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A cation-responsive electrode system has been developed which incorporates aza-substituted crown ethers as ligands. In a novel application, uncomplexed crown ethers were used in the pelletized form for ionic transport. Electrodes have been produced which can be conditioned for a particular ion and following their use, be reconditioned and reused for other ions. Preparation method and lifetime studies are included. The responses of two crown ethers with plasticizers were evaluated for thirteen representative cations. The concentration range covered in each evaluation was 1 x 10-1 to 1 x 10-7 M. For those ions exhibiting Nernstian or near-Nernstian response, selectivity coefficients were derived.

The selective catalytic reduction by ammonia (NH3-SCR) of nitrogen oxides (NOx) is a promising technology that is applied to eliminate NOx pollutants from combustion sources like diesel engines. Mn-based oxides are considered a promising catalyst for this process and many efforts were exerted by scholars to make improvements, including addition of other elements to the catalyst framework. The present study investigates the reaction mechanism and pathways using in-situ DRIFTS FTIR analysis for three Mn-based catalysts: a) mixed metal oxide MnCeTiOx, b) Mn impregnated on mesoporous titanium silicate-1 Mn/MesoTS1, and c) Mn/MesoTS1 after protection by secondary growth of silicalite-1 abbreviated as SG-Mn/MesoTS1. Various experiments were carried out on all the catalysts involving pre adsorbing NH3 then introducing NO+O2 to react with the pre adsorbed species and vice versa. It was found that the mixed metal oxide, MnCeTiOx, exhibited higher activity due to variation of different metals and higher metal content compared to the Mn-zeolite catalysts, approximately 29 Wt% Mn vs 4 Wt %, respectively. However, from comparing the two Mn-zeolite catalysts, each containing roughly 5 Wt% Mn, the catalyst after protection by secondary growth, SG-Mn/MesoTS1, showed improvement in the adsorption capability enhancing the overall performance due to the higher amount of acid sites than Mn/MesoTS1, explained by the presence of additional Brønsted and Lewis acid sites. From DRIFTS experiments, both E-R and L-H mechanism could be coexisting and taking place at 150C for all three catalysts. However, it was concluded that although both mechanisms could take place during the reaction, the acid sites on the catalyst surface for all three samples mostly favor the adsorption of NH3 species over NOx species making the E-R mechanism more assertive at 150C.

The mixing and evaporation of Diesel Exhaust Fluid (DEF) inside an Urea Selective Catalyst Reduction (SCR) chamber has been numerically investigated. The first task in this work has been to first look into the numerical framework and assess the models available in a commercial CFD software (ANSYS Fluent 14.5). Secondly the knowledge inherited from the model sensitivity analysis will be applied on the practical case of an Urea-SCR mixing chamber. Mass flow rate and temperature effects of the exhaust gas on the mixing and evaporation of the DEF spray has been investigated. The results indicate that evaporation rates inside the mixing chamber are dependent on the mass flow rate of the exhaust gas but not on the temperature due to compressibility effects of the exhaust gas. For a constant mass flow rate an increase in temperature decreases the residence time of droplets (due to compressibility) with a similar order of magnitude as the individual droplet evaporation rate increases (due to higher temperature) thus the two effects balances each other. The results could potentially contribute to the development and optimization of current SCR systems.

In this study, we explore two factors of selective exposure and their effect on the relation between political sympathies and xenophobic attitudes in Sweden. Previous studies implies that internet and social media-platforms, as well as political interest, are two important factors behind selective news consumption in todays fragmented media landscape. Based on previous studies we hypothesised that; news consumption via social media/internet and political interest effects the relation between political sympathies and xenophobia, and that the effect is positive if the individual sympathies with Sweden democrats and negative if the sympathies lie with the Left party. The result shows that among all Swedish parties the political interested individuals tend to be less xenophobic, while the effect of sympathizing with the Sweden democrats and being political interested shows an increased level of xenophobia. The same result could be observed for Sweden democrats that consumed news via social media and internet, where an increased level of consumption resulted in increased level xenophobic attitudes. The study found no support for the effects of news consumption via social media/internet and political interest on the relation between Left party sympathizers and xenophobic attitudes.

<p>Recent research on cognitive control has focused on the learning consequences of high selective attention demands in selective attention tasks. The current study extends these ideas by examining the influence of selective attention demands on remembering. In Experiment 1, participants read aloud the red word in a pair of red and green interleaved words. Half of the items were congruent (the interleaved words were the same), and the other half were incongruent (the interleaved words were different). Following the study phase, participants completed a recognition memory test with a remember/know classification. A mirror effect was observed in the recognition memory data, with better memory for incongruent than for congruent items. In Experiment 2, context was only partially reinstated at test, and again better memory for incongruent compared to congruent items was observed. However, the processes supporting recognition decisions varied depending on context reinstatement, with only full context reinstatement resulting in differences in recollection for congruent and incongruent items. These results demonstrate that selective attention process demands associated with incongruent items affect episodic learning.</p> / Master of Science (MSc)

Approximately 10% of pregnant women take antidepressants. Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, has been shown to alter serotonergic signaling in the brain. However, the effects of SSRIs on peripheral serotonin (5HT) synthesis and/or signaling have largely been ignored. Serotonin in the gut is critical for intestinal function and dysregulation of this pathway is associated with intestinal disease. Therefore, the goal of this study was to determine the effects of perinatal exposure to the SSRI fluoxetine (Prozac®) on intestinal health in the offspring. Dams were given vehicle or fluoxetine hydrochloride (FLX 10 mg/kg/d; N=15) for 2 weeks prior to mating until weaning. We assessed markers of serotonergic signaling, inflammation, and composition of the gut microbiota in the offspring. Male offspring of fluoxetine-treated dams had significantly elevated serum levels of 5-HT and decreased expression of the 5HT2A receptor and MAO. In female offspring there was no effect of SSRI exposure to alter any components of serotonergic signaling. Although we did not find any evidence of increased inflammation following fluoxetine exposure, there were significant alterations in the composition of the gut microbiota in the exposed offspring. Male offspring of SSRIs-exposed mothers had changes in key components of the gut serotonergic system in association with elevated levels of serum 5-HT and alterations in the gut microbiota in adulthood. The impact of these changes on intestinal health and the reasons for the sex specific effects remain to be determined. / Thesis / Master of Science in Medical Sciences (MSMS)

This dissertation extends the media effects literature into the realm of social media. Scholars have long known that partisan news contributes to political polarization, but claim that such effects are often limited to those who tune into politics. Social media, however, can filter political information to those typically uninterested in politics. Because social media feature entertainment and political news in the same space, entertainment-seekers may inadvertently see political news that they normally avoid in traditional media contexts. Through a combination of observational research, survey experiments, and field experiments, I demonstrate that social media facilitate personal influence, drawing new audiences to political news. This increased exposure to partisan media contributes to political polarization, regardless of the ideological congruence between source and receiver, or of news- or entertainment-seeking habits of the audience. But the most important contributions of this dissertation are how it demonstrates the need for scholars to use innovative methods that incorporate personal influence into social media studies, and that it draws scholarly attention to inadvertent media effects for entertainment-seeking audiences. Social media bring political news to new audiences numbering in the millions. Political communication scholars would be remiss not to investigate their influence. / Political Science

Inflammatory bowel disease (IBD) is a serious, complex disease that is challenging to treat effectively and affects over 5 million people globally. Current treatment goals for both subtypes of IBD, Ulcerative Colitis (UC) and Crohn Disease (CD), focus on attaining and maintaining remission through anti-inflammatory agents, immunomodulators, or biologics. In spite of these treatments, more than 25% of patients require devastating surgical removal of part of their colon due to severe inflammation. Recent advances in our understanding of serotonergic effects beyond the central nervous system (CNS) provide encouragement for IBD treatment. The newest member of serotonin receptor family, the 5-HT7 subtype, is involved in the release of pro-inflammatory cytokines following stimulation by serotonin in the gastrointestinal tract (GIT). Khan et al have shown that inflammation associated with the DSS and DNBS mouse models of IBD is significantly attenuated in knock-out mice lacking the 5-HT7 receptor or mice treated with 5-HT7 selective antagonists. Previously reported 5-HT7 receptor antagonists (e.g., SB-269970) readily crosses the blood brain barrier (BBB) and are therefore not good choices for IBD treatments. Our group has identified a novel series of arylpiperazinyl lactones with high affinity and excellent selectivity for the 5-HT7. The aim of this project is to design, synthesize, and characterize new gamma-butyrolactone-based 5-HT7 ligands with high affinity, good selectively, acceptable drug-like properties, with limited access to the CNS. A total of 18 compounds were successfully synthesized and evaluated as potential new lead compounds for the treatment of IBD. / Pharmaceutical Sciences

Carbonic anhydrases (CAs, EC 4.2.1.1) are a class of metalloenzymes that catalyze the hydration of CO2 under physiologic conditions and are involved in many physiological and pathological processes. Modulation of CA activity, particularly CA inhibition is exploited pharmacologically for the treatment of many diseases such as cancer, glaucoma, edemas, mountain sickness. CA activation has been less frequently investigated till recently. Genetic deficiencies of several CA isozymes are reported in the literature and reflect the important role of carbonic anhydrases in human physiology and homeostasis. Activation of CA isozymes in brain have been correlated recently with spatial learning and memory. Based on these premises, activators of CA isozymes have the potential to alleviate mild dementias and to act as potential nootropic agents. In chapter 3, continuing our long-term interests towards the development of potent and selective CAAs, we carried out X-ray crystallographic studies with a small series of pyridinium histamine derivatives, previously developed as CAAs by our group. This study revealed important insights into the binding of this class of activators into the active site of CA II isozyme. A potent pyridinium histamine CAA 25i was successfully crystallized with CA II isozyme and was found to bind into the hydrophobic region of the active site, with two binding conformations being observed. This is one of the very few X-ray crystal structures of a CAA available. Based on the findings of this X-ray crystallographic study and building on our previously developed ethylene bis-imidazole CAAs, we advanced a novel series of lipophilic bis-imidazoles. Enzymatic assays carried out on purified human CA isozymes revealed several low nanomolar potent activators against various brain-relevant CA isozymes. Bis-imidazole 30e was found to be a nanomolar potent activator for CA IV, CA VA and CA IX. Due to their conjugated structure, these CAAs were also fluorescent and therefore were fully characterized in terms of photophysical properties, with several representatives proving to display very good fluorophores. The very good activation profile against several different CA isozymes, along with excellent fluorescence properties recommend these compounds as great molecular tools for elucidation of role of CA isozymes in brain physiology, as well as towards improvement of memory and learning. Focusing on inhibition of CA isozymes, it must be stressed that over the last decade a clear connection had been established between the expression of CA IX and CA XII and cancer. Since cancer is the second most common cause of death in the world, we explored the possibility to kill cancer cells via inhibition of different CA isozymes present in cancer cells. The membrane bound carbonic anhydrase IX (CA IX) isozyme represents a particularly interesting anticancer target as it is significantly overexpressed in many solid tumors as compared to normal tissues. In malign tissues this CA isozyme was found to play important role in pH homeostasis and promotes tumor cell survival, progression and metastasis. Thus, CA IX represents a potential biomarker and an appealing therapeutic target for the detection and treatment of cancer. CA IX can be targeted either through the development of small or large molecular weight, potent, and selective inhibitors or through the development of CA IX targeted drug delivery systems for selective delivery of potent chemotherapeutic agents. Building on these premises, in this dissertation, we also revealed our continuing efforts towards the development of potent and selective CA IX inhibitors along with their translation into the development of CA IX targeted drug delivery systems. In chapter 4, we designed a series of small molecular weight (MW) ureido 1,3,4-thiadiazole sulfonamide derivatives employing the “tail approach”, through the decoration of established sulfonamide CA inhibitor warheads with different tail moieties via ureido linker. The generated CAIs were tested against tumor associated CA IX and CA XII isozymes and off-target cytosolic isozymes CA I and CA II, and were revealed to be moderate to highly selective and nanomolar, even sub-nanomolar, potent CA IX inhibitors. Several potent pan-inhibitors were also identified in this section. We assessed these CAIs for their in vitro cell killing ability using MDA-MB 231 breast cancer cell line expressing CA IX and CA XII. The most efficient CAI proved to be ureido-1,3,4-thiadiazole-2-sulfonamide 69, which showed subnanomolar potency against purified human CA IX and CA XII isozymes, with good selectivity against CA I and CA II, and consistent, statistically significant cancer cell killing. In Chapter 5, continuing our efforts towards the development of potent and selective CA IX inhibitors, we designed, synthesized, characterized and evaluated a new series of PEGylated 1,3,4-thiadiazole-2-sulfonamide CAIs, bearing different PEG backbone length. We increased the PEG size from 1K to 20K, in order to better understand the impact of the PEG linker length on the in vitro cell killing ability against CA IX expressing cancer cell lines and also against a CA IX negative cell line. In vitro cell viability assays revealed the optimum PEG linker length for this type of bifunctional bis-sulfonamide CAIs in killing the tumor cells. The most efficient PEGylated CAI was found to bis-sulfonamide DTP1K 91, which showed consistent and significant cancer cell killing at concentrations of 10−100 μM across different CA IX and CA XII expressing cancer cell lines. DTP1K 91 did not affect the cell viability of CA IX negative NCI-H23 tumor cells, thus revealing a CA IX mediated cell killing for these inhibitors. In chapter 6, we decided to further explore the possibility of using CA IX as a targeting epitome for the development of a gold nanoparticle-based drug delivery system. We translated the oligoEG- and PEGylated CAI conjugates into efficient targeting ligands for gold nanoparticle decoration along with chemotherapeutic agent doxorubicin (Dox), in a novel multi-ligand gold nanoplatform designed to selectively release the drug intracellularly, in order to enhance the selective tumor drug uptake and tumor killing. We were successful in developing compatible CAI- and Dox- ligands for efficient dual functionalization of gold nanoparticles. Our optimized, CA IX targeted gold nanoplatform was found to be very efficient towards killing HT-29 tumor cells especially under hypoxic conditions, reducing the hypoxia-induced chemoresistance, thus confirmed the potentiating role of CA IX as a targeting epitome. / Pharmaceutical Sciences