A chemical ionisation mass spectrometer (CIMS) was developed and utilised for measurements onboard the Facility for Atmospheric Airborne Measurements (FAAM) BAe-146 aircraft. The I- ionisation scheme was implemented to detect nitric acid (HNO3), formic acid (HC(O)OH), hydrogen cyanide (HCN) and dinitrogen pentoxide (N2O5) simultaneously at a sampling frequency of 1 Hz. Sensitivities ranged from 35±6 ion counts pptv-1 s-1 for HC(O)OH to 4±0.9 ion counts pptv-1 s-1 for HCN and limits of detection from 37 ppt for HNO3 and 5 ppt for HCN. Trace gas concentrations of species such as HC(O)OH are currently under predicted in global models. In order to understand their role in controlling air quality, it is crucial that their production pathways and abundance are accurately measured and constrained. To date, airborne measurements of these trace gases have been difficult as a result of instrumental limitations on an aircraft such as limit of detection and sampling frequency. The first UK airborne measurements of HC(O)OH and HNO3 confirmed that HC(O)OH is under predicted by up to a factor of 2 in a trajectory model that implements the full Master Chemical Mechanism (MCM) and Common Representative Intermediate Scheme (CRI). The inclusion of a primary vehicle source enabled the model to reproduce the concentrations observed; verifying that direct sources are under represented. Secondary formation of HC(O)OH was observed through its correlation with HNO3 and ozone (O3), indicating a strong photochemical production source. Hydroxyl (OH) concentrations were estimated for the first time in a flight around the UK using the HC(O)OH and HNO3 measurements. A biomass burning (BB) plume identification technique is applied to data obtained from Canadian biomass fires using HCN as a marker. A 6 sigma above background approach to defining a plume resulted in a higher R2 correlating value for the normalised excess mixing ratio (NEMR) to carbon monoxide (CO) when compared to current methods in the literature. The NEMR obtained from this work; 3.76±0.02 pptv ppbv-1, lies within the range found in the literature. This NEMR is then used to calculate a global emission total for HCN of 0.92 Tg (N) yr-1 when incorporated into the global tropospheric model STOCHEM CRI. The first direct N2O5 airborne measurements on an aircraft at night are compared to indirect measurements taken by a broadband cavity enhancement absorption spectrometer. An average R2 correlation coefficient of 0.87 observed over 8 flights for 1 Hz measurements indicates the selectiveness of the I- ionisation scheme to detect N2O5 directly, without nitrate (NO3) interference.

This thesis studies the degradation of perovskite photovoltaic cells placed in atmospheres of different moisture. Samples with inverse structure: ITO/ PEDOT:PSS/ CH3NH3PbI3–XClX / PC70BM/ Ca/ Al were prepared. Electrical characteristics were measured for 2 months and similar degradation trend was observed for all the samples. Perovskite cell efficiency PCE decreased to 20 % of the initial value in t80= 46±3 days in laboratory, t80=23±1$ days in nitrogen atmosphere and t80=25,7±0,6 dní days in dry atmosphere. For the initial 27 days of the experiment, a faster degradation linked with the decrease of ISC, FF and VOC was observed. After this period, the value of FF has stabilised at 0,777±0,009 % and the value of VOC at 0,70±0,02 % of their original value (in the laboratory atmosphere). Additional fall of PCE resulted only from the decrease of ISC and was slower than in the initial period. From the results acquired, it has emerged that during the experiment, the cell encapsulation provided a sufficient barrier against outer moisture. Residual moisture present in the sctructure, was labeled as the source of the degradation. The moisture is believed to enter with the hygroscopic material PEDOT:PSS during the samples preparation procedure. During the degradation, absorption measurements of photovoltaic cells were executed. The absorption spectra didn't change. That indicates, that the decrease of ISC is not caused by the reduction of light absorption. The thesis also studied the degradation of perovskite solar cells under illumination. The samples were exposed to UV radiation for 55,5 hours. The PCE time of decrease to 20 % of the initial value was t80 = 6±2 days. It was revealed, that UV radiation significantly accelerates the decrease of ISC.

Adjacent cells communicate through gap junctions (GJs). These GJs are formed by head to head docking of two hemichannels (HCs) from two adjacent cells. HCs are connexin hexamer proteins. Connexin mutation is the most frequent cause of childhood hearing loss. This hearing impairment affects 2 in every 2000 children. Inhibition of the HCs might be the key factor to treat such disorders. A library of amphiphilic kanamycins was synthesized to be tested as HC inhibitors. These compounds showed excellent inhibition activity in comparison with the parent compound (kanamycin A) with less toxicity. A library of monosaccharide esters with varying carbon chain lengths (acetyl (C2) to hexadecyl (C16)) were synthesized, characterized, and tested for bioactivity. Carbohydrate esters showed low toxicity while remaining active against bacteria and fungi. The compound 6-O-tetradecanoyl-D-mannopyranose (MAN014), a mannose ester with a fourteen-carbon chain, showed the greatest antibacterial and antifungal properties. A mode of action study was tested against Staphylococcus aureus (bacteria) and Fusarium graminearum (fungus) and found the compound perturbed the cell membrum.

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Biological markers (i.e., biomarkers) are essential in clinical and epidemiological studies as they may provide mechanistic insights into the developmental origins of disease, as well as improve diagnostic testing and risk assessment for disease prevention. However, major challenges remain due to the lack of rapid yet selective analytical methods for high throughput screening that are also amenable to volume-restricted specimens. This thesis includes two major research themes that take advantage of capillary electrophoresis (CE) separations, including (1) the targeted analysis of urinary iodide and thiocyanate for assessment of nutritional adequacy and tobacco smoke exposures in the population, and (2) the discovery of new biomarkers in sweat specimens that may improve universal newborn screening programs for cystic fibrosis (CF) infants beyond impaired chloride transport. Chapter II examines the prevalence and risk factors associated with iodine deficiency in 24 h urine samples collected from 800 participants across four clinical sites in Canada as part of the Prospective Urban and Rural Epidemiological (PURE) study when using CE with UV detection in conjunction with sample self-stacking. Importantly, regional variations in iodine status were revealed with participants from Quebec City and Vancouver at greater risk for iodine deficiency than Hamilton and Ottawa. Overall, iodine supplement use, thyroxine prescription, urinary sodium excretion, and self-reported dairy intake were found to be protective factors against iodine deficiency. Chapter III applied a validated CE assay to measure urinary thiocyanate as a biomarker of tobacco smoke and dietary exposures in an international cohort of 1000 participants from the PURE study spanning 14 countries with varied income status, smoking habits, and diet quality. Current smokers residing in high-income countries had the highest extent of cyanide exposure indicative of greater harms from tobacco smoke compared to middle- and low-income countries after adjusting for smoking intensity and other covariates. Chapter IV introduces a rapid CE method with indirect UV detection to simultaneously measure sweat chloride and bicarbonate from presumptive CF infants’ residual sweat samples. Although bicarbonate did not provide clinical value in neonatal CF diagnosis, sweat chloride testing by CE may reduce test failure rates due to insufficient volumes from infants in a clinical setting. Lastly, Chapter V applied an untargeted strategy to characterize the sweat metabolome from presumptive CF infants when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). A panel of sweat metabolites were found to discriminate CF from non-CF (i.e., unaffected carriers) infants, including aspartic acid, glutamine, oxoproline, and pilocarpic acid, which also correlated with sweat chloride. The clinical utility of these sweat metabolites to prognosticate late-onset CF infants from indeterminate sweat chloride test results was also explored. In summary, this thesis contributes innovative separation methods for biomarker screening and discovery in clinical and epidemiological studies for the prevention and early treatment of human diseases that benefit from optimal nutrition. / Dissertation / Doctor of Philosophy (PhD)

Perovskit solceller (PSCs) är kända som 'ljusomvandling' enheter med ökad omvandlingseffektivitiet (PCE). PSCs är kända för detta flexibilitet och hög tolerans mot defekter och består av fem lager med olika material och egenskaper. De fem lagren är följande; transparant elektrod, elektron ledande lager (ETL), perovskit lager, hål ledande lager (HTL) och metallelektroden.  Detta forskningsarbete fokuserar på metallelektroden (Cu-tunn film), HTL (CuI-tunn film) och det aktiva lagret (CuI-komplex).  Syftet med denna studie är att undersöka effekten av olika tjocklekar på ytans morfologi och grovhet för att se mängden jod som tränger sig genom filmen genom att beräkna volymen.  Resultatet av denna studie visar att ökad tjocklek leder till ökad grovhet. Man ser även att en ökad tjocklek leder till ett mer homogent och jämn yta, och dessutom ökar kornstorleken, vilket tyder på att kvaliten av kristallisationen förbättras.  Slutligen, genom att känna till tjockleken och storleken (arean) på ytan av proverna kunde man beräkna volymen för att indikera mängden jod som trängt sig genom filmen. Resultatet av denna del indikerade att ju tjockare provet är, desto mer kommer jod att tränga sig genom filmen. / Perovskite solar cells (PSCs) are known as light-harvesting devices with increased power conversion efficiencies (PCE). PSCs are known for their flexibility and high tolerance towards defects. It consists of five different layers with different materials and functions. Transparent electrode, electron transport layer (ETL) , perovskite or active layer , hole transport layer (HTL) and metallic electrode. In this research project, the focus is directed towards the metallic electrode (Cu-thin film), hole transport layer (CuI-thin film) and the active layer (CuI-complex). The purpose of this study is to investigate the effect of different thicknesses on the surface morphology and roughness and to see how much iodine is diffusing through the film by calculating the volume.  The results of this project present that the increase in thickness leads to an increase in roughness. It also shows that an increase in thickness leads to a more homogeneous and uniform surface and in addition the grain size increases which indicates that the quality of crystallization improves. Finally, by knowing the thickness and surface area of the samples the volume was calculated to indicate how much iodine is diffusing through the film and the results for this part indicated that the thicker the sample, more iodine will diffuse through the film.

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Artemisia annua L. is a well-known medicinal herb used in Traditional Chinese Medicine for many centuries and contains artemisinin, which exhibits antimalarial properties [1] and is a potential treatment for SARS-CoV-2 [2]. However, the neurological effect of A. annua and its compounds are poorly understood. We hypothesize that A. annua extracts and artemisinin will provide protection against oxidative stress in mouse neuronal Neuro2A cells. Superoxide dismutase 1 (SOD1) is an anti-oxidant enzyme that protects against oxidative damage [3]. Growth Arrest and DNA Damage-inducible 45 alpha (Gadd45a) is involved in DNA repair and is a common biomarker for DNA damage[4]. SOD1 and Gadd45a mRNA expression was measured through RT-qPCR and analyzed using the 2-∆∆Ct method. Cell viability was measured using NucBlue, Annexin V, and propidium iodide to differentiate between apoptosis and necrosis. Cell counts were quantified using ImageJ (NIH). Our results showed that lower concentrations of 100 µg/mL A. annua treatment significantly reduced apoptotic cell death during oxidative stress. We also saw a general trend of decreasing Gadd45a mRNA expression at lower concentrations of A. annua treatment and a significant decrease in SOD1 mRNA levels from 0 to 100 µg/mL. This study suggests that lower concentrations of A. annua treatment prior to oxidative stress can increase cell viability and could protect Neuro2A cells from oxidative stress. Further research is needed to elucidate the mechanism of A. annua’s and artemisinin’s medicinal properties and further test their potential neuroprotective effects.

<p>This thesis presents novel approaches for structural investigation of glucuronides using chemical derivatization in combination with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MSⁿ).</p><p>Today, LC-ESI-MSⁿ is the dominant technique for quantitative as well as qualitative analyses of metabolites, due to its high sensitivity and selectivity. However, for compounds without an easily ionizable group, e.g., steroids, the sensitivity is limited. In the work presented in this thesis, a derivatization procedure forming a basic oxime significantly increased the detection sensitivity for the altrenogest glucuronide. </p><p>Furthermore, in structural evaluations of glucuronides, the limitation of LC-MSⁿ becomes evident due to the initial neutral loss of 176 u, i.e. monodehydrated glucuronic acid, which often makes it impossible to elucidate the structures of the conjugates. To solve this problem, the main part of the work described in this thesis was devoted to chemical derivatization as a means of facilitating the determination of the site of conjugation. </p><p>For the first time, the isomeric estriol glucuronides were evaluated using a combination of three reagents 2-chloro-1-methylpyridinium iodide (CMPI), 1-ethyl-3-(3-dimethyl- aminopropyl)-carbodiimide (EDC), and 2-picolylamine (PA). Interestingly, the derivatization gave a selective fragmentation pattern leading to differentiation of the isomers. </p><p>Another derivatization reagent, 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC), was also tested for the first time in structural investigations. The isomeric glucuronides of morphine, formoterol, and hydroxypropranolol were evaluated. They can all be conjugated in aliphatic as well as aromatic positions. DMISC was proven to be useful in two ways. Firstly, the morphine and formoterol glucuronides that contained a free phenol could be differentiated from those that were conjugated in the aromatic position based on different reactivity. Secondly, for the aromatic <i>O</i>-glucuronide of 4’-hydroxypropranolol, DMISC was proven to react with the amine. This product gave a different fragmentation pattern compared to the corresponding derivative of the aliphatic glucuronide. </p>