Thermomechanical recycling of polyethylene terephthalate (PET) typically includes a decrease in the polymer´s intrinsic viscosity and therefore a reduction of the molecular weight. Consequently, thermomechanical recycling is usually a downcycling of the product. However current methods to increase the molecular weight such as solid-state polymerization or the usage of chain extenders are time consuming or introduce foreign molecules into the PET´s molecular chain. Thus, the aim of this work was to try to increase the molecular weight in the molten state in an extruder, to decrease the processing times. The processing times are reduced compared to the solid-state polymerization because in the molten state the movability of the polymer chain is increased. Moreover, no supplementary substances are added for the processing so that no foreign structures are introduced during reprocessing. Virgin PET pellets were extruded at 285°C, 290°C and 295°C set temperature and 2rpm, 4rpm, and 7rpm screw rotation rate. Afterwards the PET´s properties were investigated by measuring their intrinsic viscosities, conducting a 1H NMR and a DSC measurement. Additionally, pre-experiments were conducted to explore the possibilities of feeding industrial scrap polyester fabrics into the extruder. The polymer characterization showed that the intrinsic viscosity and therefore the molecular weight of the processed samples decreased with the parameters chosen for this experiment. Samples processed at 285°C and 7 rpm showed in the average the highest intrinsic viscosities and therefore the highest molecular weight of all processed samples. Additionally, the results of the 1H NMR and the DSC indicated degradation reactions such as thermal degradation and hydrolysis. Thus, further research is necessary to find an easily accessible recycling method for polyester textiles and reduce the amount of polyester textile waste. However, it is possible to feed long textile stripes into the twin screw extruder and reprocess it to a strand which is an important step for further recycling.

Ce travail de thèse est consacré à l'étude en imagerie multimodale des bases neurobiologiques des pathologies psychiatriques, avec un intérêt particulier pour les voies dopaminergiques et le système de récompense. Son principal objectif est d'établir, par l’intermédiaire de la Tomographie à Emission de Positons (TEP) et l’Imagerie par Résonance Magnétique (IRM), un lien entre le système dopaminergique et le système de récompense d’un point de vue fonctionnel et structurel chez l’Homme, et en particulier chez des patients présentant des troubles psychiatriques tels que la schizophrénie, l’addiction à la cocaïne et la dépression. De nombreuses études ont démontré l’existence concomitante d’anomalies de la fonction dopaminergique et du système de récompense dans plusieurs troubles mentaux. Cependant, la connaissance des liens entre dysfonctions dopaminergiques et dysfonctions du circuit de la récompense dans les pathologies psychiatriques reste limitée. L’objectif de cette thèse est ainsi d’améliorer les connaissances sur la physiopathologie de plusieurs troubles mentaux comme la schizophrénie, l’addiction et la dépression, et de démontrer l’intérêt d’une approche dimensionnelle et de l’utilisation de l’imagerie multimodale pour l’exploration du niveau moléculaire de réseaux neuronaux fonctionnels dans la recherche en psychiatrie. En perspective, ce travail de thèse soutient l’intérêt de l’imagerie en pratique psychiatrique, car elle pourrait par la suite permettre de préciser le diagnostic, prédire les réponses aux traitements ou étudier l’évolution de la maladie au cours du temps. / This work focuses on the study of the neurobiological bases of psychiatric disorders using multimodal imaging, with a particular interest in the dopaminergic pathways and the reward system. Its primary objective is to establish, through Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), a link between the dopaminergic system and the reward system from a functional and structural point of view in humans, and especially in patients with psychiatric disorders such as schizophrenia, cocaine addiction and depression. Numerous studies have demonstrated the concomitant existence of abnormalities affecting dopaminergic function and reward system in several mental disorders. However, understanding of the linkages between dopaminergic dysfunction and dysfunction of the reward circuit in psychiatric disorders remains limited. The main aims of this thesis are to improve knowledge about the pathophysiology of several mental disorders such as schizophrenia, addiction and depression, and to demonstrate the interest of both a dimensional approach and the use of multimodal imaging in psychiatric research, to explore the molecular level of functional neural networks. In perspective, this thesis supports the interest of brain imaging in clinical practice, as it could later clarify the diagnosis, predict response to treatments or follow the course of the disease.

Bakgrund: Sveriges befolkning blir allt äldre. Det är en stor heterogen grupp i behov av vårdinsatser och ett antal äldre bor idag på särskilda boenden. Det är vanligt förekommande med fysisk och psykisk ohälsa, ensamhet samt bristande social interaktion på särskilda boenden för äldre. Det har tidigare visats att införandet av hundar inom vården kan minska fysisk och psykisk ohälsa samt öka motivation till deltagande i fysioterapi. Syfte: Undersöka och sammanställa vad vetenskaplig littereratur visar angående fysiska, psykiska och sociala hälsoeffekter hos äldre på särskilda boenden vid regelbunden interaktion med vårdhund. Metod: Litteratursökningen genomfördes via databasen PubMed och åtta vetenskapliga artiklar inkluderades. Artiklarna granskades via PEDro-skalan i syfte att skatta studiekvaliteten. Evidensstyrkan betygsattes sedan via SBU:s metod GRADE. Resultat: Begränsad evidens har visat sig för effektmåtten depression, apati, ångest, aggression, livskvalité, emotioner och ensamhet. Det har visat sig att djurassisterad terapi med hund har otillräckligt vetenskapligt underlag för effektmåtten energiåtgång, fysisk aktivitet, ADL, vikt, BMI, kognition och social interaktion. Konklusion: Resultatet från denna litteraturstudie visar varierande evidens för djurassisterad terapi med hund. Studien påvisar att djurassisterad terapi med hund kan ha positiv effekt på vissa effektmått hos äldre personer på särskilda boenden. Evidensen är som starkast för psykiska effektmått. Vidare forskning med större väl genomförda studier är relevant för att fortsatt kunna utvärdera effekterna av djurassisterad terapi med hund. / Background: The population of Sweden is getting older. It is a big and heterogeneous group in need of health care and a number of older people are living in a nursing home. It is common with physical and mental disorders, loneliness and lack of social interaction in nursing homes. It is shown that animal assisted therapy with dogs can reduce physical and mental illness and motivate older people to participate in physiotherapy. Objective: Examine and compile evidence of animal assisted therapy with dogs on physical, mental och social function in elderly living in a nursing home. Methods: The search was done in the PubMed database and eight articles became included. The articles were assessed for study quality confirmed by the PEDro scale. The evidence from the articles were assessed confirmed by the SBU GRADE. Results: Limited evidence was shown for that animal asssisted therapy with dogs can improve symptoms of depression, apathy, anxiety, agitation, quality of life, emotions and loneliness. Insufficent evidence was found for energy expenditure, physical activity, ADL, weight, BMI, cognition and social interaction. Conclusions: Results show varying evidence for animal assisted therapy with dogs. This study shows that animal assisted therapy with dogs can improve some limited effects in the population of older people at nursing homes, especially for mental health effects. More well made research with larger groups is indicated to ensure and value these effects.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18853号 / 医博第3964号 / 新制||医||1007(附属図書館) / 31804 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 泰広, 教授 武田 俊一, 教授 野田 亮 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20252号 / 医博第4211号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 三森 経世, 教授 伊達 洋至, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20984号 / 医博第4330号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 森田 智視, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Interior walls are one of the biggest environmental culprits in office renovations. With this project I want to consider a new way to radically alter the layout of public spaces without producing waste.  The purpose of this project is to investigate the potential for using brickwork as an inspiration for adaptable walls in offices and public spaces. I will explore how sustainable, lightweight materials such as hemp or wool can be used to create lightweight “bricks” with acoustic properties. These bricks are assembled in an accordion-like structure that allows the wall to be extended, folded and to create various shapes.  By rethinking the interior wall, I have created a circular system of semi-permanent walls that can transform offices, workspaces and meeting rooms at will, and allows for an affordable and sustainable alternative to costly and disruptive renovations. With a leasing system the walls are part of a circular business model. Using brickwork as an inspiration, and a way to connect innovations to architectural history, this project explores the possibilities inherent in the modularity of bricks.

College football stadiums host anywhere from 15,000 to 115,000 people each Saturday from late summer to early winter and leave fans exposed to ambient conditions. Amplified heat from stadium infrastructure substantially impact attendants’ thermal comfort. In order to assess personal heat exposure and mitigate exposure misclassification, temperature and relative humidity sensors (iButtons) were placed throughout Mississippi State University’s Davis Wade Stadium during the 2016 Football Season. iButton measurements established a micro-climate and compared its readings to the Soil Climate Analysis Network site 1.2 miles north of the stadium. The program RayMan Pro modeled a Physiological Equivalent Temperature (PET) micro-climate to create an individualized heat metric. The results of this study assess stadium occupants’ thermal comfort through Heat Index and PET. Heat-related health outcomes were examined regarding thermal comfort and the stadium micro-climate using data from the stadium’s EMS calls and First Aid stations during game days.

PET imaging is a key tool in the fight against cancer. One of the main issues of PET imaging is the high level of noise that characterizes the reconstructed image, during this project we implemented several algorithms with the aim of improving the reconstruction of PET images exploiting the power of Neural Networks. First, we developed a simple denoiser that improves the quality of an image that has already been reconstructed with a reconstruction algorithm like the Maximum Likelihood Expectation Maximization. Then we implemented two Neural Network based iterative reconstruction algorithms that reconstruct directly an image starting from the measured data rearranged into sinograms, thus removing the dependence of the reconstruction result from the initial reconstruction needed by the denoiser. Finally, we used the most promising approach, among the developed ones, to reconstruct images from data acquired with the KTH MTH microCT - miniPET.

Recently discovered methods for both diagnosis and treatment management of heart failure (HF) and other cardiovascular diseases include the use of molecular imaging modalities such as positron emission tomography (PET). As such, PET radiotracers have been developed and show strong evidence for quantifiable sympathetic nervous system (SNS) imaging in animals and humans using radioligands that target the norepinephrine transporter (NET). In this study, the cardiac sympathetic nervous system imaging probe [¹⁸F]meta-fluorobenzylguanidine ([¹⁸F]mFBG) was evaluated in Sprague Dawley (SD) rats and hypothesized to i) have measurable NET-dependent uptake kinetics; ii) possess measurable NET reuptake, iii) be stored into vesicles, and remain metabolically stable within the myocardium, iv) be sensitive to changes in sympathetic tone, and v) discriminate between healthy and diseased animals. Using the selective NET inhibitor desipramine (DMI) and nonselective extraneural and neural uptake inhibitor phenoxybenzamine (PBZ) we observed 30-35% and ~70% reduced uptake in the myocardium, respectively. Neuronal ablation with 6-hydroxydopamine (6-OHDA) resulted in a 36% loss of myocardial retention. DMI and PBZ chase dosing revealed no change in myocardial washout by PET, suggesting minimal reuptake of the tracer and preferential clearance into blood. Pretreatment with the vesicular monoamine transporter (VMAT) inhibitor reserpine (RSP) reduced myocardial retention by 34% within 5 minutes in comparison to baseline, providing evidence for intraneural vesicular retention. Dahl salt-sensitive (DSS) rats were induced with HF via high salt (HS, 8%) diet. After 16 weeks, rats kept on HS diet showed ~32% reduced myocardial uptake in comparison to low salt (LS) controls. Non-invasive PET imaging of HF is therefore sensitive to the expected changes in myocardial uptake in small animal imaging. The myocardial cholinergic system was evaluated using the vesicular acetylcholine transporter (VAChT) ligand [¹⁸F]fluoroethoxybenzylvesamicol ([¹⁸F]FEOBV) in CD-1 mice. We hypothesized that i) [¹⁸F]FEOBV uptake in the myocardium is VAChT dependent; and more specific in the absence of isoflurane anesthesia. Baseline uptake was observed in the ventricles. However, pretreatment with vesamicol in the presence and absence of isoflurane did not reduce myocardial activity. Analysis of PET images in mice with differential cardiac VAChT expression showed minimal changes in blood and cardiac activity. These studies have demonstrated a lack of specific binding of [¹⁸F]FEOBV in the myocardium of mice, rendering this imaging probe unfit in interpreting cholinergic function in small animals. The second half of the thesis is focused on the development of a radiolabeling technique using novel iminophosphorane precursors, and their subsequent reactivity and application using the naturally abundant (99% carbon-12) and positron emission tomography (PET) imaging isotope (carbon-11). We hypothesized that the reaction of iminophosphorane precursors with [¹¹C]CO₂ with allow us to i) synthesize a myriad of labelled isocyanate derived functional groups ii) apply this chemistry to label relevant radiopharmaceuticals in high yield and molar activity. Optimization of reaction conditions was performed, and a substrate scope was developed. Using the naturally abundant carbon isotope, we synthesized isocyanate derived functional groups such as carbamates, thiocarbamates, ureas, and amides in 63-94% yield. Pharmaceuticals such as regorafenib, URB694, and melatonin were synthesized in 60-72% yield. When applied to carbon-11 radiochemistry, labelled products were produced in 32-84% radiochemical yield (RCY). Radiopharmaceuticals such as [¹¹C]URB694 and [¹¹C]glibenclamide were synthesized in high yield and molar activity suitable for preclinical evaluation. We have demonstrated the utility of iminophosphorane precursors in synthesizing labelled functional groups and relevant radiopharmaceuticals in high yields, enabling their use for future preclinical or clinical studies. The recent development of the potent and selective nod-like receptor protein-3 (NLRP3) inhibitor MCC950 has demonstrated remarkable application as a therapeutic in reducing macrophage infiltration and aortic lesion area, but has yet to be applied to PET imaging due to poor synthesis yields. We hypothesized that i) using our previously established iminophosphorane chemistry we can synthesize [¹¹C]MCC950, and ii) selective uptake of [¹¹C]MCC950 occurs in aortic atherosclerotic lesions. We successfully radiolabeled [¹¹C]MCC950 in 45 ± 4 % RCY (27 ± 2 GBq/µmol). Plasma metabolite analysis revealed 94% intact tracer after 15 minutes, and ex vivo autoradiography on excised aortas showed heterogeneous uptake in atherosclerotic plaques of ApoE⁻ᐟ⁻ mice. Pretreatment with nonradioactive MCC950 resulted in significantly increased uptake in aortic lesions (48 ± 17 %ID/m² vs 104 ± 15 %ID/m²), without significantly increasing plasma free fraction (1.3 ± 0.4% vs 1.7 ± 0.8%). The data suggests increased specific binding following blockade which may be due to biochemical mechanisms such as disaggregation of NLRP3 oligomers, artificially increasing the available number of binding sites. Thus, the data suggest [¹¹C]MCC950 uptake demonstrates specific binding and may therefore prove useful as an in vivo imaging probe to detect NLRP3-mediated inflammation in atherosclerosis.