| 1. |
- Berggren, Gustav, 1980-
(författare)
-
Mimicking Nature – Synthesis and Characterisation of Manganese Complexes of Relevance to Artificial Photosynthesis
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of efficient catalyst for water oxidation is of paramount importance to artificial photosynthesis, but before this can be achieved a deeper understanding of this reaction is essential. In nature this reaction occurs in a tetranuclear Mn-cluster which serves as the work-horse of oxygenic photosynthesis. This thesis summarises my efforts at developing molecular systems capable of mimicking this complex employing a biomimetic approach. Three different approaches towards this goal are described here-in. The first section describes a screening study, in which a number of manganese complexes were tested to see whether or not they were capable of catalysing the formation of dioxygen when treated with different oxidants (Papers I). For those reactions in which dioxygen formation was observed the reactions were repeated in labelled water and the incorporation of labelled O-atoms was studied by mass spectrometry. This allowed us to determine to what extent water was the source of the evolved dioxygen (Papers II-III). In Chapter three a reported catalyst and a derivative thereof is studied in depth. The influence of changes to the ligand on the oxygen–oxygen bond forming reaction could unfortunately not be reliably addressed, because of the instability of the complexes under “catalytic” conditions. Nevertheless, the study allowed us to revise the “carboxylate shift”-mechanism suggested in the literature (Papers IV-V). Chapter four describes the continuation of my work on ligands featuring the carboxylate ligand motif first introduced in Chapter three. In this study ligands containing multiple binding pockets were designed and synthesised (Paper VI). A better understanding of the mechanism in the natural water oxidising enzyme will facilitate the design of biomimetic complexes, this is discussed in Chapter five. In this work model complexes (Paper VII) are used to study the mechanism by which natures own water oxidising catalyst performs this reaction.
|
|
| 2. |
- de Sousa, Pedro F. M., 1977-
(författare)
-
Chemometrics : Unravelling information from complex data generated by modern instruments
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chemometrics is a discipline dedicated to solving problems arising from complicated analytical systems, combining statistics, mathematics, and computational programming languages.This thesis is based on the work developed in four scientific projects published as papers in scientific journals. The studies developed in these projects have been essentially focused on a data analysis perspective, interpreting complicated data by means of algorithms, employing chemometrical methodologies. Several chemometrical approaches, based on multivariate data analysis and signal processing algorithms have been studied and employed in each project. Most of the data analysis problems studied these projects are related to liquid chromatography hyphenated to mass spectrometry systems, including tandem mass spectrometry. One of the projects has been related to spectrophotometric data.Chromatographic peak shifts have been attributed to lack of control of the nominal chromatographic parameters. The purpose of the work presented in Paper I was to study retention time data, obtained experimentally by provoking peak shifts with controlled effects, to demonstrate that there are patterns associated with such changing factors affecting chromatographic processes. PCR (Principal Component Regression) models were calculated for each compound (98 compounds), using the retention time data of each compound as responses (y), and the retention time data of the remaining compounds as regressors (X). The results demonstrate that the peak shifts of each compound across samples are correlated with the peak shifts of the other compounds in the chromatographic data. This work confirmed a previous work, where an algorithm was developed to improve alignment of peaks in large number of complex samples, based on peak shift patterns.Partial Least Squares (PLS) is one of the mostly used chemometrics techniques. In the work presented in Paper II, a previously reported modified PLS algorithm was studied. This algorithm was developed with the purpose of not generating overfitting models with increasing noise in X, which happens with the classical PLS. However, the results in less-noisy data were not as good as the classical PLS. From this study, we have developed another modified algorithm that does not overfit with increasing noise in X, and it converges with the solutions of the classical PLS in less-noisy data.DNA adductomics is a recent field in omics that studies modifications in the DNA. The goal of the project in Paper III was to develop a program with a graphical interface to interpret LC-MS/MS using a data independent acquisition method, to identify adducts in DNA nucleosides. The results were compared with those performed manually. The program detected over 150 potential adducts whereas manually, in a previous work, only about 25 were found. This program can detect adducts automatically in a matter of seconds.Cancer has been associated with processes that are related to exposure to pollutants and the consumption of certain food products. This process has been related to electrophilic compounds that react with DNA (adducts). When DNA modifications occur, often defense mechanisms in the cell are triggered often leading to the rupture of the cell. Fragments of DNA (micronuclei) are then roaming in the blood stream. In this work (Paper IV), electrophilic additions to hemoglobin (adducts) and the expression of micronuclei in blood samples from 50 children were studied. One of the goals of the project was to find correlations between the adducts in hemoglobin and the expression of micronuclei. PLS was used to model the data. However, the results were not conclusive (R2 = 0.60), i.e., there may be some trends, but there are other variables not modelled that may influence the variance in expression of micronuclei.
|
|
| 3. |
|
|
| 4. |
- Kreutz, Joakim, 1973-
(författare)
-
Dismantling the Conflict Trap : Essays on Civil War Resolution and Relapse
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Countries that have experienced civil war suffer a greater risk for new conflict than countries with no prior history of civil war. This empirical finding has been called a conflict trap where the legacy of previous war - unsolved issues, indecisive outcomes, and destruction – leads to renewed fighting. Yet, countries like Cambodia, El Salvador, Indonesia, and Mozambique have managed to overcome decade-long conflicts without relapse. This dissertation addresses this empirical puzzle by seeking to dismantle the conflict trap and look at microlevel explanations for civil war resolution and relapse. It adds to existing scholarship in three ways: first, by using disaggregated empirics on war termination and how fighting resumes; second, by exploring government agency in conflict processes; and third, by disaggregating rebel organizations. Essay I present original data on the start and end dates and means of termination for all armed conflicts, 1946-2005. Contrary to previous work, this data reveal that wars does not always end through victory or peace agreement, but commonly end under unclear circumstances. Essay II addresses how developments exogenous to the conflict influence governments’ decision to engage in a peace process. The results show that after natural disasters when state resources need to be allocated towards disaster relief, governments are more willing to negotiate and conclude ceasefires with insurgents. Essay III focuses on the post-conflict society, and posits that security concerns among former war participants will push them towards remobilizing into rebellion. The findings indicate that if ex-belligerent elite’s security is compromised, the parties of the previous war will resume fighting, while insecurity among former rank-and-file leads to the formation of violent splinter rebel groups. Finally, Essay IV seeks to explain why governments sometimes launch offensives on former rebels in post-conflict countries. The results show that internal power struggles provide leaders with incentives to use force against domestic third parties to strengthen their position against intra-government rivals. Taken together, this dissertation demonstrates that there is analytical leverage to be had by disaggregating the processes of violence in civil war and post-conflict societies, as well as the actors involved – both the government and rebel sides.
|
|
| 5. |
- Liljeblad, Jonathan F. D., 1978-
(författare)
-
A Spectroscopic Study of Interfacial Films: Internal Structuring, Stability, and Hydration
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Monolayers of molecules are capable of completely changing the nature of surfaces and their interactions with the surroundings despite their almost negligible thickness. In the research presented in this doctoral thesis the surface specific technique Vibrational Sum Frequency Spectroscopy (VSFS) was combined with the Langmuir trough to investigate various manifestations of monolayers, such as biomimetic membranes, mono methyl branched long chain fatty acids in contact with air, and hydrophobic silane monolayers in contact with water.VSFS was applied to in situ studies of the oxidative degradation of Langmuir monolayers of 1,2-diacylphosphocholines with identical C-18 chains featuring various degrees of unsaturation. The monolayer area and vinyl CH signal intensity were probed at constant surface pressure to monitor the degradation. The rapid degradation of the unsaturated lipids in contact with the ambient air is attributed to oxidation of the C=C bonds mediated by reactive species in the air and can be inhibited by purging the compartment surrounding the monolayer with nitrogen.The molecular structure and order of Langmuir monolayers of 1,2-distearoyl-phosphocholine (18:0 PC) and their hydrating water were investigated at different surface pressures using VSFS. The monolayers are conformationally well ordered at all surface pressures and the signal intensity increases due to larger molecular number density at increasing surface pressures. Also, water signals with different vibrational frequencies are observed in different polarization combinations.Additionally, a selection of common phospholipids (18:0 PC, 18:0 PC-D83 and 18:0 PS) were Langmuir-Blodgett (LB) deposited on CaF2 substrates and the CH- and OH-stretching regions as well as lower wavenumber regions were probed using VSFS. The orientation of the conformationally well ordered aliphatic chains was determined to be approximately perpendicular to the sample surface.Monolayers of eicosanoic acid, its iso (19-MEA), and anteiso (18-MEA) analogues were investigated with VSFS, AFM imaging, and the Langmuir trough. The EA forms smooth, featureless monolayers when deposited on silica, while 19-MEA and 18-MEA form 10 -50 nm large domains with homogeneous size distribution. It was not possible to discriminate between the monolayers of racemic and chiral 18-MEA using any of the techniques employedThe influence of the experimental geometry on the SF spectral shape and en-hancement at and near total internal reflection conditions (TIR) were systematically investigated by comparing simulations with recorded data from a hydrophobized silica / water interface. The data agree qualitatively, but not quantitatively, with the simulations, and the reasons were critically discussed.The water structure next to ordered and disordered hydrophobic silane monolayers on silica was investigated using VSFS. The results indicate that the structure of water next to a well ordered hydrophobic monolayer, with the exception of the first layer of water molecules, is not much different from that in the isotropic bulk. This is in contrast to the previous notion where such monolayers were assumed to induce a more ordered interfacial water structure.
|
|
| 6. |
- Roos-Engstrand, Ester, 1962-
(författare)
-
T cells in chronic obstructive pulmonary disease
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Tobacco smoking is the main cause of chronic obstructive pulmonary disease, COPD, but the mechanisms by which cigarette smoke induces COPD are still elusive. T lymphocytes have been implicated in the pathogenesis of the disease, but their role in the airway inflammation in COPD is not fully understood. The aim of this thesis was therefore to address T lymphocyte subsets and their activation in the airways of subjects with COPD, in comparison to smokers with normal lung function (S) and never smokers (NS). Methods: Subjects with moderate to severe COPD were recruited along with controls. They were all non-atopic and clinically stable, without any exacerbation during at least three months prior to inclusion. Only medication with short-acting β2-agonists and/or anti-cholinergic drugs was permitted. All subjects underwent bronchoscopy with endobronchial mucosal biopsy sampling as well as bronchial wash, BW, and bronchoalveolar lavage, BAL, collection. Biopsies were immunohistochemically stained for inflammatory cells and markers. BW and BAL fluids were prepared for differential cell counts. Soluble markers were measured in BW and lymphocyte subsets were determined in BAL using flow cytometry. Results: In biopsies, an increase in epithelial CD3+ and CD8+ cells was found in COPD, compared to NS. In BAL fluid, CD8+ cells were enhanced, whereas CD4+ cells were reduced in subjects with COPD and S, compared to NS. Furthermore, CD4+ and CD8+ cells were more activated both in COPD and S, in terms of increased expression of CD25, CD69 and HLA-DR. NKG2D-expressing CD8+ T cells in BAL fluid were enhanced in both COPD and S. CD4+CD25bright cells were upregulated in COPD and S, suggesting the presence of regulatory T cells. Further analyses of T cell subsets with the more specific markers for regulatory T cells, FoxP3 and CD127, indicated a smoking-induced expansion of non-regulatory T cells, which tended to normalize after smoking cessation in COPD. Currently smoking subjects with COPD still expressed high proportions of activated non-regulatory CD4+ T cells. The data on FoxP3 expression further indicated that the increase in CD25 expression in COPD and S was not only associated with the expansion of regulatory T cells. As CD127 expression is reported to be inversely associated with FoxP3, the data indicate the expansion of a non-regulatory CD25+ population in smokers and patients with stable COPD. The immunohistochemical staining for the NKG2D ligands MICA and MICB on epithelial cells was unchanged. Conclusion: The results of this thesis suggest a role for CD4+ and CD8+ T-cells in clinically stable COPD, indicating that T-cells are of importance in the long-term inflammatory response in COPD. Regardless of current smoking habits, activated CD8+ T lymphocytes were found to be increased in BAL fluid from subjects with COPD, suggesting that changes in CD8+ T cells are associated with a persistent immune response and, thus, of importance in COPD pathogenesis. In contrast, the expansion of non-regulatory CD25+CD4+ cells in BAL fluid seemed to be preferentially smoke-related. In summary, the data indicate that, among airway T cells, changes in CD8+ cells seem to be highly associated with COPD pathogenesis, whereas changes in CD4+ cells appear to be related to cigarette smoke-induced responses. Further, a non regulatory population of helper T cells was identified in BAL fluid of COPD patients, which may contribute to the persistent cytotoxic T cell responses.
|
|
