The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a_2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A_2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A_2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.

Biopolttoaineiden lisäämismahdollisuudet kaukolämmön tuotannossa pienen kokoluokan tuotantolaitoksissa Lahden seudulla

Tämä diplomityö on tehty IMMU-hankkeeseen, jossa selvitetään konkreettisia keinoja ilmastonmuutoksen hillintään Lahden seudulla. Diplomityössä tarkastellaan mahdollisuuksia lisätä biopolttoaineita pienen kokoluokan kaukolämmön tuotantolaitoksissa. Teoria osuuden pohjalta luodaan skenaariot Nastolaan ja Vääksyyn (Asikkala). Skenaarioissa tarkastellaan biopolttoaineiden lisäämisen vaikutuksia kasvihuonekaasu- ja hiukkaspäästöihin käyttämällä elinkaariarviointimenetelmää. Taloudellisia seikkoja tarkastellaan laskemalla takaisinmaksuaikoja eri biolaitosratkaisuille nettonykyarvomenetelmällä. Tutkimuksen tuloksena saatiin, että kasvihuonekaasupäästöt tuotannon elinkaaren ajalta vähenevät eniten tuottamalla kaukolämmön perustuotanto Nastolassa ja Vääksyssä bio-CHP-laitoksella haketta polttamalla. Kiinteitä biopolttoaineita poltettaessa tulevat kuitenkin suurimmat hiukkaspäästöt, mikä vaikuttaa asuinympäristön viihtyvyyteen tuotantolaitoksen läheisyydessä. Bio-CHP-laitoksen investointikustannukset ovat suurimmat ja takaisinmaksuaika pisin. Nastolan kulutusperusteisiä päästöjä pystytään vähentämään eniten investoimalla biolämpölaitokseen tai bio-CHP-laitokseen. Päästöjä Nastolassa pystyttäisiin kyseisillä investoinneilla vähentämään enimmillään 6,4 %. Lahti energian kokonaispäästöjä pystyttäisiin enimmillään vähentämään noin 1,6 %. Johtopäätöksenä tutkimuksesta voidaan sanoa, että kasvihuonekaasupäästöjä pystytään vähentämään investointien avulla. Toiset ratkaisut ovat vain kalliimpia kuin toiset. Lisäksi kiinteitä biopolttoaineita käytettäessä jotkut poltto-ominaisuudet voivat heiketä esim. verrattuna maakaasun polttoon. Biopolttoaineiden lisäämisellä kuitenkin päästään irti riippuvuudesta fossiilisiin polttoaineisiin kuten öljyyn ja maakaasuun. Investointeja tehdessä on vaikea sanoa suoraan, mikä vaihtoehto on paras tapa tuottaa kaukolämpöä. Investointipäätöksiä tehdessä päätökseen vaikuttaa se, mitä tuotannon ominaispiirteitä painotetaan eniten.

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Time-Resolved Photoluminescence in Antimonide and Dilute Nitride Quantum Well Structures

This Master's thesis is devoted to semiconductor samples study using time-resolved photoluminescence. This method allows investigating recombination in semiconductor samples in order to develop quality of optoelectronic device. An additional goal was the method accommodation for low-energy-gap materials. The first chapter gives a brief intercourse into the basis of semiconductor physics. The key features of the investigated structures are noted. The usage area of the results covers saturable semiconductor absorber mirrors, disk lasers and vertical-external-cavity surface-emittinglasers. The experiment set-up is described in the second chapter. It is based on up-conversion procedure using a nonlinear crystal and involving the photoluminescent emission and the gate pulses. The limitation of the method was estimated. The first series of studied samples were grown at various temperatures and they suffered rapid thermal annealing. Further, a latticematched and metamorphically grown samples were compared. Time-resolved photoluminescence method was adapted for wavelengths up to 1.5 µm. The results allowed to specify the optimal substrate temperature for MBE process. It was found that the lattice-matched sample and the metamorphically grown sample had similar characteristics.

Optimization of wind blade design including its energetic characteristics

The goal of the Master’s thesis is to develop and to analyze the optimization method for finding a geometry shape of classical horizontal wind turbine blades based on set of criteria. The thesis develops a technique that allows the designer to determine the weight of such factors as power coefficient, sound pressure level and the cost function in the overall process of blade shape optimization. The optimization technique applies the Desirability function. It was never used before in that kind of technical problems, and in this sense it can claim to originality of research. To do the analysis and the optimization processes more convenient the software application was developed.

Solution marketing characteristics and practices

The first objective of this master's thesis is to find out how the concepts solution and solution marketing are defined in the literature. In order to do so, solution marketing literature is reviewed widely. Another target is to identify the characteristics of solution marketing and to explain how solution marketing can be carried out. The final objective is to determine how well the described solution marketing practices are executed in the target company, and this will be studied with a survey. A solution can be described as a co-created and customized combination of products and services. Solution marketing aims at developing and anticipating customer's business needs and it involves close collaboration between customer and supplier. Solution marketing communication is targeted to a specific audience. It entails deep customer intimacy and is focused on understanding customer's business problem. Solution marketing also requires close collaboration between sales and marketing as well as customer focused mindset. Solution marketing can be executed by promoting thought leadership, presenting solution offering, creating close customer relationships and treating customers as individuals. Solution provider's whole organization must engage customer focus.

The Effects of Some Furnish and Paper Structure Related Factors on Wet Web Tensile and Relaxation Characteristics

The objective of this thesis was to identify the effects of different factors on the tension and tension relaxation of wet paper web after high-speed straining. The study was motivated by the plausible connection between wet web mechanical properties and wet web runnability on paper machines shown by previous studies. The mechanical properties of wet paper were examined using a fast tensile test rig with a strain rate of 1000%/s. Most of the tests were carried out with laboratory handsheets, but samples from a pilot paper machine were also used. The tension relaxation of paper was evaluated as the tension remaining after 0.475 s of relaxation (residual tension). The tensile and relaxation properties of wet webs were found to be strongly dependent on the quality and amount of fines. With low fines content, the tensile strength and residual tension of wet paper was mainly determined by the mechanical interactions between fibres at their contact points. As the fines strengthen the mechanical interaction in the network, the fibre properties also become important. Fibre deformations caused by the mechanical treatment of pulp were shown to reduce the mechanical properties of both dry and wet paper. However, the effect was significantly higher for wet paper. An increase of filler content from 10% to 25% greatly reduced the tensile strength of dry paper, but did not significantly impair wet web tensile strength or residual tension. Increased filler content in wet web was shown to increase the dryness of the wet web after the press section, which partly compensates for the reduction of fibrous material in the web. It is also presumable that fillers increase entanglement friction between fibres, which is beneficial for wet web strength. Different contaminants present in white water during sheet formation resulted in lowered surface tension and increased dryness after wet pressing. The addition of different contaminants reduced the tensile strength of the dry paper. The reduction of dry paper tensile strength could not be explained by the reduced surface tension, but rather on the tendency of different contaminants to interfere with the inter-fibre bonding. Additionally, wet web strength was not affected by the changes in the surface tension of white water or possible changes in the hydrophilicity of fibres caused by the addition of different contaminants. The spraying of different polymers on wet paper before wet pressing had a significant effect on both dry and wet web tensile strength, whereas wet web elastic modulus and residual tension were basically not affected. We suggest that the increase of dry and wet paper strength could be affected by the molecular level interactions between these chemicals and fibres. The most significant increases in dry and wet paper strength were achieved with a dual application of anionic and cationic polymers. Furthermore, selectively adding papermaking chemicals to different fibre fractions (as opposed to adding chemicals to the whole pulp) improved the wet web mechanical properties and the drainage of the pulp suspension.

Akustisen emission anturin signaalin esikäsittelypiirin selvittäminen ja prototyypin toteuttaminen

Tämän työn tavoitteena oli selvittää ja toteuttaa esikäsittelypiirin prototyyppi akustisen emission anturin signaalille. Toteutettu esikäsittelypiiri toimii yksipuoleisella käyttöjännitteellä. Työssä käydään läpi esikäsittelypiirin suunnitteluun liittyvät vaiheet laskelmien ja simulaatioiden muodossa. Lisäksi työssä esitetään mittaustulokset esikäsittelypiirin toiminnasta.

A study of combustion phenomena in circulating fluidized beds by developing and applying experimental and modelling methods for laboratory-scale reactors

The results shown in this thesis are based on selected publications of the 2000s decade. The work was carried out in several national and EC funded public research projects and in close cooperation with industrial partners. The main objective of the thesis was to study and quantify the most important phenomena of circulating fluidized bed combustors by developing and applying proper experimental and modelling methods using laboratory scale equipments. An understanding of the phenomena plays an essential role in the development of combustion and emission performance, and the availability and controls of CFB boilers. Experimental procedures to study fuel combustion behaviour under CFB conditions are presented in the thesis. Steady state and dynamic measurements under well controlled conditions were carried out to produce the data needed for the development of high efficiency, utility scale CFB technology. The importance of combustion control and furnace dynamics is emphasized when CFB boilers are scaled up with a once through steam cycle. Qualitative information on fuel combustion characteristics was obtained directly by comparing flue gas oxygen responses during the impulse change experiments with fuel feed. A one-dimensional, time dependent model was developed to analyse the measurement data Emission formation was studied combined with fuel combustion behaviour. Correlations were developed for NO, N2O, CO and char loading, as a function of temperature and oxygen concentration in the bed area. An online method to characterize char loading under CFB conditions was developed and validated with the pilot scale CFB tests. Finally, a new method to control air and fuel feeds in CFB combustion was introduced. The method is based on models and an analysis of the fluctuation of the flue gas oxygen concentration. The effect of high oxygen concentrations on fuel combustion behaviour was also studied to evaluate the potential of CFB boilers to apply oxygenfiring technology to CCS. In future studies, it will be necessary to go through the whole scale up chain from laboratory phenomena devices through pilot scale test rigs to large scale, commercial boilers in order to validate the applicability and scalability of the, results. This thesis shows the chain between the laboratory scale phenomena test rig (bench scale) and the CFB process test rig (pilot). CFB technology has been scaled up successfully from an industrial scale to a utility scale during the last decade. The work shown in the thesis, for its part, has supported the development by producing new detailed information on combustion under CFB conditions.

Characteristics of credit risk assessment methods of major Nordic banks in allocating capital when extending credits to large corporations

Credit risk assessment is an integral part of banking. Credit risk means that the return will not materialise in case the customer fails to fulfil its obligations. Thus a key component of banking is setting acceptance criteria for granting loans. Theoretical part of the study focuses on key components of credit assessment methods of Banks in the literature when extending credits to large corporations. Main component is Basel II Accord, which sets regulatory requirement for credit risk assessment methods of banks. Empirical part comprises, as primary source, analysis of major Nordic banks’ annual reports and risk management reports. As secondary source complimentary interviews were carried out with senior credit risk assessment personnel. The findings indicate that all major Nordic banks are using combination of quantitative and qualitative information in credit risk assessment model when extending credits to large corporations. The relative input of qualitative information depends on the selected approach to the credit rating, i.e. point-in-time or through-the-cycle.

Imaging of Dopamine and Serotonin Transporters. Pre-clinical Studies with Radiotracers for Positron Emission Tomography

The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [¹⁸F]beta -CFT-FP and ¹⁸FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [¹⁸F]beta-CFT, a well known DAT tracer, with a ¹⁸Ffluoropropyl group significantly changed the properties of the tracer. [¹⁸F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [¹⁸F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [¹⁸F]betaCFT-FP was selective for DAT; but [¹⁸F]beta-CFT also bound to the noradrenaline transporter. [¹⁸F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, ¹⁸FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, ¹⁸FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [¹⁸F]beta CFT and [¹⁸ F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [¹⁸F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [¹⁸F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [¹⁸F]-CFT-FP and ¹⁸FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [¹⁸F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.