Enantioselective reactions are one of the ways to produce pure chiral compounds. Understanding the basis of this selectivity makes it possible to guide enzyme design towards more efficient catalysts. One approach to study enzymes involved in chiral chemistry is through the use of computational models that are able to simulate the chemical reaction taking place. The potato epoxide hydrolase is one enzyme that is known to be both highly enantioselective, while still being robust upon mutation of residues to change substrate scope. The enzyme was used to investigate the epoxide hydrolysis mechanism for a number of different substrates, using the EVB approach to the reaction both in solution and in several enzyme variants. In addition to this, work has been performed on new ways of performing simulations of divalent transition metals, as well as development of new simulation software.

The Diesel Oxidation Catalyst (DOC) is subjected to harsh conditions, causing its performance to diminish over time as the result of different aging mechanisms, which either decreases or lowers the accessibility to the catalyst’s active sites. Previous work using chemisorption to quantify aging progression has resulted in a reproducibility of 17%. In this study it has been attempted to lower this, while also performing performance evaluations to see if correlations exist between dispersion and Light-Off Temperature (LOT). Two catalysts have been investigated, LLC (Low Loading Catalyst) and HLC (High Loading Catalyst). These were hydrothermally aged at 600 C, 700 C and 800 C. In addition to these, two HLC engine cell samples were also investigated. To ensure sample homogeneity, different sample preparation methods were investigated. Catalyst samples were crushed, or had their washcoat layer removed, or were milled and then sieved. A total of 5 runs were done using fresh catalysts of LLC and HLC to calculate the standard deviation. Evaluation of performance was done on all samples using Synthetic Catalyst Activity Testing (SCAT). It was deemed that the only viable sample preparation method was to mill and sieve as other methods would be hard to reproduce. The results showed that the reproducibility for LLC was %STD = 4% and for HLC %STD = 2%. For LLC, a correlation between catalytic activity and dispersion was found. The activity dropped with respect to the dispersion in a close to linear fashion without a large effect on BET surface area. For HLC the dispersion decreased largely upon hydrothermal aging, however no correlation was found with the activity; only when aged at 800 C a significant change in LOT was noted. The BET surface area measurements were inconsistent. Lower dispersion sometimes resulted in higher surface area. Engine cell samples exhibited notable decrease in dispersion, but not in surface area, and did not correlate to the hydrothermally aged catalysts, which might be due to other effects inhibiting CO chemisorption during measurements. / Dieseloxidationskatalysatorn (DOC) utsätts för tuffa förhållanden, vilket medför att dess prestanda minskar med tiden på grund av olika åldringsmekanismer, vilka antingen minskar dess aktiva säten eller minskar tillgängligheten till dessa. Tidigare studier då kemisorption använts för att kvantifiera vilken utsträckning katalysatorn har blivit deaktiverad har resulterat i en reproducerbarhet på 17%. Denna studie har syftat till att minska detta, men även till att utföra prestandamätningar för att se om det existerar korrelationer mellan dispersion och tändtemperatur (LOT). Två katalysatorer undersöktes, LLC (lågladdad katalysator) och HLC (högladdad katalysator), både som färska, men även som hydrotermiskt åldrade i 600 C, 700 C and 800 C. Dessutom undersöktes två motorcellsprover av HLC. För att säkerställa provhomogenitet undersöktes olika provprepareringsmetoder. Katalysatorprover krossades, eller fick washcoat avlägsnat eller maldes samt siktades. Totalt fem körningar gjordes på färska katalysatorer (LLC och HLC). Prestandamätningar gjordes på samtliga prov i Synthetic Catalyst Activity Testing (SCAT). Det bedömdes att den enda gångbara provprepareringsmetoden var att mala samt sikta katalysatorn då de andra metoderna skulle bli svåra att upprepa på ett reproducerbart sätt. Resultaten visade att reproducerbarheten för LLC var %STD = 4% och för HLC %STD = 2%. LLC visade på korrelation mellan katalytisk aktivitet och dispersion. Aktiviteten minskade linjärt utan större förluster i BETytarea. För HLC minskade dispersionen i hög grad med ökad åldringstemperatur, däremot kunde ingen korrelation med katalytisk aktivitet påvisas; enbart då katalysatorn åldrades vid 800 C ändrades LOT signifikant. Förändringarna i BET-ytarean var inte beroende av åldringstemperatur då lägre dispersion ibland resulterade i högre ytarea. För motorcellsproverna uppmättes en märkbart låg dispersion, medan ytarean var relativt oförändrad. Dessa resultat kunde inte korreleras till de hydrotermiskt åldrade proverna, vilket kan bero på att andra effekter inhiberat CO kemisorptionen.

Over the years electronic structure theory has proven to be a powerful method with which one can probe the behaviour of materials, making it possible to predict properties that are difficult to measure experimentally. The numerical tools needed for these methods are always in need of development, since the desire to calculate more complex materials pushes this field forward. This thesis contains work on both this implementational and developmental aspects. In the first part we investigate the structural properties of the 6d transition metals using the exact muffin-tin orbitals method. It is found that these elements behave similarly to their lighter counterparts, except for a few deviations. In these cases we argue that it is relativistic effects that cause this anomalous behaviour. In the second part we assess the Padé approximant, which is used in several methods where one wants to include many-body effects into the electronic structure. We point out difficulties that can occur when using this approximant, and propose and evaluate methods for their solution. / <p>QC 20130219</p>

No description available.

It is sometimes said that money speaks louder than words, and in a world where financial decisions are a major driving force, it is interesting to explore how monetary incentives influence our decision making. Some argue that intrinsic motivation is sufficient to be able to measure prosocial decision-making, but what happens when we add monetary incentives to experiments that might otherwise be conducted with hypothetical scenarios? In this study, we conduct an online experiment with 1002 participants to explore if decision making changes when monetary incentives are introduced. The experiment includes five different social dilemmas involving distributions of money between participants. There are two conditions where one group makes hypothetical decisions and the other group receives money based on their decisions (i.e., is incentivized). Furthermore, we investigate if income, age and gender affect prosocial behavior. Our results suggest that both conditions show similar effects on prosocial behavior which implies that usage of either one of the two conditions will generate an equivalent outcome. The effects from household income, age and gender were significant in some social dilemmas, but the effect was not practically relevant for this study. We believe our results may be useful to include in the discussion of whether or not monetary incentives and hypothetical decisions generate similar results when studying prosocial behavior in decision making in experiments.

No description available.

NKT cells are an important part of human immune system and recognize a specific set of antigens called glycolipids. Only a handful of "natural" NKT cell antigens are known till date. Although NKT cells play a protective role against pathogenic organisms, imbalances in NKT cell functions are implicated in many diseases including asthma. Allergic asthma, a Th2 driven inflammation of airways, is primarily caused by inhalation of environmental allergens. In the last decade, inhaled allergen Aspergillus fumigatus has been under scrutiny for the presence of NKT cell antigens that might trigger asthma. We successfully isolated, characterized and synthesized a "natural" antigenic glycolipid which activates NKT cells in CD1d dependent manner. When this glycolipid is administered intranasally to mice, WT but not CD1d-/- mice developed airway hyperreactivity (AHR), which is a cardinal feature of asthma. Our results indicate that this glycolipid also triggers the production of key cytokines responsible for development of airway hyperreactivity, namely IL-4 and IL-13. Widespread use of antibiotics has convoluted the problem of antimicrobial resistance. Our research group has developed a novel class of antimicrobial peptide mimics called Ceragennins. These cholic acid based antimicrobial compounds have many desirable properties including low MICs, effectiveness against biofilms, and relatively low manufacturing cost. In order to advance the clinical development of Ceragennins, we developed analytical methods for qualitative and quantitative determination of these compounds in complex biological matrices. These methods were also used for carrying out the stability studies of Ceragenins under varying pH and temperatures

No description available.

Embargoed until July 2016. / Active Pharmaceutical Ingredients (APIs) are frequently prepared for delivery to the lung for local topical treatment of diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, or for systemic delivery. One of the most commonly used devices for this purpose is the pressurised metered dose inhaler (pMDI) whereby drugs are formulated in a volatile propellant held under pressure. The compound is aerosolised to a respirably sized dose on actuation, subsequently breathed in by the user. The use of hydrofluoroalkanes (HFAs) in pMDIs since the Montreal Protocol initiated a move away from chlorofluorocarbon (CFC) based devices has resulted in better performing products, with increased lung deposition and a concomitant reduction in oropharyngeal deposition. The physical properties of HFA propellants are however poorly understood and their capacity for solubilising inhaled pharmaceutical products (IPPs) and excipients used historically in CFCs differ significantly. There is therefore a drive to establish methodologies to study these systems in-situ and post actuation to adequately direct formulation strategies for the production of stable and efficacious suspension and solution based products. Characterisation methods have been applied to pMDI dosage systems to gain insight into solubility in HFAs and to determine forms of solid deposits after actuation. A novel quantitative nuclear magnetic resonance method to investigate the physical chemistry of IPPs in these preparations has formed the centrepiece to these studies, accessing solubility data in-situ and at pressure for the first time in HFA propellants. Variable temperature NMR has provided thermodynamic data through van’t Hoff approaches. The methods have been developed and validated using budesonide to provide limits of determination as low as 1 μg/mL and extended to 11 IPPs chosen to represent currently prescribed inhaled corticosteroids (ICS), β2-adrenoagonists and antimuscarinic bronchodilators, and have highlighted solubility variations between the classes of compounds with lipophilic ICSs showing the highest, and hydrophilic β2- agonist / antimuscarinics showing the lowest solubilities from the compounds under study. To determine solid forms on deposition, a series of methods are also described using modified impaction methods in combination with analytical approaches including spectroscopy (μ-Raman), X-ray diffraction, SEM, chromatography and thermal analysis. Their application has ascertained (i) physical form / morphology data on commercial pMDI formulations of the ICS beclomethasone dipropionate (QVAR® / Sanasthmax®, Chiesi) and (ii) distribution assessment in-vitro of ICS / β2-agonist compounds from combination pMDIs confirming co-deposition (Seretide® / Symbicort®, GlaxoSmithKline / AstraZeneca). In combination, these methods provide a platform for development of new formulations based on HFA propellants. The methods have been applied to a number of ‘real’ systems incorporating derivatised cyclodextrins and the co-solvent ethanol, and provide a basis for a comprehensive study of solubilisation of the ICS budesonide in HFA134a using two approaches: mixed solvents and complexation. These new systems provide a novel approach to deliver to the lung, with reduced aerodynamic particle size distribution (APSD) potentially accessing areas suitable for delivery to peripheral areas of the lung (ICS) or to promote systemic delivery.

No description available.