Adsorption and reaction of CO on (Pd–)Al2O3 and (Pd–)ZrO2: vibrational spectroscopy of carbonate formation

γ-Alumina is widely used as an oxide support in catalysis, and palladium nanoparticles supported by alumina represent one of the most frequently used dispersed metals. The surface sites of the catalysts are often probed via FTIR spectroscopy upon CO adsorption, which may result in the formation of surface carbonate species. We have examined this process in detail utilizing FTIR to monitor carbonate formation on γ-alumina and zirconia upon exposure to isotopically labelled and unlabelled CO and CO2. The same was carried out for well-defined Pd nanoparticles supported on Al2O3 or ZrO2. A water gas shift reaction of CO with surface hydroxyls was detected, which requires surface defect sites and adjacent OH groups. Furthermore, we have studied the effect of Cl synthesis residues, leading to strongly reduced carbonate formation and changes in the OH region (isolated OH groups were partly replaced or were even absent). To corroborate this finding, samples were deliberately poisoned with Cl to an extent comparable to that of synthesis residues, as confirmed by Auger electron spectroscopy. For catalysts prepared from Cl-containing precursors a new CO band at 2164 cm−1 was observed in the carbonyl region, which was ascribed to Pd interacting with Cl. Finally, the FTIR measurements were complemented by quantification of the amount of carbonates formed via chemisorption, which provides a tool to determine the concentration of reactive defect sites on the alumina surface

Synthesis, Characterization and Application of intermetallic Pd-X (Ga, Zn) Nanoparticles derived from ternary Hydrotalcite-like precursors

A novel, feasible synthesis approach for supported intermetallic Pd2Ga and PdZn nanoparticles derived from Hydrotalcite-like compounds (HTlc) is introduced. Ternary HTlc with the nominal composition (Pd2+,M2+)0.70(M3+)0.30(OH)2(CO3)0.15 ∙ m H2O are synthesized by pH-controlled co-precipitation. Mg2+/Ga3+ and Zn2+/Al3+ are chosen as M2+/M3+ combinations to permit formation of the nanocrystalline Pd2Ga and PdZn intermetallic compounds on a porous MgO/MgGa2O4 and ZnO/ZnAl2O4 support, respectively. In addition, a PdMgAl HTlc is prepared as monometallic Pd reference compound on a MgO/MgAl2O4 support. Incorporation of Pd2+ into the HT structure requires octahedral coordination, while Pd2+ ions prefer square planar coordination in aqueous solution. At the same substitution degree of M2+ by Pd2+, complete insertion is achieved for PdZnAl HT. In case of PdMgGa and PdMgAl HT a minor fraction is present as segregated Pd2+ on the external surface of the platelet-like particles with a local environment similar to PdO, i.e. in a square planar coordination. A limit of incorporation into the HT lattice exists at < 1 mol% for the Pd2+ containing precursors. Upon thermal decomposition in reductive atmosphere, intermetallic and metallic nanoparticles ranging from below 2 nm to 6 nm in size and exhibiting monomodal particle size distributions are formed. Alloying of Pd with Ga and Zn changes the crystal structure as well as the electronic structure and leads to the increased formation of isolated adsorption sites at the surface. Furthermore, dynamic surface changes of intermetallic Pd2Ga nanoparticles were noticed at longer exposure time to CO and higher CO coverage. This is attributed to the decomposition into metallic Pd and Ga2O3. The nanostructured Pd2Ga catalyst shows excellent performance in the selective semi-hydrogenation of acetylene similar to a bulk Pd2Ga model catalyst. In comparison to the elemental Pd catalyst the selectivity to ethylene is drastically improved by formation of Pd2Ga. Interestingly, the nanostructered catalyst slowly activates in the feed gas. The activation is triggered faster by a treatment in oxidative atmosphere. These dynamics of the Pd2Ga nanoparticles can be explained by the interplay of surface decomposition into Pd0 and Ga2O3 in oxygen and reversal of the strong-metal support interaction state leading to an increased activity. Furthermore, increased activities and selectivities in methanol steam reforming and methanol synthesis from CO2 are observed for the Pd2Ga and PdZn nanoparticles in contrast to the unmodified Pd particles. These structurally modified Pd catalysts exhibit a considerably lower selectivity to CO and enhanced formation of methanol compared to the monometallic Pd catalyst.Abstract i Zusammenfassung iii Danksagung v List of Figures x List of Tables xiv List of Abbreviations xv Chapter 1: Introduction and Overview 1 1.1. Intermetallic compounds 1 1.2. Motivation 2 1.3. Synthesis strategy for binary Pd-X intermetallic nanoparticles 3 1.4. Pd-Ga system 6 1.5. The Pd-Ga intermetallic compound Pd2Ga 7 1.6. Pd-Zn phase system 9 1.7. Pd-Ga IMCs as selective acetylene hydrogenation catalysts 10 1.8. Pd based IMCs in methanol synthesis and methanol steam reforming 13 1.9. Aims of this work and thesis structure 15 1.10. References 17 Chapter 2: Intermetallic Compound Pd2Ga as a Selective Catalyst for the Semi-Hydrogenation of Acetylene: From Model to High performance Catalyst 21 2.1 Introduction 22 2.2 Experimental Section 24 2.2.1 Synthesis Procedures 24 2.2.2 Characterization Techniques 24 2.2.3 Catalytic Measurements 25 2.3 Results and Discussion 27 2.4 Conclusion 34 2.5 References 36 Chapter 3: Dynamic Surface Processes of nanostructured Pd2Ga catalysts derived from ternary Hydrotalcite-like Precursors 38 3.1 Introduction 39 3.2 Experimental 40 3.2.1 Synthesis conditions 40 3.2.2 Characterization 41 3.2.3 Catalytic performance in the selective hydrogenation of acetylene 43 3.3 Results and Discussion 44 3.3.1 Structural and textural properties of the precursor material 44 3.3.2 Reduction and intermetallic phase formation 49 3.3.3 Structural properties of Pd2Ga nanoparticles 54 3.3.4 IR characterization of supported Pd2Ga nanoparticles during exposure to CO 58 3.3.5 Catalytic performance 62 3.4 Conclusions 69 3.5 References 71 Supplementary Information 73 Chapter 4: Methanol Synthesis and Methanol Steam Reforming of Supported Pd2Ga and PdZn Intermetallic Nanoparticles 79 4.1. Introduction 80 4.2 Experimental 81 4.2.1 Synthesis conditions 81 4.2.2 Characterization 82 4.2.3 Catalytic performance 84 4.2.3.1 Methanol synthesis from CO2 84 4.2.3.2 Methanol steam reforming 85 4.3 Results and discussion 86 4.3.1 Properties of the HTlc precursors 86 4.3.2 Reducibility of the HTlc precursors and IMC formation 88 4.3.2.1 TPR and MS measurements 88 4.3.2.2 XANES measurements 91 4.3.3 Properties of the ex-HTlc samples after reduction 93 4.4 Catalytic properties of the IMCs 97 4.4.1 Methanol synthesis from CO2 97 4.4.2 Steam reforming of methanol 100 4.5 Conclusion 102 4.6 References 103 Supplementary Information 105 Chapter 5: Final summary and conclusion 108 Appendix xvii Curriculum vitae xvii Publications xvii Oral presentations xviii Patent application xviii Poster presentations xi

Effects of in vitro addition of infectious pancreatic necrosis virus (IPNV) on rainbow trout Oncorhynchus mykiss leucocyte responses

12 páginas, 5 figurasInfectious pancreatic necrosis virus (IPNV) did not replicate in rainbow trout macrophages cultured in vitro, but a limited increase in viral titer was observed when total leucocytes were infected with the virus. Macrophages did not respond directly to IPNV, in that IPNV did not trigger the respiratory burst of these cells, even when the macrophages were previously stimulated. Supematants were generated from leucocytes and macrophages exposed to the virus, using a variety of incubation periods and viral titers, to investigate whether virus stimulation induced the secretion of any immunomodulatory substances from these cells. No effect on macrophage responses was detected when these supematants were added to new macrophage monolayers. However, IPNV produced a significant reduction of LPS-induced B cell proliferation, in a dose-dependent manner, indicative of at least one immunosuppressive effect induced by this virus.This research was partially supported by The British Council (UK), the Ministerio de Educaci6n y Ciencia (Spain) and CICYT through Coordinated Action HB 93- 131 and Grant AGF93-0679-C02-02. Beatriz Novoa acknowledges the Ministerio de Education y Ciencia (Spain), for the research fellowship in the Department of Zoology, University of Aberdeen. UK.Peer reviewe

Computational and neuroimaging approaches to major depressive disorder

Major depression is a severely debilitating psychiatric condition with high prevalence and substantial economic impact. However, its aetiology is largely unknown, mechanistic understanding remains limited, and treatment outcomes are hard to predict. Recently, a “computational psychiatry” approach has emerged which embraces the idea of using computational models to link brain function, behaviour and psychiatric illness. This thesis describes the use of computational psychiatry tools and techniques to advance understanding of abnormalities in decision-making and neuronal activity associated with depressive illness. Behaviour during novel reward learning tasks was analysed from patients diagnosed with major depressive disorder and healthy controls. Formal computational modelling was used to show behavioural impairments associated with depression during both learning and decision-making phases. Depressed participants displayed lower memory of rewards and decreased ability to use internal value estimations during decision-making. Functional MRI results showed decreased reward signals in areas including the striatum were associated with depression symptoms. Computational models were used to generate latent variable time-series of internal value estimations which were used for model-based fMRI analyses. Reward value encoding in hippocampus and rostral anterior cingulate was abnormal in depression and anterior mid-cingulate (aMCC) activity was altered during decision-making. A signal encoding the difference between the values of the two options was also found in the aMCC, linking the behavioural model to localised brain function. Depressed patients showed decreased event-related connectivity between aMCC and rostral cingulate regions, implying impaired communication between value estimation and decision-making regions. A large community-based sample of participants reporting a range of depressive symptoms performed a different probabilistic reward learning task. Mood symptoms were associated with blunted striatal reward signals. Event-related directed medial prefrontal cortex to ventral striatum effective connectivity was abnormally decreased related to the severity of depression symptoms. A generative-embedding machine learning approach was used to classify never-depressed healthy controls from participants with current or past major depression. A support vector machine classifier achieved 72% diagnostic accuracy using estimated connectivity parameters as features. The thesis replicates previous reports of abnormal depression-related neural activity in areas including the striatum, hippocampus and prefrontal cortex using novel reward learning tasks. Findings support the theory about abnormal neural reward valuation in major depression being a core pathophysiological process which could be a target for treatment. The thesis also provides important novel evidence for decreased connectivity between prefrontal and limbic brain regions, and within different prefrontal areas in depression. It shows how abnormalities in reward value based decision-making may be related to abnormal reward activation and connectivity in the brain, supporting glutamatergic and cortical-limbic related theories of depression

Abnormal reward valuation and event-related connectivity in unmedicated major depressive disorder

BACKGROUND: Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression. METHODS: Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression. RESULTS: Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression. CONCLUSIONS: Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment

MicroRNAs as biomarkers in anti-tuberculosis drug-induced liver injury: a translational study from zebrafish to humans

Drug-induced liver injury is one of the leading causes of acute liver failure and is a serious barrier to drug development. Furthermore, it is a frequent adverse reaction to the antimicrobials used to treat tuberculosis, resulting in reduced treatment effectiveness, incomplete treatment, relapse and the development of antimicrobial resistance. The aim of the studies in this thesis were threefold, to investigate biomarkers of liver injury in patients receiving anti-tuberculosis medication, to investigate miRNA changes in zebrafish larvae due to drug-induced liver injury, and to develop a novel point of care diagnostic test for miR-122, a miRNA biomarker of liver injury. The novel biomarkers, microRNA-122 (miR-122) and cytokeratin-18 (K18) have been found to be diagnostic and prognostic in patients who overdose on paracetamol. A key question is, do these biomarkers retain their efficacy in the presence of infection? The circulating concentrations of miR-122 and K18 were defined in the following populations: healthy volunteers, active tuberculosis patients, latent tuberculosis patients, patients with non-tuberculous mycobacterial infection and HIV-tuberculosis coinfected patients. Circulating concentrations of miR-122 and K18 were not significantly different across these groups, indicating infection does not affect concentrations of miR-122 and K18. Furthermore, concentrations of miR-122 and K18 did not rise upon starting treatment. There was a significant correlation between the gold standard marker alanine aminotransferase (ALT) and both miR-122 and K18 demonstrating these biomarkers rise with elevations in ALT. In two individuals who developed drug-induced liver injury, miR-122 and K18 rose with ALT, suggesting these biomarkers have diagnostic potential for anti-tuberculosis drug-induced liver injury. To reduce the need for rodent studies a zebrafish larvae model of liver injury was developed. Reducing the number of rodent studies carried out reduces experimental costs and the use of zebrafish larvae enables rapid high-throughput experiments. Furthermore, using zebrafish larvae is in line with the “3Rs” (reduce, refine, replace) approach of animal use in science, with the replacement of rodents, a higher-order mammal, with the lower-order zebrafish larvae. Zebrafish larvae exposed to isoniazid and pyrazinamide developed liver toxicity as determined by mortality, fluorescent imaging and histology. In order to investigate pathways altered in anti-tuberculosis drug-induced liver injury and identify potential novel biomarkers small RNA sequencing was undertaken. Pathways were altered in anti-tuberculosis drug induced liver injury, including those associated with the metabolism of xenobiotics. Building on previous work by my group, zebrafish larvae were exposed to triptolide, a Chinese herbal medicine which induces liver injury. A method was developed to collect specific cell populations, hepatocytes and immune cells, from transgenic zebrafish larvae using fluorescence activated cell sorting (FACS). The miRNA changes in isolated cells populations were determined using qRT-PCR, and in whole fish using small RNA sequencing. Novel miRNA biomarkers of liver injury were identified from the small RNA sequencing data and translated in plasma samples from patients with anti-tuberculosis drug-induced liver injury. Two of these miRNAs rose with ALT in liver injury. A point of care test is needed for drug-induced liver injury, suitable for use in resource poor settings. A novel RNA toehold switch sensor was combined with a fluorescent and colorimetric outputs to provide a quantitative response to miR-122 concentrations. Toehold switches with a range of structures were developed and tested. Switches demonstrated varying levels of sensitivity and specificity for miR-122

Silicon Oxide Surface Segregation in CO Oxidation on Pd: An in situ PEEM, MS and XPS Study

The effect of silicon oxide surface segregation on the locally-resolved kinetics of the CO oxidation reaction on individual grains of a polycrystalline Pd foil was studied in situ by PEEM, MS and XPS. The silicon oxide formation induced by Si-impurity segregation at oxidizing conditions, was monitored by XPS and its impact on the global and local (spatially resolved) kinetics of the CO oxidation was determined by MS and PEEM. The results reveal a drastic inhibiting effect of silicon oxide on the Pd reactivity towards CO oxidation, manifested both in the collapse of the global CO2 formation rate and in the modified local reactive properties of individual Pd micrograins. The presence of adsorbed oxygen on the Pd surface effectively enhances the silicon segregation to the Pd surface