L'objectif principal de cette thèse est l’étude spectroscopique de molécules ou de complexes portant plusieurs centres chiraux en phase gazeuse, pour comprendre les effets de la stéréochimie sur leurs propriétés structurales. Des alcaloïdes dérivés de la Cinchonine ont été introduits intacts en phase gazeuse par ablation laser. Ils ont été étudiés en combinant un jet supersonique avec de la spectroscopie laser. Les deux pseudo-énantiomères Quinine et Quinidine ont montré des spectres électroniques et vibrationnels similaires, en accord avec leur structure similaire. Leurs propriétés en solution diffèrent davantage, comme le montrent les expériences de dichroïsme circulaire vibrationnel (VCD). Cette différence est encore plus marquée dans l’Hydroquinine et l’Hydroquinidine. Enfin la reconnaissance chirale a été étudiée dans des complexes ioniques dans un piège à ions. La stabilité des complexes formés entre S-camphre et les R et S-Alanine protonées indique une préférence homochirale. Cependant, l'énergie d'interaction calculée ainsi que les spectres IRMPD dans la région des empreintes digitales sont identiques. Le rôle des conformères plus hauts en énergie dans la reconnaissance chirale a été discuté. / The main objective of this thesis is a spectroscopic study of molecules or complexes bearing multiple chiral centres in the gas phase, to understand the effects of stereochemistry on their structural properties. Neutral cinchona alkaloids have been introduced intact in gas phase by laser-ablation. They have been studied by combining supersonic expansion with laser spectroscopy. The two pseudo-enantiomers Quinine and Quinidine show similar electronic and vibrational spectra, in line with similar structure. Their properties in solution differ more, as shown by Vibrational Circular Dichroism (VCD) experiments. This difference is further enhanced in Hydroquinine and Hydroquinidine. Lastly chiral recognition has been studied in ionic complexes in an ion trap. A homochiral preference has been shown in the stability of the complexes formed between S-Camphor and R and S protonated Alanine. However, the calculated interaction energy as well as the IRMPD spectrum in the fingerprint region are identical. The role of higher energy conformers in chiral recognition has been discussed.

Samhällsdigitaliseringen har lett till att byggbranschen mer och mer strävar efter att digitalisera verktyg och arbetssätt. Att presentera projekt i 3D har därför blivit ett hett ämne där flera aktörer strävar efter att både projektera och nyttja 3D ute i produktionen. Tidigare forskning inom ämnet har till största del valt att lägga fokus på byggskedet och belyser de fördelar som går att utvinna genom nyttjandet av så kallade VDC- eller BIM verktyg. Samtidigt belyser andra vetenskapliga rapporter mark och anläggning som ett betydelsefullt skede inom hela byggprocessen. Ett flertal menar också att mark- och anläggningsskedet spelar en huvudroll i huruvida ett byggprojekt når framgång eller inte. Med detta i åtanke upplever författarna att 3D-modeller i mark- och anläggningsprojekt inte utforskats till den grad som känns nödvändig för att belysa fördelarna, men även de olika hinder som står i vägen för en lyckad implementeringsprocess. Det råder inte heller några tvivel om att byggskedet kommit längre i digitala utvecklingsaspekter, så som att visualisera projekt i 3D, vid en jämförelse med mark och anläggning. I denna studie belyser därför författarna de fördelar som går att utvinna genom att visualisera mark- och anläggningsprojekt i 3D. Studien visar upp bevis på varför verktyget bör implementeras och vad aktörer bör tänka på vid en eventuell implementering av 3Dvisualisering i projekt. Syftet med studien är därav att utreda hur det undersökta fallföretaget kan integrera 3D-modeller i mark- och anläggningsprojekt, samt belysa vilka krav fallföretagets anställda ställer på en 3D-modell för att främja utvecklingen av ett verktyg som passar och leder till en hög nyttjandegrad ute i produktionen. Vidare sker en identifiering av vilka förutsättningar ute i mark och anläggningsprojekt som spelar en nyckelroll i huruvida en implementerad 3D-modell skall kunna figurera och verka så som det är tänkt. Studien utförs med en kvalitativ metod där granskning av befintlig litteratur lyfter fram de problemområden som författarna identifierat. Vidare utförs semistrukturerade intervjuer med tjänstemän och yrkesarbetare på fallföretaget Veidekke Entreprenad AB. Intervjuerna genomförs i syfte att identifiera aktuella problem ute i produktionen, undersöka respondenternas syn på 3D-modeller samt belysa verktygets potentiella inverkan på deras vardagliga arbete.  En tydligt övergripande slutsats är att 3D-modeller i allra högsta grad behövs ute i produktionen på mark- och anläggningsprojekt. Mycket pekar på att verktyget bland annat skulle bidra med en ökad förståelse kring utförandet av projekten, men också förbättra kommunikation och produktionsledande. Verktyget kan också enligt studien minimera problemområden gällande tekniska lösningar, förbättra planering, samt genom att digitalisera moment även tillfredsställa arbetsglädjen för produktionsteamet. / Due to the digitalization the construction business is increasingly striving against more digitized tools and working methods. Presenting projects in 3D has therefore become a hot topic where several actors are trying to implement 3D not only in the design phase but also in the production phase. Earlier research dealing with the subject largely chooses to focus on the building construction process and highlights the advantages that can be extracted using so called VDC- or BIM tools. Some of the scientific reports reviewed during this study on the other hand, highlights the importance of the infrastructure and earthworks stages as a part of the entire construction process. Many also believe that the infrastructure and earthworks stage play a key role in whether a construction project achieve success or not. With that in mind, the authors feel that 3D-models for infrastructure and earthworks, have not yet been explored to the extent that feels necessary, meaning that the advantages and the various obstacles that stand in the way of a successful implementation process needs to be investigated. There is no doubt that building construction has come further in a digital development aspect of visualizing projects in 3D, compared to infrastructure and earthworks. In this study the authors have highlighted the benefits that can be gained by visualizing infrastructure and earthworks projects in 3D. The study also shows evidence of why the application of such should take place and what companies should be considering when implementing 3D visualization into such projects. The purpose of the study is therefore to investigate how the company researched by the authors can integrate 3D models into their infrastructure and earthworks projects. This in addition to identifying the requirements that the employees have on a 3D model to facilitate development of a tool that fulfils these requirements and is usable in production. In addition, the conditions and requirements that play a main role in infrastructure and earthworks projects have been investigated to identify the most suitable conditions to allow the model to work in the most efficient way as possible. The study is conducted with a qualitative method including an examination of existing literature that highlights the problem areas identified by the authors. In addition, semi structured interviews are carried out with employees from the work-site leadership and the skilled workers at the company Veidekke Entreprenad AB. This to identify the current problem areas in the production of infrastructure and earthworks projects and to examine employees’ view about how 3D models would impact on their everyday work. A clear overall conclusion is that 3D-models are truly needed in infrastructure and earthworks projects out in production. A lot of factors indicate that the tool would, among other things, contribute to an increased understanding of the scope of projects and thus contribute to an improved communication and production process leading. Such a tool can according to this study, also minimize problem areas regarding technical solutions, contribute to a better planning, and by digitizing processes, increase job satisfaction for the site team.

L'objectif principal de cette thèse est l'étude spectroscopique de molécules ou de complexes portant plusieurs centres chiraux en phase gazeuse, pour comprendre les effets de la stéréochimie sur leurs propriétés structurales. Des alcaloïdes dérivés de la Cinchonine ont été introduits intacts en phase gazeuse par ablation laser. Ils ont été étudiés en combinant un jet supersonique avec de la spectroscopie laser. Les deux pseudo-énantiomères Quinine et Quinidine ont montré des spectres électroniques et vibrationnels similaires, en accord avec leur structure similaire. Leurs propriétés en solution diffèrent davantage, comme le montrent les expériences de dichroïsme circulaire vibrationnel (VCD). Cette différence est encore plus marquée dans l'Hydroquinine et l'Hydroquinidine. Enfin la reconnaissance chirale a été étudiée dans des complexes ioniques dans un piège à ions. La stabilité des complexes formés entre S-camphre et les R et S-Alanine protonées indique une préférence homochirale. Cependant, l'énergie d'interaction calculée ainsi que les spectres IRMPD dans la région des empreintes digitales sont identiques. Le rôle des conformères plus hauts en énergie dans la reconnaissance chirale a été discuté.

Ovarian cancer is thought to be derived from the ovarian surface epithelium (OSE), but it is often diagnosed during the late stages and therefore the events that contribute to the initiation and progression of ovarian cancer are poorly defined. Epidemiological studies have indicated an association between the female reproductive hormones and ovarian cancer etiology, but the direct effects of 17β-estradiol (E2), progesterone (P4), luteinizing hormone (LH) and follicle stimulating hormone (FSH) on disease pathophysiology are not well understood. A novel transgenic mouse model of ovarian cancer was generated that utilized the Cre/loxP system to inducibly express the oncogene SV40 large and small T-Antigen in the OSE. The tgCAG-LS-TAg mice developed poorly differentiated ovarian tumours with metastasis and ascites throughout the peritoneal space. Although P4 had no effect; E2 significantly accelerated disease progression in tgCAG-LS-TAg mice. The early onset of ovarian cancer was likely mediated by E2’s ability to increase the areas of putative preneoplastic lesions in the OSE. E2 also significantly decreased survival time in ovarian cancer cell xenografts. Microarray analysis of the tumours revealed that E2 mainly affects genes involved in angiogenesis and cellular differentiation, proliferation, and migration. These results suggest that E2 acts on the tumour microenvironment in addition to its direct effects on OSE and ovarian cancer cells. In order to examine the role of the gonadotropins in ovarian cancer progression, the tgCAG-LS-TAg mice were treated with 4-vinylcyclohexene-diepoxide (VCD) to induce menopause. Menopause slowed the progression of ovarian cancer due to a change in the histological subtype from poorly differentiated tumours to Sertoli tumours. Using a transgenic mouse model, it was shown that E2 accelerated ovarian cancer progression, while P4 had little effect on the disease. Menopause (elevated levels of LH and FSH) altered the histological subtype of the ovarian tumours in the tgCAG-LS-TAg mouse model. These results emphasize the importance of generating animal models to accurately recapitulate human disease and utilizing these models to develop novel prevention and treatment strategies for women with ovarian cancer.

Ovarian cancer is thought to be derived from the ovarian surface epithelium (OSE), but it is often diagnosed during the late stages and therefore the events that contribute to the initiation and progression of ovarian cancer are poorly defined. Epidemiological studies have indicated an association between the female reproductive hormones and ovarian cancer etiology, but the direct effects of 17β-estradiol (E2), progesterone (P4), luteinizing hormone (LH) and follicle stimulating hormone (FSH) on disease pathophysiology are not well understood. A novel transgenic mouse model of ovarian cancer was generated that utilized the Cre/loxP system to inducibly express the oncogene SV40 large and small T-Antigen in the OSE. The tgCAG-LS-TAg mice developed poorly differentiated ovarian tumours with metastasis and ascites throughout the peritoneal space. Although P4 had no effect; E2 significantly accelerated disease progression in tgCAG-LS-TAg mice. The early onset of ovarian cancer was likely mediated by E2’s ability to increase the areas of putative preneoplastic lesions in the OSE. E2 also significantly decreased survival time in ovarian cancer cell xenografts. Microarray analysis of the tumours revealed that E2 mainly affects genes involved in angiogenesis and cellular differentiation, proliferation, and migration. These results suggest that E2 acts on the tumour microenvironment in addition to its direct effects on OSE and ovarian cancer cells. In order to examine the role of the gonadotropins in ovarian cancer progression, the tgCAG-LS-TAg mice were treated with 4-vinylcyclohexene-diepoxide (VCD) to induce menopause. Menopause slowed the progression of ovarian cancer due to a change in the histological subtype from poorly differentiated tumours to Sertoli tumours. Using a transgenic mouse model, it was shown that E2 accelerated ovarian cancer progression, while P4 had little effect on the disease. Menopause (elevated levels of LH and FSH) altered the histological subtype of the ovarian tumours in the tgCAG-LS-TAg mouse model. These results emphasize the importance of generating animal models to accurately recapitulate human disease and utilizing these models to develop novel prevention and treatment strategies for women with ovarian cancer.

Ovarian cancer is thought to be derived from the ovarian surface epithelium (OSE), but it is often diagnosed during the late stages and therefore the events that contribute to the initiation and progression of ovarian cancer are poorly defined. Epidemiological studies have indicated an association between the female reproductive hormones and ovarian cancer etiology, but the direct effects of 17β-estradiol (E2), progesterone (P4), luteinizing hormone (LH) and follicle stimulating hormone (FSH) on disease pathophysiology are not well understood. A novel transgenic mouse model of ovarian cancer was generated that utilized the Cre/loxP system to inducibly express the oncogene SV40 large and small T-Antigen in the OSE. The tgCAG-LS-TAg mice developed poorly differentiated ovarian tumours with metastasis and ascites throughout the peritoneal space. Although P4 had no effect; E2 significantly accelerated disease progression in tgCAG-LS-TAg mice. The early onset of ovarian cancer was likely mediated by E2’s ability to increase the areas of putative preneoplastic lesions in the OSE. E2 also significantly decreased survival time in ovarian cancer cell xenografts. Microarray analysis of the tumours revealed that E2 mainly affects genes involved in angiogenesis and cellular differentiation, proliferation, and migration. These results suggest that E2 acts on the tumour microenvironment in addition to its direct effects on OSE and ovarian cancer cells. In order to examine the role of the gonadotropins in ovarian cancer progression, the tgCAG-LS-TAg mice were treated with 4-vinylcyclohexene-diepoxide (VCD) to induce menopause. Menopause slowed the progression of ovarian cancer due to a change in the histological subtype from poorly differentiated tumours to Sertoli tumours. Using a transgenic mouse model, it was shown that E2 accelerated ovarian cancer progression, while P4 had little effect on the disease. Menopause (elevated levels of LH and FSH) altered the histological subtype of the ovarian tumours in the tgCAG-LS-TAg mouse model. These results emphasize the importance of generating animal models to accurately recapitulate human disease and utilizing these models to develop novel prevention and treatment strategies for women with ovarian cancer.

Determinar la configuración absoluta de las moléculas quirales representa un gran reto para los químicos orgánicos. Para conseguir este objetivo existen diversas técnicas, las cuales se describen en el presente trabajo, así como ejemplos de cómo han sido utilizadas para la determinación de la configuración absoluta de productos naturales. / Methods for the assignment of the absolute configuration of an organic molecule: The assignment of the absolute configuration of chiral molecules represents a great challenge for organic chemists. There are several techniques in order to establish it, and they are described in this work, as well as examples of how they can be applied in the assignment of the absolute configuration of natural products.