Helsingin Östersundomin pienvesien kartoitus

The area of Östersundom (29,1 square kilometers) was attached to Helsinki in the beginning of the year 2009. Östersundom is formed mostly from the municipality of Sipoo, and partly from the city of Vantaa. Nowadays Östersundom is still quite rural, but city planning has already started, and there are plans to develop Östersundom into a district with 45 000 inhabitants. In this study, the headwaters, streams and small lakes of Östersundom were studied to produce information as a basis for city planning. There are six main streams and five small lakes in Östersundom. The main methodology used in this study was the examination of the physical and the chemical quality of the water. The hygienic quality of the water was also studied. It was also examined whether the waters are in their natural state, or have they been treated and transformed by man. In addition, other factors affecting the waters were examined. Geographical information data was produced as a result of this work. Östersundom is the main area looked at in this study, some factors are examined in the scope of the catchment areas. Water samples were collected in three sampling periods: 31.8 4.9.2009, 3. 4.2.2010, and 10. 14.4.2010. There were 20 sampling points in Östersundom (5 in small lakes, 15 in streams). In the winter sampling period, only six samples were collected, from which one was taken from a small lake. Field measurements associated with water sampling included water temperature, oxygen concentration, pH and electoral conductivity. Water samples were analyzed in the Laboratories of Physical Geography in the University of Helsinki for the following properties: total suspended solids (TSS), total dissolved substances (TDS), organic matter, alkalinity, colour, principal anions and cations and trace elements. Metropolilab analyzed the amount of faecal coliform bacteria in the samples. The waters in Östersundom can be divided to three classes according to water quality and other characteristics: the upper course of the streams, the lower course of the streams and the small lakes. The streams in their upper course are in general acidic, and their acid neutralization capacity is low. The proportion of the organic matter is high. Also the concentrations of aluminium and iron tend to be high. The streams in the lower course have acidity closer to neutral, and the buffering capacity is good. The amounts of TSS and TDS are high, and as a result, the concentrations of many ions and trace elements are high as well. Bacteria were detected at times in the streams of the lower course. Four of the five small lakes in Östersundom are humic and acidic. TSS and TDS concentrations tend to be low, but the proportion of organic matter is often high. There were no bacteria in the small lakes. The fifth small lake (Landbonlampi) differs from the others by its water colour, which is very clear. This lake is very acidic, and its buffering capacity is extremely low. Compared to the headwaters in Finland in general, the concentrations of many ions and trace elements are higher in Östersundom. On the other hand, the characteristics of water were different according to the classification upper course streams, lower course streams, and small lakes. Generally, the best water quality was observed in the stream of Gumbölenpuro and in the lakes Storträsk, Genaträsk, Hältingträsk and Landbonlampi. Several valuable waters in their natural state were discovered from the area. The most representative example is the stream of Östersundominpuro in its lower course, where the stream flows through a broad-leaf forest area. The small lakes of Östersundom, and the biggest stream Krapuoja, with its meandering channel, are also valuable in their natural state.

Teknillistaloudellinen tutkimus vesisäiliöistä

Engineering economics study on water tanks and towers.

Maa- ja metsätalouden torjunta-aineiden käytöstä Suomessa ja tärkeimpien yhdisteryhmien vaikutuksista vesissä

The use of pesticides in agricultute and forestry in Finland and the effects of the most important groups in waters.

Towards Understanding Powder Behavior Via Simulation

The aim of this study was to investigate powder and tablet behavior at the level of mechanical interactions between single particles. Various aspects of powder packing, mixing, compression, and bond formation were examined with the aid of computer simulations. The packing and mixing simulations were based on spring forces interacting between particles. Packing and breakage simulations included systems in which permanent bonds were formed and broken between particles, based on their interaction strengths. During the process, a new simulation environment based on Newtonian mechanics and elementary interactions between the particles was created, and a new method for evaluating mixing was developed. Powder behavior is a complicated process, and many of its aspects are still unclear. Powders as a whole exhibit some aspects of solids and others of liquids. Therefore, their physics is far from clear. However, using relatively simple models based on particle-particle interaction, many powder properties could be replicated during this work. Simulated packing densities were similar to values reported in the literature. The method developed for describing powder mixing correlated well with previous methods. The new method can be applied to determine mixing in completely homogeneous materials, without dividing them into different components. As such, it can describe the efficiency of the mixing method, regardless of the powder's initial setup. The mixing efficiency at different vibrations was examined, and we found that certain combinations of amplitude, direction, and frequencies resulted in better mixing while using less energy. Simulations using exponential force potentials between particles were able to explain the elementary compression behavior of tablets, and create force distributions that were similar to the pressure distributions reported in the literature. Tablet-breaking simulations resulted in breaking strengths that were similar to measured tablet breaking strengths. In general, many aspects of powder behavior can be explained with mechanical interactions at the particle level, and single particle properties can be reliably linked to powder behavior with accurate simulations.

Onnellisten kylät : Vertaileva tapaustutkimus Kumpulan ja Sundsbergin asukkaiden subjektiivisesta hyvinvoinnista sekä onnellisuuden rakentumisesta

The aim of this masters thesis was to examine subjective wellbeing and personal happiness. Empirical study of happiness is part of broader wellbeing reseach and is based on an idea that the best experts of personal wellbeing are the individuals themselves. In addition to perceptions of personal happiness, the aim was also to acquire knowledge about personal values and components personal happiness is based on. In this study, moving into certain community and the charesteristics of neigbourhood contributing happiness, were defined to represent these values. The object was, through comparative casestudy, to obtain knowledge about subjective wellbeing of the inviduals in two different residental areas inside metropolitan area of Helsinki. In comparative case study the intention usually is that the examined units represent spesific "cases" from something broader and therefore the results can be somehow generalized. Consequently the chosen cases in this study were selected due to their image of "urban village" and thus the juxtapositioning was constructed between secluded post-suburban village and more heterogeneous urban village better attached to excisting urban structure. The researh questins were formed as follows: Are there any differencies between the areas regarding the components personal happines is based on? Are there any differencies between the areas regarding the level of residents subjective wellbeing? Based on the residents assesments, what are the most important charesteristics of neigbourhood contributing personal happiness? The data used in order to gain aswers to these questions was obtained from internet-based survey questionnaire. Based on the data residents of post-suburban village Sundsberg seem to share highly family oriented set of values and actualizing these values is ensured with high income, wealth and secure work situation. Insteadt in Kumpula the components of happiness seem place more towards learning and personal developement, interesting leisure and hobbies and specially having an influence regarding communal decisions. Conserning subjective wellbeing of residents there can be seen some differencies as well. Personal life is experienced a bit more happier in Sundsberg than in Kumpula. People are more satified with their personal health and job satisfaction in Sundsberg and additionally feelings of loneliness, inadequancy and frustration are bit more common in Kumpula. Regarding the charesteristics of neigbourhood contributing happiness data suggests that key charesteristics of area are peacefulness and safely, good location and connections and proximity of parks and recreational areas. These charesteristics were concidered highly significant in both areas but they were experienced to actualize better in Kumpula. In addition to these components the residents in Kumpula were overall more satisfied with various charecteristics contiburing happiness in their residental area. Besides these attributes mentioned above residents in Kumpula emphasize also some "softer" elements connecting into social, functional and communal side of area. From Sundsberg point of view residental area best contributing happiness is child friendly and safe community based on likeminded people who share the same sosioeconomical situation. The results of this study can be linked back into the society and metropolitan area, which they were chosen from as a cases to be studied. The results can thereby be seen as an example of differentation of conditions of personal happiness between certain population segments. It is possible to detect an spatial dimetion to this process as well and thereby the results suggests that regional segmentation affects between high-ranking residental areas as well. Thereby the results of this reseach contributes to the debate on innovative, diverse and dynamic urban area and as well cohesion of metropolitan area and the society in whole.

Mesoporous silica- and silicon-based materials as carriers for poorly water soluble drugs

New chemical entities with unfavorable water solubility properties are continuously emerging in drug discovery. Without pharmaceutical manipulations inefficient concentrations of these drugs in the systemic circulation are probable. Typically, in order to be absorbed from the gastrointestinal tract, the drug has to be dissolved. Several methods have been developed to improve the dissolution of poorly soluble drugs. In this study, the applicability of different types of mesoporous (pore diameters between 2 and 50 nm) silicon- and silica-based materials as pharmaceutical carriers for poorly water soluble drugs was evaluated. Thermally oxidized and carbonized mesoporous silicon materials, ordered mesoporous silicas MCM-41 and SBA-15, and non-treated mesoporous silicon and silica gel were assessed in the experiments. The characteristic properties of these materials are the narrow pore diameters and the large surface areas up to over 900 m²/g. Loading of poorly water soluble drugs into these pores restricts their crystallization, and thus, improves drug dissolution from the materials as compared to the bulk drug molecules. In addition, the wide surface area provides possibilities for interactions between the loaded substance and the carrier particle, allowing the stabilization of the system. Ibuprofen, indomethacin and furosemide were selected as poorly soluble model drugs in this study. Their solubilities are strongly pH-dependent and the poorest (< 100 µg/ml) at low pH values. The pharmaceutical performance of the studied materials was evaluated by several methods. In this work, drug loading was performed successfully using rotavapor and fluid bed equipment in a larger scale and in a more efficient manner than with the commonly used immersion methods. It was shown that several carrier particle properties, in particular the pore diameter, affect the loading efficiency (typically ~25-40 w-%) and the release rate of the drug from the mesoporous carriers. A wide pore diameter provided easier loading and faster release of the drug. The ordering and length of the pores also affected the efficiency of the drug diffusion. However, these properties can also compensate the effects of each other. The surface treatment of porous silicon was important in stabilizing the system, as the non-treated mesoporous silicon was easily oxidized at room temperature. Different surface chemical treatments changed the hydrophilicity of the porous silicon materials and also the potential interactions between the loaded drug and the particle, which further affected the drug release properties. In all of the studies, it was demonstrated that loading into mesoporous silicon and silica materials improved the dissolution of the poorly soluble drugs as compared to the corresponding bulk compounds (e.g. after 30 min ~2-7 times more drug was dissolved depending on the materials). The release profile of the loaded substances remained similar also after 3 months of storage at 30°C/56% RH. The thermally carbonized mesoporous silicon did not compromise the Caco-2 monolayer integrity in the permeation studies and improved drug permeability was observed. The loaded mesoporous silica materials were also successfully compressed into tablets without compromising their characteristic structural and drug releasing properties. The results of this research indicated that mesoporous silicon/silica-based materials are promising materials to improve the dissolution of poorly water soluble drugs. Their feasibility in pharmaceutical laboratory scale processes was also confirmed in this thesis.

Ksylitolilaatujen käyttö täyteaineena ja niiden puristuminen tabletiksi

Ksylitolilla on edulliset käyttöominaisuudet. Edullisista käyttöominaisuuksista huolimatta ksylitolin käyttö lääkevalmisteiden apuaineena on vähäistä. Viime vuosina lääketeollisuudessa on kuitenkin lisääntynyt kiinnostus ksylitoliin ja muihin sokerialkoholeihin. Kirjallisuudesta löytyy vain vähän tietoa ksylitolin puristuvuudesta ja sen soveltuvuudesta tablettien täyteaineeksi. Tässä työssä karakterisoitiin erilaisten ksylitolilaatujen ominaisuuksia ja niiden soveltuvuutta suorapuristuksella valmistettavien tablettien täyteaineeksi. Materiaaleina käytettiin kolmea rakeistettua ksylitolia ja kahta jauhemaista ksylitolia. Ksylitolilaaduista tutkittiin ominaisuudet, joilla on vaikutusta materiaalin puristumiseen. Tutkittavat ominaisuudet olivat kaato- ja tärytiheys, todellinen tiheys, partikkelikoko ja partikkelikokojakauma ja valuvuus. Kirjallisuuden perusteella ksylitoli on lievästi hygroskooppinen, joten tässä työssä tutkittiin myös ksylitolin hygroskooppisuus eri olosuhteissa. Työssä tutkittiin ksylitolin puristuvuutta yksin ja yhdessä huonosti puristuvan lääkeaineen, parasetamolin, kanssa. Eri ksylitolilaatujen puristumista tutkittiin eri-kokoisilla painimilla. Ksylitoli on hyvin soveltuva apuaine myös lapsille tarkoitettuihin lääkevalmisteisiin ja siten tutkittiin myös oliko ksylitolista mahdollista puristaa minitabletteja. Minitablettien käyttö tulevaisuudessa lasten annostelumuotona tulee todennäköisesti lisääntymään. Rakeistetut ksylitolilaadut puristuivat tämän tutkimuksen perusteella suhteellisen hyvin. Jauhemaiset ksylitolit puristuivat huonosti. Syynä näiden huonoon puristuvuuteen oli liian suuri partikkelikoko ja partikkelikokojakauma, joka esti partikkelien välisten sidosten muodostumista. Parasetamoli heikensi huomattavasti kaikkien ksylitolilaatujen puristuvuutta. Ksylitoli ei siis yksinään pysty kumoamaan parasetamolin huonoa puristuvuutta, vaan formulaatioon tarvittaisiin ksylitolin lisäksi jokin yleisesti tablettien suorapuristuksessa käytettävä täyteaine. Tämän tutkimuksen perusteella ksylitoli on hygroskooppinen, mutta vasta suhteellisen kosteuden ollessa hyvin korkea (95 %). Siten ksylitolin hygroskooppisuus ei ole haitaksi ajatellen ksylitolia sisältävien valmisteiden valmistusta tai säilytystä.

Polarization studies in electromagnetic scattering by small Solar-system particles

In remote-sensing studies, particles that are comparable to the wavelength exhibit characteristic features in electromagnetic scattering, especially in the degree of linear polarization. These features vary with the physical properties of the particles, such as shape, size, refractive index, and orientation. In the thesis, the direct problem of computing the unknown scattered quantities using the known properties of the particles and the incident radiation is solved at both optical and radar spectral regions in a unique way. The internal electromagnetic fields of wavelength-scale particles are analyzed by using both novel and established methods to show how the internal fields are related to the scattered fields in the far zone. This is achieved by using the tools and methods that were developed specifically to reveal the internal field structure of particles and to study the mechanisms that relate the structure to the scattering characteristics of those particles. It is shown that, for spherical particles, the internal field is a combination of a forward propagating wave with the apparent wavelength determined by the refractive index of the particle, and a standing wave pattern with the apparent wavelength the same as for the incident wave. Due to the surface curvature and dielectric nature of the particle, the incident wave front undergoes a phase shift, and the resulting internal wave is focused mostly at the forward part of the particle similar to an optical lens. This focusing is also seen for irregular particles. It is concluded that, for both spherical and nonspherical particles, the interference at the far field between the partial waves that originate from these concentrated areas in the particle interior, is responsible for the specific polarization features that are common for wavelength-scale particles, such as negative values and local extrema in the degree of linear polarization, asymmetry of the phase function, and enhancement of intensity near the backscattering direction. The papers presented in this thesis solve the direct problem for particles with both simple and irregular shapes to demonstrate that these interference mechanisms are common for all dielectric wavelength-scale particles. Furthermore, it is shown that these mechanisms can be applied to both regolith particles in the optical wavelengths and hydrometeors at microwave frequencies. An advantage from this kind of study is that it does not matter whether the observation is active (e.g., polarimetric radar) or passive (e.g., optical telescope). In both cases, the internal field is computed for two mutually perpendicular incident polarizations, so that the polarization characteristics can then be analyzed according to the relation between these fields and the scattered far field.

Konjac- ja galaktoglukomannaanipohjaiset emulsiokalvot

Emulsiokalvolla tarkoitetaan kalvoa, joka on valmistettu haihduttamalla ylimääräinen vesi pois emulsiosta. Polysakkaridipohjainen emulsiokalvo koostuu kalvonmuodostuspolysakkaridista, rasvasta, emulgointiaineesta ja pehmittimestä. Kirjallisuusosassa selvitettiin, mitä raaka-aineita polysakkaridipohjaisissa emulsiokalvoissa käytetään ja mitkä tekijät vaikuttavat emulsiokalvojen vesihöyrynläpäisevyyteen ja mekaanisiin ominaisuuksiin. Tutkimuksen kokeellisen osan tavoitteena oli selvittää, miten konjac-glukomannaani (KGM) ja kuusen galaktoglukomannaani (GGM) soveltuvat emulsiokalvon raaka-aineiksi. Lisäksi selvitettiin, miten rasvan tyyppi ja rasvapitoisuus vaikuttavat GGM-KGM-pohjaisten emulsiokalvojen mekaanisiin ominaisuuksiin ja vesihöyrynläpäisevyyteen. Mehiläisvahasta, mäntyöljystä ja rypsiöljystä valmistettiin emulsiokalvot, joissa oli 30 %:n (paino-% GGM:sta) rasvapitoisuudet. Lisäksi mehiläisvahasta valmistettiin emulsiokalvot, joissa oli 10 ja 50 % mehiläisvahaa. Emulsiokalvoja verrattiin vertailukalvoon, jossa ei ollut rasvaa. Kalvoissa käytetty KGM:n ja GGM:n suhde oli 1:1. Kalvoista mitattiin vesihöyrynläpäisevyys ja -läpäisynopeus, vetolujuus, Youngin moduuli ja murtovenymä. Näiden lisäksi kalvojen poikkileikkaus kuvattiin pyyhkäisyelektronimikroskoopilla. GGM ja KGM soveltuvat emulsiokalvon raaka-aineiksi. Huoneenlämpötilassa kuivatuista kalvoista saatiin tasaisemman näköisiä kuin lämpökaapissa kuivatuista. Pyyhkäisyelektronimikroskooppikuvissa vahapisarat olivat öljypisaroita pienempiä, mikä mahdollisesti vaikutti siihen, että vahapisarat pysyivät paremmin kiinnittyneenä kalvomatriisissa. Öljypisaroiden koko oli kalvoissa noin 10 ?m ja vahapisaroiden 2–6 ?m. Vesihöyrynläpäisynopeus oli pienin 50 %:n mehiläisvahakalvolla (p < 0,05). Vesihöyrynläpäisevyys laski lineaarisesti mehiläisvahapitoisuuden suurentuessa. Öljykalvot ja 10 %:n mehiläisvahakalvo eivät eronneet tilastollisesti merkitsevästi vesihöyrynläpäisevyyden suhteen vertailukalvosta. Pienin vetolujuus ja Youngin moduuli oli 50 %:n mehiläisvahakalvolla. Vertailukalvo oli kestävin ja jäykin. Murtovenymän suhteen kalvot eivät eronneet toisistaan tilastollisesti merkitsevästi. Tutkimuksessa onnistuttiin valmistamaan GGM-KGM-pohjaisia emulsiokalvoja, jotka pidättivät vesihöyryä vertailukalvoa paremmin ja silti säilyttivät mekaaniset ominaisuutensa kohtuullisen hyvin.

Physical properties of a boreal clay soil under differently managed perennial vegetation

The physical properties of surface soil horizons, essentially pore size, shape, continuity and affinity for water, regulate water entry into the soil. These properties are prone to changes caused by natural forces and human activity. The hydraulic properties of the surface soil greatly impact the generation of surface runoff and accompanied erosion, the major concern of agricultural water protection. The general target of this thesis was to improve our understanding of the structural and hydraulic properties of boreal clay soils. Physical properties of a clayey surface soil (0 - 10 cm, clay content 51%), with a micaceous/illitic mineralogy subjected to three different management practices of perennial vegetation, were studied. The study sites were vegetated buffer zones located side by side in SW Finland: 1) natural vegetation with no management, 2) harvested once a year, and 3) grazed by cattle. The soil structure, hydraulic properties, shrinkage properties and soil water repellency were determined at all sites. Two distinct flow domains were evident. The surface soil was characterized by subangular blocky, angular blocky and platy aggregates. Hence, large, partially accommodated, irregular elongated pores dominated the macropore domain at all sites. The intra-aggregate pore system was mostly comprised of pores smaller than 30 μm, which are responsible for water storage. Macropores at the grazed site, compacted by hoof pressure, were horizontally oriented and pore connectivity was poorest, which decreased water and air flux compared with other sites. Drying of the soil greatly altered its structure. The decrease in soil volume between wet and dry soil was 7 - 10%, most of which occurred in the moisture range of field conditions. Structural changes, including irreversible collapse of interaggregate pores, began at matric potentials around -6 kPa indicating, instability of soil structure against increasing hydraulic stress. Water saturation and several freezethaw cycles between autumn and spring likely weakened the soil structure. Soil water repellency was observed at all sites at the time of sampling and when soil was dryer than about 40 vol.%. (matric potential < -6 kPa). Therefore, water repellency contributes to water flow over a wide moisture range. Water repellency was also observed in soils with low organic carbon content (< 2%), which suggests that this phenomenon is common in agricultural soils of Finland due to their relatively high organic carbon content. Aggregate-related pedofeatures of dense infillings described as clay intrusions were found at all sites. The formation of these intrusions was attributed to clay dispersion and/or translocation during spring thaw and drying of the suspension in situ. These processes generate very new aggregates whose physical properties are most probably different from those of the bulk soil aggregates. Formation of the clay infillings suggested that prolonged wetness in autumn and spring impairs soil structure due to clay dispersion, while on the other hand it contributes to the pedogenesis of the soil. The results emphasize the dynamic nature of the physical properties of clay soils, essentially driven by their moisture state. In a dry soil, fast preferential flow is favoured by abundant macropores including shrinkage cracks and is further enhanced by water repellency. Increase in soil moisture reduces water repellency, and swelling of accommodated pores lowers the saturated hydraulic conductivity. Moisture- and temperature-related processes significantly alter soil structure over a time span of 1 yr. Thus, the pore characteristics as well as the hydraulic properties of soil are time-dependent.

Light scattering in random media with wavelength-scale structures : astronomical and industrial applications

Light scattering, or scattering and absorption of electromagnetic waves, is an important tool in all remote-sensing observations. In astronomy, the light scattered or absorbed by a distant object can be the only source of information. In Solar-system studies, the light-scattering methods are employed when interpreting observations of atmosphereless bodies such as asteroids, atmospheres of planets, and cometary or interplanetary dust. Our Earth is constantly monitored from artificial satellites at different wavelengths. With remote sensing of Earth the light-scattering methods are not the only source of information: there is always the possibility to make in situ measurements. The satellite-based remote sensing is, however, superior in the sense of speed and coverage if only the scattered signal can be reliably interpreted. The optical properties of many industrial products play a key role in their quality. Especially for products such as paint and paper, the ability to obscure the background and to reflect light is of utmost importance. High-grade papers are evaluated based on their brightness, opacity, color, and gloss. In product development, there is a need for computer-based simulation methods that could predict the optical properties and, therefore, could be used in optimizing the quality while reducing the material costs. With paper, for instance, pilot experiments with an actual paper machine can be very time- and resource-consuming. The light-scattering methods presented in this thesis solve rigorously the interaction of light and material with wavelength-scale structures. These methods are computationally demanding, thus the speed and accuracy of the methods play a key role. Different implementations of the discrete-dipole approximation are compared in the thesis and the results provide practical guidelines in choosing a suitable code. In addition, a novel method is presented for the numerical computations of orientation-averaged light-scattering properties of a particle, and the method is compared against existing techniques. Simulation of light scattering for various targets and the possible problems arising from the finite size of the model target are discussed in the thesis. Scattering by single particles and small clusters is considered, as well as scattering in particulate media, and scattering in continuous media with porosity or surface roughness. Various techniques for modeling the scattering media are presented and the results are applied to optimizing the structure of paper. However, the same methods can be applied in light-scattering studies of Solar-system regoliths or cometary dust, or in any remote-sensing problem involving light scattering in random media with wavelength-scale structures.

Combination antiretroviral therapy -associated lipodystrophy : insights into pathogenesis and treatment

Introduction: Combination antiretroviral therapy (cART) has decreased morbidity and mortality of individuals infected with human immunodeficiency virus type 1 (HIV-1). Its use, however, is associated with adverse effects which increase the patients risk of conditions such as diabetes and coronary heart disease. Perhaps the most stigmatizing side effect is lipodystrophy, i.e., the loss of subcutaneous adipose tissue (SAT) in the face, limbs and trunk while fat accumulates intra-abdominally and dorsocervically. The pathogenesis of cART-associated lipodystrophy is obscure. Nucleoside reverse transcriptase inhibitors (NRTI) have been implicated to cause lipoatrophy via mitochondrial toxicity. There is no known effective treatment for cART-associated lipodystrophy during unchanged antiretroviral regimen in humans, but in vitro data have shown uridine to abrogate NRTI-induced toxicity in adipocytes. Aims: To investigate whether i) cART or lipodystrophy associated with its use affect arterial stiffness; ii) lipoatrophic SAT is inflamed compared to non-lipoatrophic SAT; iii) abdominal SAT from patients with compared to those without cART-associated lipoatrophy differs with respect to mitochondrial DNA (mtDNA) content, adipose tissue inflammation and gene expression, and if NRTIs stavudine and zidovudine are associated with different degree of changes; iv) lipoatrophic abdominal SAT differs from preserved dorsocervical SAT with respect to mtDNA content, adipose tissue inflammation and gene expression in patients with cART-associated lipodystrophy and v) whether uridine can revert lipoatrophy and the associated metabolic disturbances in patients on stavudine or zidovudine based cART. Subjects and methods: 64 cART-treated patients with (n=45) and without lipodystrophy/-atrophy (n=19) were compared cross-sectionally. A marker of arterial stiffness, heart rate corrected augmentation index (AgIHR), was measured by pulse wave analysis. Body composition was measured by magnetic resonance imaging and dual-energy X-ray absorptiometry, and liver fat content by proton magnetic resonance spectroscopy. Gene expression and mtDNA content in SAT were assessed by real-time polymerase chain reaction and microarray. Adipose tissue composition and inflammation were assessed by histology and immunohistochemistry. Dorsocervical and abdominal SAT were studied. The efficacy and safety of uridine for the treatment of cART-associated lipoatrophy were evaluated in a randomized, double-blind, placebo-controlled 3-month trial in 20 lipoatrophic cART-treated patients. Results: Duration of antiretroviral treatment and cumulative exposure to NRTIs and protease inhibitors, but not the presence of cART-associated lipodystrophy, predicted AgIHR independent of age and blood pressure. Gene expression of inflammatory markers was increased in SAT of lipodystrophic as compared to non-lipodystrophic patients. Expression of genes involved in adipogenesis, triglyceride synthesis and glucose disposal was lower and of those involved in mitochondrial biogenesis, apoptosis and oxidative stress higher in SAT of patients with than without cART-associated lipoatrophy. Most changes were more pronounced in stavudine-treated than in zidovudine-treated individuals. Lipoatrophic SAT had lower mtDNA than SAT of non-lipoatrophic patients. Expression of inflammatory genes was lower in dorsocervical than in abdominal SAT. Neither depot had characteristics of brown adipose tissue. Despite being spared from lipoatrophy, dorsocervical SAT of lipodystrophic patients had lower mtDNA than the phenotypically similar corresponding depot of non-lipodystrophic patients. The greatest difference in gene expression between dorsocervical and abdominal SAT, irrespective of lipodystrophy status, was in expression of homeobox genes that regulate transcription and regionalization of organs during embryonal development. Uridine increased limb fat and its proportion of total fat, but had no effect on liver fat content and markers of insulin resistance. Conclusions: Long-term cART is associated with increased arterial stiffness and, thus, with higher cardiovascular risk. Lipoatrophic abdominal SAT is characterized by inflammation, apoptosis and mtDNA depletion. As mtDNA is depleted even in non-lipoatrophic dorsocervical SAT, lipoatrophy is unlikely to be caused directly by mtDNA depletion. Preserved dorsocervical SAT of patients with cART-associated lipodystrophy is less inflamed than their lipoatrophic abdominal SAT, and does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal SAT is in expression of transcriptional regulators, homeobox genes, which might explain the differential susceptibility of these adipose tissue depots to cART-induced toxicity. Uridine is able to increase peripheral SAT in lipoatrophic patients during unchanged cART.

Emergenssi tieteessä ja teologiassa : Huomioita Philip Claytonin emergenssiteoriasta

Tässä työssä tarkastellaan emergenssiä luonnontieteellisenä, metafyysisenä ja teologisena käsitteenä, ja erityisesti Philip Claytonin emergenssiteoriaa. Tutkimuskohteena on Philip Claytonin kirja Mind and Emergence From Quantum to Consciousness ja tutkimusmetodina käsitteellinen analyysi. Kun emergenssiä tarkastellaan metafyysisenä teoriana, se on mahdollista nähdä fysikalismille ja dualismille vaihtoehtoisena filosofisena katsantokantana todellisuuteen. Fysikalismi on havaittavaa todellisuutta koskeva näkemys, jonka mukaan kaikki ilmiöt ovat lopulta palautettavissa fysiikkaan ja selitettävissä fysiikan käsittein. Dualismi taas on näkemys, että erityisesti ihmisen mieli ja tietoisuus ovat jotain fysikaaliseen maailmaan nähden täysin erilaista ja siitä riippumatonta. Emergenssiteoriassa maailman nähdään kehittyvänä kokonaisuutena, jossa kompleksisuuden kasvun myötä syntyy jatkuvasti uusia ominaisuuksia. Nämä ominaisuudet eivät ole palautettavissa niihin rakenteisiin, joiden pohjalta ne ovat syntyneet. Niiden syntymistä ei ole mahdollista luonnontieteellisin tai muinkaan menetelmin ennakoida. Emergenssin heikossa muodossa tämä ennakoimattomuus on vain episteeminen, tiedon mahdollisuuksiin liittyvä rajoitus, ja kausaalisia vaikutuksia esiintyy ainoastaan fysikaalisten objektien tasolla. Metafyysinen teoria edellyttää kuitenkin vahvaa emergenssiä, jossa syntyvillä ominaisuuksilla on fysikaalisesta perustastaan riippumatonta kausaalista vaikutusta. Tätä kutsutaan alaspäin -kausaalisuudeksi. Käsitys todellisuudesta on monistinen ja holistinen. Kaikki olemassa oleva on kehittynyt samasta aineksesta, mutta ei ole palautettavissa siihen. Maailmassa on ontologisesti toisistaan poikkeavia todellisuuden tasoja. Todellisuus on enemmän kuin osiensa summa. Emergenssille on tarjottu myös teologisia sovelluksia. Kun fysikalismissa uskonnolliselle uskolle ei jää tilaa ja dualismi on luonnontieteen näkökulmasta ongelmallinen, emergenssistä on etsitty filosofista viitekehystä, jossa luonnontiede ja uskonto olisivat sovitettavissa yhteen. Ensimmäisessä luvussa käsitellään fysikalismia ja dualismia ja erityisesti filosofista ja luonnontieteellistä kritiikkiä, jota niitä vastaan voidaan esittää. Toisessa luvussa tarkastellaan erilaisia mahdollisuuksia määritellä emergenssin käsite ja esitellään erityisesti Philip Claytonin käsityksiä heikosta ja vahvasta emergenssistä, emergenssistä luonnontieteissä sekä ihmismielestä fysikaaliseen maailmaan nähden emergenttinä ilmiönä. Emergenssi mainitaan monien sellaisten ilmiöiden yhteydessä, joita on pyritty tutkimaan kaaosteorian ja kompleksisuuden tutkimuksen keinoin. Työn kolmannessa luvussa pyritään antamaan kuva emergenssin suhteesta näihin teorioihin ja ylipäätään moderniin fysiikkaan. Philip Clayton on luonut emergenssiteorian pohjalta myös teologisen teorian, jossa käsitys Jumalasta luojana ja Jumalan vaikutus maailmassa pyritään sovittamaan yhteen emergentin todellisuuskäsityksen kanssa. Tätä teologista teoriaa esitellään ja arvioidaan työn neljännessä luvussa.