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- Friberg, Andrew S, 1979-
(författare)
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Standardization of Islet Isolation and Transplantation Variables
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Currently, the transplantation of islets of Langerhans is a viable means to maintain control of blood sugar levels and reduce the risk of hypoglycemia in defined populations with brittle type I diabetes mellitus or those requiring pancreatectomy. However, the process of islet isolation is highly variable and not all isolations result in islet numbers or quality suitable for transplantation. This thesis aimed to improve transplantation success through optimization and standardization of the isolation process and to identify pretransplant variables associated with early islet engraftment. A previously disregarded enzyme activity, tryptic-like activity (TLA), has been identified to influence pancreas digestion efficiency and islet isolation success in both the preclinical and clinical situations. For human pancreases, islet isolation success rates improved from 0% in the lowest TLA group to over 50% in the highest TLA groups without affecting islet quality. These findings should help standardize evaluation of enzymes for clinical islet isolation. A closed, automated, pump-made gradient system was compared to the open, manual method for islet separation. No differences were observed in expected gradient volumes, islet yields or total purities between the two methods. The pump-made gradient system successfully removed manual influences on density gradient production while fulfilling regulatory requirements for closed system processing. Islet quantification was evaluated with computer-assisted digital imaging analysis (DIA) and a semi-closed assessment system. By using the DIA system method, which measures islet purity and pellet volume instead of manual counting methods, variation in islet counts and purity reduced by almost half. By using a transplant outcome measurement of C-peptide adjusted by blood glucose and creatinine, we identified four pretransplant factors that affect early transplant outcome. Of the four factors, one was related to the organ transport time, one to function of the islets, and two to the transplanted tissue volume. When these four factors were put into a predictive model, it accounted for about 40% of the transplant outcome. The work contained in this thesis identifies and optimizes a number of critical elements related to islet isolation and transplantation protocols.
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| 2. |
- Albertsson, Daniel M, 1957
(författare)
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Hip fracture prevention by screening and intervention of elderly women in primary health care
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hip fracture prevention by screening and intervention of elderly women in Primary Health Care Daniel Albertsson Background – One in four Swedish women suffers a hip fracture (HF). In order to identify high-risk women we developed clinical 4-item scores as the FRAMO (Fracture and Mortality) Index, evaluated heel bone mineral density (BMD) and undertook interventions to improve mobility, reduce falls and HF. Methods - In pilot study 1998, a questionnaire regarding HF risk factors was sent to100 elderly women, with follow-up in 2001. Based on questionnaire 2001 sent to 1498 women aged ≥70, participants were analyzed with FRAMO Index (Risk Model I) for HF, fragility fracture (FF) and mortality in 2002–2003. A questionnaire regarding HF risk was 2003 returned by 285/435 women in the intervention population and heel BMD was assessed by portable dual X-ray laser absorptiometry (DXL), and correlated with 2-year incident HF and FF. Heel BMD was compared to hip BMD. In the controlled cohort intervention study, 296 (I=103, C=193) women were at high risk for HF (in Risk Model II). House calls were made to 61 % in intervention group, initiating exercising and home hazard reduction. After BMD determination pharmacological treatment was considered for 80 %. We evaluated mobility outcomes from questionnaires 2001 and 2004 and incident fractures in 2004–2005. Results - The 1998 questionnaire was answered by 92%; 34% had needs for fracture prevention. The 2001 questionnaire was returned by 83% (n=1248). Four items – age ≥80, weight <60kg, prior fragility fracture and using arms to rise from sitting - were combined in FRAMO Index. The 2-year HF risk was 0.8% for 63% with scores 0–1, and 5.4% (OR 7.5; 95%CI 3.0–18.4) for remaining 37% women with scores 2–4, having a 23.7% mortality risk. During 2004–2005, 7 HFs and 14 FFs occurred among the 285 women in intervention group, 60% of whom had heel osteoporosis (≤ -2.5 SD). The revalidated FRAMO Index showed HF OR 5.9 and FF OR 4.4. Heel BMD showed HF OR 2.7 and FF OR 2.3 for each SD decrease. Combining FRAMO Index + prior fragility fracture + low heel BMD yielded an annual HF risk of 7.8% for 11% and 0.4% for 89%. In the intervention group, we found less women with inability to rise (OR 0.21) and fewer falls (OR 0.46) in 2004, in women with initially impaired mobility. Home exercise was more common in intervention group (RR 2.1). Women with impaired rising ability who home exercised improved (p=0.03). Three interventions seemed related to improvement in rising ability on multivariate analysis; current home exercise, calcium-vitamin D3 treatment and previous group exercise (p=0.04–0.06). Two HFs occurred in the intervention group vs 11 in controls (OR 0.33 and p=0.23). Conclusion – Study questionnaires were feasible in PHC. The FRAMO Index yielded good fracture and mortality prediction. Heel BMD showed increased HF and FF risk. Heel osteoporosis prevalence was high. Hip osteoporosis corresponded to a heel DXL level of around -3.3 SD. Clinical risk factors combined with very low heel BMD defined a small high risk group for HF. Intervention group subjects with impaired mobility and high HF risk improved their mobility more than controls, one year after major multi-factorial intervention. Home exercise, group exercise and calcium- vitamin D treatment seemed related to improved rising ability. This risk assessment and intervention program with 1–2 years duration appears useful in population-based HF prevention.
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| 5. |
- Lind, Thérèse, 1989-
(författare)
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Financial literacy, motivated reasoning, and gender : essays in behavioral economics
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I wrote this thesis to create a better understanding of how individual characteristics influence our feelings, our behavior and our way of interpreting information. My focus is on financial behavior and financial information, however I also consider a political context. I investigate the (usually) enabling abilities of financial literacy and numeracy. I also consider impediments such as stereotype threat and motivated reasoning, which can prevent people from engaging in certain behaviors or from interpreting information objectively. Both processes stem from valued beliefs and psychological foundations, consequently peoples’ efforts, decisions, and evaluations are based on them.The first essay, “Competence, confidence, and gender: The role of perceived and actual financial literacy in household finance,” broadens our understanding of the benefits of financial competence. I contrast perceived and actual levels of financial literacy, and consider the role of numeracy and cognitive reflective ability. I conclude that perceived and actual levels of financial literacy positively affect behavior and wellbeing; however, perceived financial literacy more so than actual financial literacy. No such effect is observed for numeric ability and cognitive reflection. Furthermore, women are more anxious about financial matters even though they tend to engage more frequently in the considered financial behaviors.The second essay, “Threatening finance? Examining the gender gap in financial literacy,” continues my exploration of the relationship between gender and financial literacy. In a series of studies, I investigate whether the observed gender gap in financial literacy can be identified in nonnumerical contexts, if it can be associated with confidence in financial matters, and if it can be attributed to stereotype threat, which posits that inbuilt prejudices about gender and finance undermine women’s performance of tasks that involve finance. The results show that the observed gender gap in financial literacy is robust even in nonnumerical financial contexts and suggest that a stereotype threat for women in the financial domain might be present. The gender gap in financial literacy could not be attributed to a difference in (displayed) confidence.In the third essay, “Preferences for lump-sum over divided payment structures,” I investigate whether or not people display systematic preferences for lump–sum or divided payment structures and how these preferences differ in gain (benefit) and loss (payment) situations. I investigate what happens when payments belong to a single underlying event, such as when people can choose to pay immediately or in installments. I also examine whether or not individual differences in time preferences, risk preferences, numeracy, and financial literacy are associated with preferences for one payment structure or the other. The aggregate results show a tendency for people to prefer obtaining and paying money in lump sums. I find no systematic indication that the considered individual differences play a role in this type of decision.The fourth essay, “Motivated reasoning when assessing the effect of refugee intake,” inquires into differences in worldview ideology, whether people identify as nationally or globally oriented, hinder them from objectively interpreting information. I use an experiment to find out if people display motivated reasoning when interpreting numerical information about the effects of refugees on the crime rate. Our results show evidence of motivated reasoning along the lines of worldview ideology. However, individuals with higher numeric ability were less likely to engage in motivated reasoning, leading to the conclusion that motivated reasoning is more likely to be driven by feelings and emotional cues than by deliberate analytical processes.
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| 6. |
- MacMillar, Susanna, 1976-
(författare)
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Isotopes as Mechanism Spies : Nucleophilic Bimolecular Substitution and Monoamine Oxidase B Catalysed Amine Oxidation Probed with Heavy Atom Kinetic Isotope Effects
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the study of reaction mechanisms by means of kinetic isotope effects (KIEs). Studies of the nucleophilic bimolecular substitution (SN2) reaction had the dual purpose of improving our fundamental understanding of molecular reactivity and assessing the ability of kinetic isotope effects to serve as mechanistic tools. The transition state of the SN2 reaction between a cyanide ion and ethyl chloride in tetrahydrofuran was found to be reactant like and only slightly tighter than has been found previously for the same reaction in dimethyl sulphoxide. One conclusion was that the transition-state structure in this reaction was predicted fairly well by the theoretical calculations, even without solvent modelling. The SN2 reactions between cyanide ions and para-substituted benzyl chlorides were found to have reactant-like transition states, of which the Cα-Cl bond was most influenced by the para-substitution. Theoretical calculations indicated that the chlorine KIEs could be used as probes of the substituent effect on the Cα-Cl bond if bond fission was not too advanced in the transition state. Furthermore, the nucleophile carbon 11C/14C KIEs were determined for the reactions between cyanide ions and various ethyl substrates in dimethyl sulphoxide.Precision conductometry was employed to estimate the aggregation status of tetrabutylammonium cyanide in tetrahydrofuran and in dimethyl sulphoxide, which is of interest as tetrabutylammonium cyanide is frequently used as the nucleophilic reagent in mechanistic investigations and synthetic reactions. The tendency for ion-pair formation was found to be very slight, significant, and very strong in dimethyl sulphoxide, water, and tetrahydrofuran, respectively. The nitrogen kinetic isotope effect on monoamine oxidase B catalysed deamination of benzylamine was determined in an attempt to obtain conclusive evidence regarding the mechanism of the oxidation. Monoamine oxidase is an important drug target in connection with the treatment of, for example, depression and Parkinson’s disease, and knowledge on how the enzyme effects catalysis would facilitate the design of highly selective and efficient inhibitors.
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| 7. |
- Martinez Molina, Daniel, 1979-
(författare)
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Membrane Protein Tailoring and Structural Studies of Leukotriene C4 Synthase
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite a dramatic increase in the number of proteins that have been structurally characterized in recent years, there are still less than 200 unique structures of membrane proteins known today. This is only 1% of the total number of unique protein structures found in structural databases worldwide. There are several reasons for this hindered progress in the structure determination of membrane proteins; it is difficult to generate membrane proteins in recombinant expression systems and it requires the use of appropriate detergents, both for membrane extraction and to keep them stable in solution. This makes isolation and purification problematic. Importantly, once isolated, these proteins are notoriously difficult to crystallize for X-ray structure determination. In this thesis, I present two techniques that can be used to increase the likelihood of success in the structural determination of membrane proteins. I started by focusing on problems that occur at an early stage of the process, where I developed a directed-evolution method to overcome problems with low yields during membrane protein production. In addition, I describe a screen for optimal detergent usage when purifying and crystallizing recombinant membrane proteins in eukaryotic hosts. The crystal structure of human Leukotriene C4 synthase has been solved. This is the first human membrane protein whose structure has been solved at high resolution. The model provides a structural basis for the formation of potent lipid mediators, which are implicated in the pathophysiology of asthma and chronic inflammation. Furthermore, the structure reveals insight into how specificity can be achieved for lipophilic substrate molecules. In addition, I have determined the crystal structure of a hexahistidine tag and use it to describe the molecular basis of the single most used chromatography method, IMAC.
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| 8. |
- Nowinski, Daniel, 1972-
(författare)
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Regulation of Fibroblast Activity by Keratinocytes
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the healing of cutaneous wounds, paracrine communication between keratinocytes and fibroblasts regulates cell differentiation, proliferation and synthesis of extracellular matrix. Deficient epidermal coverage, as seen in burn-wounds, frequently results in hypertrophic scars. Previous studies suggest that keratinocytes downregulate the production of collagen and profibrotic factors in fibroblasts. We hypothesized that keratinocytes downregulate the expression of the profibrotic factor connective tissue growth factor (CTGF) in fibroblasts, and regulate fibroblast expression of genes important to wound healing. In keratinocyte-fibroblast cocultures, keratinocytes downregulated CTGF mRNA and protein in fibroblasts, through the secretion of interleukin-1 (IL-1) α. Using Affymetrix DNA microarrays, it was demonstrated that factors from keratinocytes regulate the expression of 69 genes important to wound healing. The regulation of 16 of these genes was confirmed by Northern blotting, and IL-1α from keratinocytes regulated all the 16 genes examined. IL-1-mediated CTGF gene regulation was further investigated. Both IL-1 isoforms, α and β, suppressed CTGF expression through an inhibition of CTGF promoter activity. Interestingly, transforming growth factor-β-stimulated Smad phosphorylation was not affected by IL-1. Finally, we hypothesized that CTGF is downregulated in burn wound by split-thickness skin grafting and that the expression of CTGF is suppressed during reepithelialization. The expression of CTGF protein was decreased in successfully skin-grafted wound areas, and increased in open, granulating burn wounds. Moreover, CTGF protein expression was absent beneath the migrating edge of reepithelialization ex vivo. In conclusion, we demonstrate that, in in vitro models, keratinocyte-derived IL-1α regulates the expression of CTGF and other genes with importance to wound healing. Furthermore, it is shown that CTGF expression is suppressed by epidermal wound coverage i burn wounds. These findings may have implications for the understanding of keratinocyte-fibroblast interplay during wound healing and in hypertrophic scar pathogenesis.
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| 9. |
- Schlesinger, Daniel, 1982-
(författare)
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Molecular structure and dynamics of liquid water : Simulations complementing experiments
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Water is abundant on earth and in the atmosphere and the most crucial liquid for life as we know it. It has been subject to rather intense research since more than a century and still holds secrets about its molecular structure and dynamics, particularly in the supercooled state, i. e. the metastable liquid below its melting point. This thesis is concerned with different aspects of water and is written from a theoretical perspective. Simulation techniques are used to study structures and processes on the molecular level and to interpret experimental results. The evaporation kinetics of tiny water droplets is investigated in simulations with focus on the cooling process associated with evaporation. The temperature evolution of nanometer-sized droplets evaporating in vacuum is well described by the Knudsen theory of evaporation. The principle of evaporative cooling is used in experiments to rapidly cool water droplets to extremely low temperatures where water transforms into a highly structured low-density liquid in a continuous and accelerated fashion.For water at ambient conditions, a structural standard is established in form of a high precision radial distribution function as a result of x-ray diffraction experiments and simulations. Recent data even reveal intermediate range molecular correlations to distances of up to 17 Å in the bulk liquid.The barium fluoride (111) crystal surface has been suggested to be a template for ice formation because its surface lattice parameter almost coincides with that of the basal plane of hexagonal ice. Instead, water at the interface shows structural signatures of a high-density liquid at ambient and even at supercooled conditions.Inelastic neutron scattering experiments have shown a feature in the vibrational spectra of supercooled confined and protein hydration water which is connected to the so-called Boson peak of amorphous materials. We find a similar feature in simulations of bulk supercooled water and its emergence is associated with the transformation into a low-density liquid upon cooling.
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| 10. |
- Strömbäck, Camilla, 1989-
(författare)
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Self-Control, Financial Well-Being, and Motivated Reasoning : Essays in Behavioral Finance
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this thesis is to improve our understanding of how individual differences in intuitive and analytic decision making are associated with people’s behavior as well as their well-being. The first three essays investigate, in turn, how self-control—a typical System 2 driven ability—correlates with financial behavior, financial well-being, and affective forecasting ability. The fourth essay leverages an experimental design, in which a randomized treatment attempts to inhibit the use of System 2 processing by individuals by setting them under time pressure, while measuring how they interpret numerical information.The first essay, Does Self-Control Predict Financial Behavior and Financial Well-Being?, describes how variation in self-reported individual differences in self-control, optimism and deliberativeness predicts financial behavior and financial well-being. Data was collected by means of an online survey distributed to a representative, adult Swedish sample. Results indicate that individuals with better self-control were more likely to engage in sound financial behaviors, were less anxious about financial matters, and felt more secure in their current and future financial situation than individuals displaying lower levels of self-control.The second essay, Subjective Self-Control but Not Objective Measures of Executive Functions Predicts Financial Behavior and Well-Being, is a follow-up study of the first essay. Apart from using the same self-reported measures of self-control, optimism, and deliberativeness as essay one does, this analysis additionally includes an extensive test battery of objective performance measures of executive functions and intelligence. Findings suggest that, while self-reported self-control predicts both financial behavior and subjective financial well-being, neither of the executive functions, nor intelligence do so. This indicates that an ability to form good habits and avoid temptation is more important for sound financial behavior and financial well-being than actual inhibitory control.The third essay, Better Self-Control Does Not Imply Fewer Affective Forecasting Errors, explores whether individual-level differences in self-control can explain observed variation in affective forecasting ability. Moreover, it assesses whether participants with strong self-control are more likely to make “optimal choices” in an intertemporal choice task: i.e. choices that maximize their own expected happiness. To test this, the study leveraged a laboratory experiment with a student sample in Linköping and Stockholm. Study results uncover no evidence of self-control predicting affective forecasting ability. Equally, self-control seemingly had no effect on the probability of individuals’ choosing happiness maximizing options.The fourth essay, Motivated Reasoning, Fast and Slow, investigates whether prior beliefs may hinder individuals from interpreting information about immigration and gender quotas correctly: a process commonly referred to as motivated reasoning. In general terms, motivated reasoning can be conceptualized as an intuitive or analytic process. Testing the prevalence of this form of sense-making, we ran an online experiment where half the respondents were tasked to interpret numeric information under time constraints, and the rest without said constraints. Findings provide clear evidence of the existence of motivated reasoning with regards to issues of both immigration and gender quotas. Numeric ability seemingly reduced the probability of individuals to engage in motivated reasoning, while time pressure had no effect on said likelihood. Hence, results suggest that motivated reasoning is an intuitive, rather than an analytic process.
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