Monetary Policy, Stock Price Misalignments and Macroeconomic Instability

Perhaps the most fundamental prediction of financial theory is that the expected returns on financial assets are determined by the amount of risk contained in their payoffs. Assets with a riskier payoff pattern should provide higher expected returns than assets that are otherwise similar but provide payoffs that contain less risk. Financial theory also predicts that not all types of risks should be compensated with higher expected returns. It is well-known that the asset-specific risk can be diversified away, whereas the systematic component of risk that affects all assets remains even in large portfolios. Thus, the asset-specific risk that the investor can easily get rid of by diversification should not lead to higher expected returns, and only the shared movement of individual asset returns – the sensitivity of these assets to a set of systematic risk factors – should matter for asset pricing. It is within this framework that this thesis is situated. The first essay proposes a new systematic risk factor, hypothesized to be correlated with changes in investor risk aversion, which manages to explain a large fraction of the return variation in the cross-section of stock returns. The second and third essays investigate the pricing of asset-specific risk, uncorrelated with commonly used risk factors, in the cross-section of stock returns. The three essays mentioned above use stock market data from the U.S. The fourth essay presents a new total return stock market index for the Finnish stock market beginning from the opening of the Helsinki Stock Exchange in 1912 and ending in 1969 when other total return indices become available. Because a total return stock market index for the period prior to 1970 has not been available before, academics and stock market participants have not known the historical return that stock market investors in Finland could have achieved on their investments. The new stock market index presented in essay 4 makes it possible, for the first time, to calculate the historical average return on the Finnish stock market and to conduct further studies that require long time-series of data.

Technical efficiency of blood component preparation in blood centres of 10 European countries

Various reasons, such as ethical issues in maintaining blood resources, growing costs, and strict requirements for safe blood, have increased the pressure for efficient use of resources in blood banking. The competence of blood establishments can be characterized by their ability to predict the volume of blood collection to be able to provide cellular blood components in a timely manner as dictated by hospital demand. The stochastically varying clinical need for platelets (PLTs) sets a specific challenge for balancing supply with requests. Labour has been proven a primary cost-driver and should be managed efficiently. International comparisons of blood banking could recognize inefficiencies and allow reallocation of resources. Seventeen blood centres from 10 countries in continental Europe, Great Britain, and Scandinavia participated in this study. The centres were national institutes (5), parts of the local Red Cross organisation (5), or integrated into university hospitals (7). This study focused on the departments of blood component preparation of the centres. The data were obtained retrospectively by computerized questionnaires completed via Internet for the years 2000-2002. The data were used in four original articles (numbered I through IV) that form the basis of this thesis. Non-parametric data envelopment analysis (DEA, II-IV) was applied to evaluate and compare the relative efficiency of blood component preparation. Several models were created using different input and output combinations. The focus of comparisons was on the technical efficiency (II-III) and the labour efficiency (I, IV). An empirical cost model was tested to evaluate the cost efficiency (IV). Purchasing power parities (PPP, IV) were used to adjust the costs of the working hours and to make the costs comparable among countries. The total annual number of whole blood (WB) collections varied from 8,880 to 290,352 in the centres (I). Significant variation was also observed in the annual volume of produced red blood cells (RBCs) and PLTs. The annual number of PLTs produced by any method varied from 2,788 to 104,622 units. In 2002, 73% of all PLTs were produced by the buffy coat (BC) method, 23% by aphaeresis and 4% by the platelet-rich plasma (PRP) method. The annual discard rate of PLTs varied from 3.9% to 31%. The mean discard rate (13%) remained in the same range throughout the study period and demonstrated similar levels and variation in 2003-2004 according to a specific follow-up question (14%, range 3.8%-24%). The annual PLT discard rates were, to some extent, associated with production volumes. The mean RBC discard rate was 4.5% (range 0.2%-7.7%). Technical efficiency showed marked variation (median 60%, range 41%-100%) among the centres (II). Compared to the efficient departments, the inefficient departments used excess labour resources (and probably) production equipment to produce RBCs and PLTs. Technical efficiency tended to be higher when the (theoretical) proportion of lost WB collections (total RBC+PLT loss) from all collections was low (III). The labour efficiency varied remarkably, from 25% to 100% (median 47%) when working hours were the only input (IV). Using the estimated total costs as the input (cost efficiency) revealed an even greater variation (13%-100%) and overall lower efficiency level compared to labour only as the input. In cost efficiency only, the savings potential (observed inefficiency) was more than 50% in 10 departments, whereas labour and cost savings potentials were both more than 50% in six departments. The association between department size and efficiency (scale efficiency) could not be verified statistically in the small sample. In conclusion, international evaluation of the technical efficiency in component preparation departments revealed remarkable variation. A suboptimal combination of manpower and production output levels was the major cause of inefficiency, and the efficiency did not directly relate to production volume. Evaluation of the reasons for discarding components may offer a novel approach to study efficiency. DEA was proven applicable in analyses including various factors as inputs and outputs. This study suggests that analytical models can be developed to serve as indicators of technical efficiency and promote improvements in the management of limited resources. The work also demonstrates the importance of integrating efficiency analysis into international comparisons of blood banking.

Preparation, structural analysis and prebiotic potential of arabinoxylo-oligosaccharides

Arabinoxylo-oligosaccharides (AXOS) can be prepared enzymatically from arabinoxylans (AX) and AXOS are known to possess prebiotic potential. Here the structural features of 10 cereal AX were examined. AX were hydrolysed by Shearzyme® to prepare AXOS, and their structures were fully analysed. The prebiotic potential of the purified AXOS was studied in the fermentation experiments with bifidobacteria and faecal microbiota. In AX extracted from flours and bran, high amounts of a-L-Araf units are attached to the b-D-Xylp main chain, whereas moderate or low degree of substitution was found from husks, cob and straw. Nuclear magnetic resonance (NMR) spectroscopy showed that flour and bran AX contain high amounts of a-L-Araf units bound to the O-3 of b-D-Xylp residues and doubly substituted b-D-Xylp units with a-L-Araf substituents at O-2 and O-3. Barley husk and corn cob AX contain high amounts of b-D-Xylp(1→2)-a-L-Araf(1→3) side chains, which can also be found in AX from oat spelts and rice husks, and in lesser amounts in wheat straw AX. Rye and wheat flour AX and oat spelt AX were hydrolysed by Shearzyme® (with Aspergillus aculeatus GH10 endo-1,4-b-D-xylanase as the main enzyme) for the production of AXOS on a milligram scale. The AXOS were purified and their structures fully analysed, using mass spectrometry (MS) and 1D and 2D NMR spectroscopy. Monosubstituted xylobiose and xylotriose with a-L-Araf attached to the O-3 or O-2 of the nonreducing end b-D-Xylp unit and disubstituted AXOS with two a-L-Araf units at the nonreducing end b-D-Xylp unit of xylobiose or xylotriose were produced. Xylobiose with b-D-Xylp(1→2)-a-L-Araf(1→3) side chain was also purified. These AXOS were used as standards in further identification and quantification of corresponding AXOS from the hydrolysates in high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) analysis. The prebiotic potential of AXOS was tested in in vitro fermentation experiments. Bifidobacterium adolescentis ATCC 15703 and B. longum ATCC 15707 utilized AXOS from the AX hydrolysates. Both species released L-arabinose from AXOS, but B. adolescentis consumed the XOS formed, whereas B. longum fermented the L-arabinose released. The third species tested, B. breve ATCC 15700, grew poorly on these substrates. When cultivated on pure AXOS, the bifidobacterial mixture utilized pure singly substituted AXOS almost completely, but no growth was detected with pure doubly substituted AXOS as substrates. However, doubly substituted AXOS were utilized from the mixture of xylose, XOS and AXOS. Faecal microbiota utilized both pure singly and doubly substituted AXOS. Thus, a mixture of singly and doubly substituted AXOS could function as a suitable, slowly fermenting prebiotic substance. This thesis contributes to the structural information on cereal AX and preparation of mono and doubly substituted AXOS from AX. Understanding the utilization strategies is fundamental in evaluating the prebiotic potential of AXOS. Further research is still required before AXOS can be used in applications for human consumption.

Use of non-specific and specific interactions in the analysis of testosterone and related compounds by capillary electromigration techniques

Determination of testosterone and related compounds in body fluids is of utmost importance in doping control and the diagnosis of many diseases. Capillary electromigration techniques are a relatively new approach for steroid research. Owing to their electrical neutrality, however, separation of steroids by capillary electromigration techniques requires the use of charged electrolyte additives that interact with the steroids either specifically or non-specifically. The analysis of testosterone and related steroids by non-specific micellar electrokinetic chromatography (MEKC) was investigated in this study. The partial filling (PF) technique was employed, being suitable for detection by both ultraviolet spectrophotometry (UV) and electrospray ionization mass spectrometry (ESI-MS). Efficient, quantitative PF-MEKC UV methods for steroid standards were developed through the use of optimized pseudostationary phases comprising surfactants and cyclodextrins. PF-MEKC UV proved to be a more sensitive, efficient and repeatable method for the steroids than PF-MEKC ESI-MS. It was discovered that in PF-MEKC analyses of electrically neutral steroids, ESI-MS interfacing sets significant limitations not only on the chemistry affecting the ionization and detection processes, but also on the separation. The new PF-MEKC UV method was successfully employed in the determination of testosterone in male urine samples after microscale immunoaffinity solid-phase extraction (IA-SPE). The IA-SPE method, relying on specific interactions between testosterone and a recombinant anti-testosterone Fab fragment, is the first such method described for testosterone. Finally, new data for interactions between steroids and human and bovine serum albumins were obtained through the use of affinity capillary electrophoresis. A new algorithm for the calculation of association constants between proteins and neutral ligands is introduced.

Functional genes and gene array analysis as tools for monitoring hydrocarbon biodegradation

Bioremediation, which is the exploitation of the intrinsic ability of environmental microbes to degrade and remove harmful compounds from nature, is considered to be an environmentally sustainable and cost-effective means for environmental clean-up. However, a comprehensive understanding of the biodegradation potential of microbial communities and their response to decontamination measures is required for the effective management of bioremediation processes. In this thesis, the potential to use hydrocarbon-degradative genes as indicators of aerobic hydrocarbon biodegradation was investigated. Small-scale functional gene macro- and microarrays targeting aliphatic, monoaromatic and low molecular weight polyaromatic hydrocarbon biodegradation were developed in order to simultaneously monitor the biodegradation of mixtures of hydrocarbons. The validity of the array analysis in monitoring hydrocarbon biodegradation was evaluated in microcosm studies and field-scale bioremediation processes by comparing the hybridization signal intensities to hydrocarbon mineralization, real-time polymerase chain reaction (PCR), dot blot hybridization and both chemical and microbiological monitoring data. The results obtained by real-time PCR, dot blot hybridization and gene array analysis were in good agreement with hydrocarbon biodegradation in laboratory-scale microcosms. Mineralization of several hydrocarbons could be monitored simultaneously using gene array analysis. In the field-scale bioremediation processes, the detection and enumeration of hydrocarbon-degradative genes provided important additional information for process optimization and design. In creosote-contaminated groundwater, gene array analysis demonstrated that the aerobic biodegradation potential that was present at the site, but restrained under the oxygen-limited conditions, could be successfully stimulated with aeration and nutrient infiltration. During ex situ bioremediation of diesel oil- and lubrication oil-contaminated soil, the functional gene array analysis revealed inefficient hydrocarbon biodegradation, caused by poor aeration during composting. The functional gene array specifically detected upper and lower biodegradation pathways required for complete mineralization of hydrocarbons. Bacteria representing 1 % of the microbial community could be detected without prior PCR amplification. Molecular biological monitoring methods based on functional genes provide powerful tools for the development of more efficient remediation processes. The parallel detection of several functional genes using functional gene array analysis is an especially promising tool for monitoring the biodegradation of mixtures of hydrocarbons.

Transcriptome and proteome analysis of xylose-metabolising Saccharomyces cerevisiae

Increasing concern about global climate warming has accelerated research into renewable energy sources that could replace fossil petroleum-based fuels and materials. Bioethanol production from cellulosic biomass by fermentation with baker s yeast Saccharomyces cerevisiae is one of the most studied areas in this field. The focus has been on metabolic engineering of S. cerevisiae for utilisation of the pentose sugars, in particular D-xylose that is abundant in the hemicellulose fraction of biomass. Introduction of a heterologous xylose-utilisation pathway into S. cerevisiae enables xylose fermentation, but ethanol yield and productivity do not reach the theoretical level. In the present study, transcription, proteome and metabolic flux analyses of recombinant xylose-utilising S. cerevisiae expressing the genes encoding xylose reductase (XR) and xylitol dehydrogenase (XDH) from Pichia stipitis and the endogenous xylulokinase were carried out to characterise the global cellular responses to metabolism of xylose. The aim of these studies was to find novel ways to engineer cells for improved xylose fermentation. The analyses were carried out from cells grown on xylose and glucose both in batch and chemostat cultures. A particularly interesting observation was that several proteins had post-translationally modified forms with different abundance in cells grown on xylose and glucose. Hexokinase 2, glucokinase and both enolase isoenzymes 1 and 2 were phosphorylated differently on the two different carbon sources studied. This suggests that phosphorylation of glycolytic enzymes may be a yet poorly understood means to modulate their activity or function. The results also showed that metabolism of xylose affected the gene expression and abundance of proteins in pathways leading to acetyl-CoA synthesis and altered the metabolic fluxes in these pathways. Additionally, the analyses showed increased expression and abundance of several other genes and proteins involved in cellular redox reactions (e.g. aldo-ketoreductase Gcy1p and 6-phosphogluconate dehydrogenase) in cells grown on xylose. Metabolic flux analysis indicated increased NADPH-generating flux through the oxidative part of the pentose phosphate pathway in cells grown on xylose. The most importantly, results indicated that xylose was not able to repress to the same extent as glucose the genes of the tricarboxylic acid and glyoxylate cycles, gluconeogenesis and some other genes involved in the metabolism of respiratory carbon sources. This suggests that xylose is not recognised as a fully fermentative carbon source by the recombinant S. cerevisiae that may be one of the major reasons for the suboptimal fermentation of xylose. The regulatory network for carbon source recognition and catabolite repression is complex and its functions are only partly known. Consequently, multiple genetic modifications and also random approaches would probably be required if these pathways were to be modified for further improvement of xylose fermentation by recombinant S. cerevisiae strains.

Functional Surfaces for Microfluidics in Proteomic Analysis

Microchips for use in biomolecular analysis show a lot of promise for medical diagnostics and biomedical basic research. Among the potential advantages are more sensitive and faster analyses as well as reduced cost and sample consumption. Due to scaling laws, the surface are to volume ratios of microfluidic chips is very high. Because of this, tailoring the surface properties and surface functionalization are very important technical issues for microchip development. This thesis studies two different types of functional surfaces, surfaces for open surface capillary microfluidics and surfaces for surface assisted laser desorption ionization mass spectrometry, and combinations thereof. Open surface capillary microfluidics can be used to transport and control liquid samples on easily accessible open surfaces simply based on surface forces, without any connections to pumps or electrical power sources. Capillary filling of open partially wetting grooves is shown to be possible with certain geometries, aspect ratios and contact angles, and a theoretical model is developed to identify complete channel filling domains, as well as partial filling domains. On the other hand, partially wetting surfaces with triangular microstructures can be used for achieving directional wetting, where the water droplets do not spread isotropically, but instead only spread to a predetermined sector. Furthermore, by patterning completely wetting and superhydrophobic areas on the same surface, complex droplet shapes are achieved, as the water stretches to make contact with the wetting surface, but does not enter into the superhydrophobic domains. Surfaces for surface assisted laser desorption ionization mass spectrometry are developed by applying various active thin film coatings on multiple substrates, in order to separate surface and bulk effects. Clear differences are observed between both surface and substrate layers. The best performance surfaces consisted of amorphous silicon coating and an inorganic-organic hybrid substrate, with nanopillars and nanopores. These surfaces are used for matrix-free ionization of drugs, peptides and proteins, and for some analytes, the detection limits were in the high attomoles. Microfluidics and laser desorption ionization surfaces are combined on a functionalized drying platforms, where the surface is used to control the shape of the deposited analyte droplet, and the shape of the initial analyte droplet affects the dried droplet solute deposition pattern. The deposited droplets can then directly detected by mass spectrometry. Utilizing this approach, results of analyte concentration, splitting and separation are demonstrated.