Lipotoxicity in Obesity and Coronary Artery Disease. Studies by PET, CT and MR

Lipotoxicity is a condition in which fatty acids (FAs) are not efficiently stored in adipose tissue and overflow to non-adipose tissue, causing organ damages. A defect of adipose tissue FA storage capability can be the primary culprit in the insulin resistance condition that characterizes many of the severe metabolic diseases that affect people nowadays. Obesity, in this regard, constitutes the gateway and risk factor of the major killers of modern society, such as cardiovascular disease and cancer. A deep understanding of the pathogenetic mechanisms that underlie obesity and the insulin resistance syndrome is a challenge for modern medicine. In the last twenty years of scientific research, FA metabolism and dysregulations have been the object of numerous studies. Development of more targeted and quantitative methodologies is required on one hand, to investigate and dissect organ metabolism, on the other hand to test the efficacy and mechanisms of action of novel drugs. The combination of functional and anatomical imaging is an answer to this need, since it provides more understanding and more information than we have ever had. The first purpose of this study was to investigate abnormalities of substrate organ metabolism, with special reference to the FA metabolism in obese drug-naïve subjects at an early stage of disease. Secondly, trimetazidine (TMZ), a metabolic drug supposed to inhibit FA oxidation (FAO), has been for the first time evaluated in obese subjects to test a whole body and organ metabolism improvement based on the hypothesis that FAO is increased at an early stage of the disease. A third objective was to investigate the relationship between ectopic fat accumulation surrounding heart and coronaries, and impaired myocardial perfusion in patients with risk of coronary artery disease (CAD). In the current study a new methodology has been developed with PET imaging with 11C-palmitate and compartmental modelling for the non-invasive in vivo study of liver FA metabolism, and a similar approach has been used to study FA metabolism in the skeletal muscle, the adipose tissue and the heart. The results of the different substudies point in the same direction. Obesity, at the an early stage, is associated with an impairment in the esterification of FAs in adipose tissue and skeletal muscle, which is accompanied by the upregulation in skeletal muscle, liver and heart FAO. The inability to store fat may initiate a cascade of events leading to FA oversupply to lean tissue, overload of the oxidative pathway, and accumulation of toxic lipid species and triglycerides, and it was paralleled by a proportional growth in insulin resistance. In subjects with CAD, the accumulation of ectopic fat inside the pericardium is associated with impaired myocardial perfusion, presumably via a paracrine/vasocrine effect. At the beginning of the disease, TMZ is not detrimental to health; on the contrary at the single organ level (heart, skeletal muscle and liver) it seems beneficial, while no relevant effects were found on adipose tissue function. Taken altogether these findings suggest that adipose tissue storage capability should be preserved, if it is not possible to prevent excessive fat intake in the first place.

Välimiehen vahingonkorvausvastuu

Tutkielman tavoitteena on selvittää välimiehen vahingonkorvausoikeudellista asemaa suhteessa välimiesmenettelyn asianosaisiin ja välimiehen korvausvastuuta eri tilanteissa välimiesmenettelystä annetun lain mukaisessa sopimusperusteisessa välimiesmenettelyssä. Tutkielma on menetelmältään lainopillinen ja tutkielman aineisto koostuu pääosin oikeuskirjallisuudesta. Välimiehen ja asianosaisten välinen oikeussuhde voidaan katsoa rinnastuvan sopimussuhteeseen, mikä mahdollistaa sopimusperusteisen vahingonkorvausvastuun normien soveltamisen. Välimiehen korvausvastuu vaikuttaa mahdolliselta – vaikkakin käytännössä harvinaiselta – menettelyn viivästymisen, välimiehen aiheettoman tehtävästä luopumisen sekä välitystuomion mitättömyyden ja kumoamisen perusteella. Vastuu vaikuttaa syntyvän helpommin sellaisissa välimiehen velvoitteen rikkomistilanteissa, joissa välimiehen menettely ei edellytä oikeudellista harkintaa. Korvausvastuun arviointiin vaikuttavat useiden perusteiden osalta tilannekohtaiset tekijät ja välimiehen velvoitteen tulkinnanvaraisuus voi sulkea pois korvausvastuun. Välimiehen vastuun syntyminen salassapitovelvollisuuden rikkomisen perusteella on monilta osin epäselvä johtuen välimiehen salassapitovelvollisuuden heikosta normipohjasta. Vastuu välitystuomion aineellisoikeudellisen virheellisyyden perusteella vaikuttaa hyvin epätodennäköiseltä.

Pankin notariaattipalvelut – asiantuntijan vastuu sivullista kohtaan

Pro gradu -tutkimuksen keskeisin tavoite on selvittää perusteita pankin notariaattipalveluiden tarjoajan vastuun laajenemiselle yli välittömän toimeksiantosopimussuhteen. Tutkimus on rajattu vain Suomen oikeuteen ja tutkimusasetelmasta seuraa, että vastuun henkilöllisen ulottuvuuden laajentumisen tilanteista tutkimuksessa perehdytään nimenomaisesti sivullisintressitilanteisiin. Tutkimus on toteutettu lainopillisesti. Suomen laissa ei säädetä suoraan välittömän sopimussuhteen ylittävästä vastuusta, joten lainsäädännön jäädessä vähemmälle korostuvat tutkimuksessa sopimusoikeuden yleiset periaatteet sekä korkeimman oikeuden tulkintakäytäntö ja oikeustieteellinen tutkimus. Tämä johtaa etsimään ja jäsentämään tutkimusongelman kannalta merkityksellisiä oikeusperiaatteita ja reaalisia argumentteja tarkkojen tulkintasuositusten tarjoamisen sijaan. Tutkimus osoittaa, että välittömän sopimussuhteen ylittävää vastuuta tulee arvioida sopimusvastuun normien mukaisesti deliktivastuun sijaan, ja sitä voidaan pitää eräänä sopimusvastuun erityistapauksena. Tutkimuksen pohjalta voidaan todeta, että pankin notariaattipalveluiden tarjoajan vastuu voi ulottua yli toimeksiantosopimussuhteen, jos vastuun syntymistä voidaan puoltaa riittävillä reaalisilla argumenteilla. Tällaisia perusteita ovat muun muassa pankin notariaattipalvelun tarjoajan ja sivullisen välinen erityissuhde ja pankin notariaattipalvelun tarjoajan mahdollisuus ennakoida vahinkoriski. Lisäksi kaksiasianosaissuhteen rajoituksesta poikkeamista voidaan perustella vaihdannan reaalisen rakenteen huomioonottamisella sekä sivulliselle syntyneellä perustellun luottamuksen suojaamisella.

Sustainable Gold Mining- Life Cycle Assessment of Cyanidation and Thiosulphate Leaching

With the increasing concern of the sustainable approach of gold mining, thiosulphate has been researched as an alternative lixiviant to cyanide since cyanide is toxic to the environment. In order to investigate the possibility of thiosulphate leaching application in the coming future, life cycle assessment, is conducted to compare the environmental footprint of cyanidation and thiosulphate leaching. The result showed the most significant environmental impact of cyanidation is toxicity to human, while the ammonia of thiosulphate leaching is also a major concern of acidification. In addition, an ecosystem evaluation is also performed to indicate the potential damages caused by an example of cyanide spill at Kittilä mine, resulting in significant environmental risk cost that has to be taken into account for decision making. From the opinion collected from an online LinkedIn discussion forum, the anxiety of sustainability alone would not be enough to contribute a significant change of conventional cyanidation, until the tighten policy of cyanide use. International Cyanide Code, therefore, is crucial for safe gold production. Nevertheless, it is still thoughtful to consider the values of healthy ecosystem and the gold for long-term benefit.

Effects of the partial removal of wood hemicelluloses on the properties of kraft pulp

The objective of this work was to study the effects of partial removal of wood hemicelluloses on the properties of kraft pulp.The work was conducted by extracting hemicelluloses (1) by a softwood chip pretreatment process prior to kraft pulping, (2) by alkaline extraction from bleached birch kraft pulp, and (3) by enzymatic treatment, xylanase treatment in particular, of bleached birch kraft pulp. The qualitative and quantitative changes in fibers and paper properties were evaluated. In addition, the applicability of the extraction concepts and hemicellulose-extracted birch kraft pulp as a raw material in papermaking was evaluated in a pilot-scale papermaking environment. The results showed that each examined hemicellulose extraction method has its characteristic effects on fiber properties, seen as differences in both the physical and chemical nature of the fibers. A prehydrolysis process prior to the kraft pulping process offered reductions in cooking time, bleaching chemical consumption and produced fibers with low hemicellulose content that are more susceptible to mechanically induced damages and dislocations. Softwood chip pretreatment for hemicellulose recovery prior to cooking, whether acidic or alkaline, had an impact on the physical properties of the non-refined and refined pulp. In addition, all the pretreated pulps exhibited slower beating response than the unhydrolyzed reference pulp. Both alkaline extraction and enzymatic (xylanase) treatment of bleached birch kraft pulp fibers indicated very selective hemicellulose removal, particularly xylan removal. Furthermore, these two hemicellulose-extracted birch kraft pulps were utilized in a pilot-scale papermaking environment in order to evaluate the upscalability of the extraction concepts. Investigations made using pilot paper machine trials revealed that some amount of alkalineextracted birch kraft pulp, with a 24.9% reduction in the total amount of xylan, could be used in the papermaking stock as a mixture with non-extracted pulp when producing 75 g/m2 paper. For xylanase-treated fibers there were no reductions in the mechanical properties of the 180 g/m2 paper produced compared to paper made from the control pulp, although there was a 14.2% reduction in the total amount of xylan in the xylanase-treated pulp compared to the control birch kraft pulp. This work emphasized the importance of the hemicellulose extraction method in providing new solutions to create functional fibers and in providing a valuable hemicellulose co-product stream. The hemicellulose removal concept therefore plays an important role in the integrated forest biorefinery scenario, where the target is to the co-production of hemicellulose-extracted pulp and hemicellulose-based chemicals or fuels.

Graphene from Graphite by Chemical and Physical Techniques.

Graphene is a material with extraordinary properties. Its mechanical and electrical properties are unparalleled but the difficulties in its production are hindering its breakthrough in on applications. Graphene is a two-dimensional material made entirely of carbon atoms and it is only a single atom thick. In this work, properties of graphene and graphene based materials are described, together with their common preparation techniques and related challenges. This Thesis concentrates on the topdown techniques, in which natural graphite is used as a precursor for the graphene production. Graphite consists of graphene sheets, which are stacked together tightly. In the top-down techniques various physical or chemical routes are used to overcome the forces keeping the graphene sheets together, and many of them are described in the Thesis. The most common chemical method is the oxidisation of graphite with strong oxidants, which creates a water-soluble graphene oxide. The properties of graphene oxide differ significantly from pristine graphene and, therefore, graphene oxide is often reduced to form materials collectively known as reduced graphene oxide. In the experimental part, the main focus is on the chemical and electrochemical reduction of graphene oxide. A novel chemical route using vanadium is introduced and compared to other common chemical graphene oxide reduction methods. A strong emphasis is placed on electrochemical reduction of graphene oxide in various solvents. Raman and infrared spectroscopy are both used in in situ spectroelectrochemistry to closely monitor the spectral changes during the reduction process. These in situ techniques allow the precise control over the reduction process and even small changes in the material can be detected. Graphene and few layer graphene were also prepared using a physical force to separate these materials from graphite. Special adsorbate molecules in aqueous solutions, together with sonic treatment, produce stable dispersions of graphene and few layer graphene sheets in water. This mechanical exfoliation method damages the graphene sheets considerable less than the chemical methods, although it suffers from a lower yield.

Novel Cellular Luminescence Probes for Immunological and Toxicological Assessments

Escherichia coli K-12 (pEGFPluxABCDEAmp) (E. coli-lux), constitutively emitting bioluminescence (BL), was constructed and its BL emitting properties tested in different growth and killing conditions. The BL emission directly correlated with the number of viable E. coli-lux cells, and when subjected to the antimicrobial agent, the diminishment of the BL signal was linked directly to the number of killed bacterial cells. The method provided a very convenient application, especially when compared to conventional plate counting assays. This novel real-time based method was utilized in both immunological and toxicological assessments. The parameters such as the activation phase, the lytic phase and the capacity of the killing of the serum complement system were specified not only in humans but also in other species. E. coli-lux was also successfully used to study the antimicrobial activities of insect haemolymph. The mechanisms of neutrophil activity, like that of a myeloperoxidase (MPO)-H2O2-halide system, were studied using the E. coli-lux approach. The fundamental role of MPO was challenged, since during the actual killing in described circumstances in phagolysosome the MPO system was inactivated and chlorination halted. The toxicological test system, assessing indoor air total toxicity, particularly suitable for suspected mold damages, was designed based on the E. coli-lux method. Susceptibility to the vast number of various toxins, both pure chemicals and dust samples from the buildings and extracts from molds, were investigated. The E. coli-lux application was found to possess high sensitivity and specificity attributes. Alongside the analysis system, the sampling kit for indoor dust was engineered based on the swipe stick and the container. The combination of practical specimen collector and convenient analysis system provided accurate toxic data from the dust sample within hours. Neutrophils are good indicators of the pathophysiological state of the individual, and they can be utilized as a toxicological probe due to their ability to emit chemiluminescence (CL). Neutrophils can either be used as probe cells, directly exposed to the agent studied, or they can act as indicators of the whole biological system exposed to the agent. Human neutrophils were exposed to the same toxins as tested with the E. coli-lux system and measured as luminol amplified CL emission. The influence of the toxins on the individuals was investigated by exposing rats with moniliniformin, the mycotoxin commonly present in Finnish grains. The activity of the rat neutrophils was found to decrease significantly during the 28 days of exposure.

Sellumassan varastosäiliön rakenneanalyysi

Tämä työ käsittelee valkaistun ja valkaisemattoman sellumassan varastosäiliön tärinää ja värähtelyä. Värähtelyn seurauksena säiliön seinämän jäykisterenkaan hitsausliitokseen on syntynyt särö. Työn tavoitteena on selvittää, mikä johtaa särön syntyyn ja miten kestäväm-piä varastosäiliöitä voidaan rakentaa materiaali-, valmistus- tai rakennemuutoksien avulla. Työ alkoi tutkimalla rakennemateriaalina olevan duplex-teräksen mikrorakenteen ominai-suuksia, sekä sen hitsattavuutta ja seostamista kirjallisuustutkimuksena. Kirjallisuustutki-musta jatkettiin selvittämällä mahdollisia vaurion syntymekanismeja seinämän särölle. Työssä analysoitiin myös tehtaalla mitattuja värähtelyarvoja. Lopuksi laskettiin FE-analyysillä tyhjän varastosäiliön ominaismuodot ja -taajuudet moodianalyysillä, sekä selvi-tettiin harmonisella analyysillä pinnankorkeuden vaihtelun vaikutus siirtymävasteeseen ja kriittisiin värähtelytaajuuksiin. Varastosäiliöön kohdistuvaa värähtelyä ei ole mahdollista poistaa kokonaan, mutta väräh-telyn aiheuttamia seurauksia kyetään rajaamaan useilla keinoilla. Toimenpiteinä voivat olla ainakin seinämän materiaalin paksuuden lisääminen, jäykisteripojen lisääminen ja kriittisten sellun pinnankorkeuksien välttäminen. Kriittiseksi pinnankorkeudeksi havaittiin 40–45 %:n täyttöaste ja turvalliseksi korkeudeksi 35–38 %:n täyttöaste. Varastosäiliölle kriittisen ominaistaajuuden katsotaan syntyvän taajuuksilla 3,3–3,8 Hz ja 5,8–6,4 Hz. Sellumassa putoaa varastosäiliöön noin 2 Hz taajuudella.

Multibody models for examination of touchdown bearing systems

Increased rotational speed brings many advantages to an electric motor. One of the benefits is that when the desired power is generated at increased rotational speed, the torque demanded from the rotor decreases linearly, and as a consequence, a motor of smaller size can be used. Using a rotor with high rotational speed in a system with mechanical bearings can, however, create undesirable vibrations, and therefore active magnetic bearings (AMBs) are often considered a good option for the main bearings, as the rotor then has no mechanical contact with other parts of the system but levitates on the magnetic forces. On the other hand, such systems can experience overloading or a sudden shutdown of the electrical system, whereupon the magnetic field becomes extinct, and as a result of rotor delevitation, mechanical contact occurs. To manage such nonstandard operations, AMB-systems require mechanical touchdown bearings with an oversized bore diameter. The need for touchdown bearings seems to be one of the barriers preventing greater adoption of AMB technology, because in the event of an uncontrolled touchdown, failure may occur, for example, in the bearing’s cage or balls, or in the rotor. This dissertation consists of two parts: First, touchdown bearing misalignment in the contact event is studied. It is found that misalignment increases the likelihood of a potentially damaging whirling motion of the rotor. A model for analysis of the stresses occurring in the rotor is proposed. In the studies of misalignment and stresses, a flexible rotor using a finite element approach is applied. Simplified models of cageless and caged bearings are used for the description of touchdown bearings. The results indicate that an increase in misalignment can have a direct influence on the bending and shear stresses occurring in the rotor during the contact event. Thus, it was concluded that analysis of stresses arising in the contact event is essential to guarantee appropriate system dimensioning for possible contact events with misaligned touchdown bearings. One of the conclusions drawn from the first part of the study is that knowledge of the forces affecting the balls and cage of the touchdown bearings can enable a more reliable estimation of the service life of the bearing. Therefore, the second part of the dissertation investigates the forces occurring in the cage and balls of touchdown bearings and introduces two detailed models of touchdown bearings in which all bearing parts are modelled as independent bodies. Two multibody-based two-dimensional models of touchdown bearings are introduced for dynamic analysis of the contact event. All parts of the bearings are modelled with geometrical surfaces, and the bodies interact with each other through elastic contact forces. To assist in identification of the forces affecting the balls and cage in the contact event, the first model describes a touchdown bearing without a cage, and the second model describes a touchdown bearing with a cage. The introduced models are compared with the simplified models used in the first part of the dissertation through parametric study. Damages to the rotor, cage and balls are some of the main reasons for failures of AMB-systems. The stresses in the rotor in the contact event are defined in this work. Furthermore, the forces affecting key bodies of the bearings, cage and balls can be studied using the models of touchdown bearings introduced in this dissertation. Knowledge obtained from the introduced models is valuable since it can enable an optimum structure for a rotor and touchdown bearings to be designed.

Impact of Product-harm Crisis on Brand Equity: the Moderating Role of Corporate Social Performance

There is an increasing amount of product-harm crisis in the past few years; and the impact of a product-harm crisis becomes more and more influential due to the high increasing speed of globalization. And it is believed that the negative damages to a firm leading to a loss of the intangible assets is bigger than other costs such as the cost of the product recall. Brand equity is a very important and valuable intangible asset for a firm; and it is particularly vulnerable during the crisis. And CSP (CSP) is a hot concept associated with product-harm crisis and brand equity. The aim of this study is to understand how product-harm crisis influences by simultaneously involving CSP as a moderator in a consumer-based level. An experimental study was conducted through an online questionnaire among 198 students in Finland. The questionnaire mainly assessed the consumers’ attitudes towards CSP and brand before/after a fictional product-harm crisis. The results shows that the brand equity was negatively related to the product-harm crisis. And the extent level of crisis’s severity was positively related to the loss of the brand equity; whereas, acknowledged blame was more useful to compensate the loss of brand equity in the low-severity crisis. CSP acted as a moderator role which could compensate the loss of brand equity caused by the product-harm crisis. Managerial implications are also offered for crisis managers, brand managers, and CSR managers.

Analysis of Automotive Cybersecurity - Attack surfaces and users’ privacy concerns

Modern automobiles are no longer just mechanical tools. The electronics and computing services they are shipping with are making them not less than a computer. They are massive kinetic devices with sophisticated computing power. Most of the modern vehicles are made with the added connectivity in mind which may be vulnerable to outside attack. Researchers have shown that it is possible to infiltrate into a vehicle’s internal system remotely and control the physical entities such as steering and brakes. It is quite possible to experience such attacks on a moving vehicle and unable to use the controls. These massive connected computers can be life threatening as they are related to everyday lifestyle. First part of this research studied the attack surfaces in the automotive cybersecurity domain. It also illustrated the attack methods and capabilities of the damages. Online survey has been deployed as data collection tool to learn about the consumers’ usage of such vulnerable automotive services. The second part of the research portrayed the consumers’ privacy in automotive world. It has been found that almost hundred percent of modern vehicles has the capabilities to send vehicle diagnostic data as well as user generated data to their manufacturers, and almost thirty five percent automotive companies are collecting them already. Internet privacy has been studies before in many related domain but no privacy scale were matched for automotive consumers. It created the research gap and motivation for this thesis. A study has been performed to use well established consumers privacy scale – IUIPC to match with the automotive consumers’ privacy situation. Hypotheses were developed based on the IUIPC model for internet consumers’ privacy and they were studied by the finding from the data collection methods. Based on the key findings of the research, all the hypotheses were accepted and hence it is found that automotive consumers’ privacy did follow the IUIPC model under certain conditions. It is also found that a majority of automotive consumers use the services and devices that are vulnerable and prone to cyber-attacks. It is also established that there is a market for automotive cybersecurity services and consumers are willing to pay certain fees to avail that.