSC-targeted radionuclide therapy (TRT) and companion diagnostic imaging probes were developed utilizing CD133-targeting antibodies and antibody fragments. In Chapter 1, background research providing context for the work in this Thesis is presented. In Chapter 2, a CD133-targeting antibody, RW03IgG, underwent radiolabeling with lutetium-177 to synthesize [177Lu]Lu-DOTA-RW03IgG for CD133-TRT. The CD133-TRT was evaluated for pharmacokinetics and treatment of a CD133 expressing human colorectal tumor bearing mouse model. Biodistribution studies on [177Lu]Lu-DOTA-RW03IgG demonstrated notable uptake in the colorectal tumors and off-target organ uptake consistent with previously reported antibody-based TRTs. Confirmation that tumor uptake was mediated by antibody-antigen binding was verified through co-injection with an excess dose of unlabeled RW03IgG. A dose-escalation therapy trial using [177Lu]Lu-DOTA-RW03IgG for treatment of the colorectal cancer mouse model revealed a dose-dependent reduction in tumor growth rate at well-tolerated doses. The decrease in tumor growth rate observed due to [177Lu]Lu-DOTA-RW03IgG treatment, along with an improvement in overall mouse survival, demonstrate the therapeutic efficacy of CD133-TRT. Additionally, histopathological and immunohistochemical (IHC) analyses indicated low off-target organ toxicity and significant anti-tumor effects. These findings suggested the potential for enhanced overall survival benefits through multiple doses. However, results on multiple-dosed CD133-TRT on the tumor growth rate and overall mouse survival were inconclusive. In Chapter 3, an orthotopic patient-derived glioblastoma (GBM) mouse model was developed that replicates anatomical pharmacokinetic challenges and CSC populations observed in patient tumors. Stereotactic engraftment of the patient GBM cells was optimized to reproducibly deliver tumor cells to the thalamus and growth was monitored using bioluminescence imaging. Ex vivo analysis confirmed various key characteristics of patient GBM, including CD133 expression, hypercellularity, and invasiveness. Biodistribution studies on [177Lu]Lu-DOTA-RW03IgG using the PDX GBM mouse model indicate antibody-antigen driven tumor uptake, determined through co-injection an excess dose of unlabeled RW03IgG. Ex vivo autoradiography supported the biodistribution results and showed elevated uptake of [177Lu]Lu-DOTA-RW03IgG in tumor relative to non-tumor bearing brain tissue. Chapters 4 and 5 centered on the development and evaluation of companion diagnostic CD133-targeted immunoPET probes. Chapter 4 specifically explored probes derived from the full antibody, RW03IgG. The probes were synthesized by conjugating RW03IgG with DFO-NCS to produce DFO-RW03IgG at different chelator-to-antibody ratios. The various DFO-RW03IgG conjugates were then radiolabeled with zirconium-89 to obtain [89Zr]-DFO-RW03IgG. Biodistribution studies and PET imaging revealed promising tumor uptake of [89Zr]-DFO-RW03IgG, and it was observed that higher chelator-to-antibody ratios led to increased accumulation in off-target organs. Chapter 5 investigated a probe derived from an scFv-Fc fragment of RW03, [89Zr]-DFO-RW03scFv-Fc. Biodistribution studies and PET images of colorectal tumor-bearing mice administered [89Zr]-DFO-RW03scFv-Fc showed favorable tumor uptake and low off-target organ accumulation. In Chapter 6, a probe for CD133-Photoacoustic Imaging (PAI) was synthesized through conjugation of RW03IgG with IR-783, an organic dye recognized for its favorable photoacoustic properties. Challenges were encountered in isolating the product, (IR-783)-RW03IgG, at high degrees of labeling (DOL) due to product aggregation. In vitro binding assays indicated that (IR-783)-RW03IgG (DOL = 1) maintained a comparable binding affinity to native RW03IgG. In vivo, colorectal tumors in mice administered (IR-783)-RW03IgG (DOL = 1) did not exhibit significant contrast from the background tissue, and the tumor PA signal did not differ significantly compared to tumors in mice administered an IR-783 labeled isotype IgG. The results suggest that a higher concentration of dye is needed within colorectal tumors for effective tumor visualization than what was provided by IR-783-RW03IgG. Chapter 7 investigated the use of Imaging Mass Cytometry (IMC) to simultaneously visualize [177Lu]Lu-DOTA-RW03IgG and multiple tumor biomarkers in tissue specimens collected from colorectal tumor xenograft mice treated with CD133-TRT. IMC showed undetectable concentrations of hafnium-177 (the decay product of lutetium-177) in tumors treated with CD133-TRT. However, lutetium-176 and lutetium-175, sourced from the carrier-added [177Lu]LuCl3 used in the synthesis of [177Lu]Lu-DOTA-RW03IgG, were present at levels sufficient for IMC visualization. The distribution of lutetium-176, representing [177Lu]Lu-DOTA-RW03IgG, within tumors, was imaged concomitantly with CD133, DNA damage markers, and several additional biomarkers that describe elements of the tumor microenvironment. These collective results endorse IMC as a useful tool to assess the distribution of TRT within tumors and uncover changes to the microenvironment in response to treatment. / Thesis / Doctor of Philosophy (PhD) / Targeted radionuclide therapy (TRT) and molecular imaging strategies were developed to aid in the elimination of the rare and particularly resilient Cancer Stem Cell (CSC) population in tumors. A fully human monoclonal antibody and antibody fragments targeting CD133, a molecular biomarker for CSCs, provided the means to deliver radioactive isotopes for therapy and imaging to CD133+ cells in tumors. The therapeutic efficacy of CD133-TRT for treatment of a colorectal cell line-derived xenograft mouse model was promising, and the treatment showed uptake in orthotopic patient derived glioblastoma tumors engrafted in mice. ImmunoPET probes targeting CD133 were optimized and successfully delineated CD133 expressing tumors from background tissue, warranting further evaluation using patient-representative cancer models. A non-invasive CD133-targeting Photoacoustic Imaging (PAI) probe was synthesized through conjugation of the CD133-targeting antibody to an organic dye, IR-783, although further probe optimization is required to provide tumor contrast. Tumor specimens from mice treated with CD133-TRT were assessed by Imaging Mass Cytometry (IMC), which revealed detectable concentrations of carrier isotopes from the therapy in the tumors, implicating the discovery of a powerful new tool for multiplexed single-cell level resolution imaging for cellular-scale analysis of targeted radionuclide therapy. The CSC-therapy and select molecular imaging probes generated in this Thesis warrant further evaluation using patient-representative mouse models of cancer.

By exploring the relationship between rituals and human behavior in relationship to architectural design the project "A Sense of Russia" searches for answers to new ways of sharing and experiencing culture over national boundaries, creating a stronger and clearer insight by physically engaging the visitor to be part of the other and the yet unknown. Using Russia and the program of the traditional Russian steam bath banya as a set framework, the project aims to address the subject through the implementation of one architectural incision. Questioning what place and shape a fragment of Russia would take in a non-Russian context like Sweden. By going through the different layers of human physical and mental interpretation, a patchwork of sorts, engaging in phenomenological and sociological ideas, this thesis explores how culture could be experienced through architectural design. Through the process of digging, casting and carving the project results in a proposal at the site of The Russian Yard located in Slussen, Stockholm. While unravelling the historical layers on site the proposal aims to offer new impressions and make the visitor behave in new patterns through unexpected scenarios. Trying to make Sweden see, hear, feel and maybe even make a little sense of Russia.

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