Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Tertiary Treatment and Re-use of Kraft Pulp Mill Effluent

The efficient use of materials and natural recourses, for ecological and economic reasons, has become more and more important in all industries. In the forest industries this means higher levels of closure in the material circulations of the mills. One possibility to reduce wastewater discharge is to re-use part of the 2nd clarifier effluent as process water. The main target of this thesis was to evaluate the technical suitability of several mechanical and chemical tertiary treatment methods for water re-use. Some of the tested methods seemed to have high potential for the removal of some specific constituents from the wastewater. Tertiary treatment is needed because higher levels of closure may cause problems with increasing amounts of non-process elements in different points of kraft pulp process. The aspect of sustainable development was taken into account by evaluating positive and negative environmental effects of the treatment processes. Environmental benefits can be gained by using some of the tertiary treatment methods tested. These methods should still be researched more for system optimization.

Treatment of Fe-containing Acid Mine Waters in Fixed Bed Adsorption Column with Calcite Side-Stone

The acid mining drainage is considered the most significant environmental pollution problem around the world for the extensive formation acidic leachates containing heavy metals. Adsorption is widely used methods in water treatment due to it easy operation and the availability of a wide variety of commercial adsorbent (low cost). The primary goal of this thesis was to investigate the efficiency of neutralizing agents, CaCO3 and CaSiO3, and metal adsorption materials with unmodified limestone from Company Nordkalk Oy. In addition to this, the side materials of limestone mining were tested for iron adsorption from acidic model solution. This study was executed at Lappeenranta University of Technology, Finland. The work utilised fixed-bed adsorption column as the main equipment and large fluidized column. Atomic absorption spectroscopy (AAS) and x-ray diffraction (XRD) was used to determine ferric removal and the composition of material respectively. The results suggest a high potential for the studied materials to be used a low cost adsorbents in acid mine drainage treatment. From the two studied adsorbents, the FS material was more suitable than the Gotland material. Based on the findings, it is recommended that further studies might include detailed analysis of Gotland materials.

Monolithic zirconium dioxide as a full contour restorative material: With special emphasis on the optical and mechanical properties

Full contour monolithic zirconia restorations have shown an increased popularity in the dental field over the recent years, owing to its mechanical and acceptable optical properties. However, many features of the restoration are yet to be researched and supported by clinical studies to confirm its place among the other indirect restorative materials This series of in vitro studies aimed at evaluating and comparing the optical and mechanical properties, light cure irradiance, and cement polymerization of multiple monolithic zirconia material at variable thicknesses, environments, treatments, and stabilization. Five different monolithic zirconia materials, four of which were partially stabilized and one fully stabilized were investigated. The optical properties in terms of surface gloss, translucency parameter, and contrast ratio were determined via a reflection spectrophotometer at variable thicknesses, coloring, sintering method, and after immersion in an acidic environment. Light cure irradiance and radiant exposure were quantified through the specimens at variable thicknesses and the degree of conversion of two dual-cure cements was determined via Fourier Transform Infrared spectroscopy. Bi-axial flexural strength was evaluated to compare between the partially and fully stabilized zirconia prepared using different coloring and sintering methods. Surface characterization was performed using a scanning electron microscope and a spinning disk confocal microscope. The surface gloss and translucency of the zirconia investigated were brand and thickness dependent with the translucency values decreasing as the thickness increased. Staining decreased the translucency of the zirconia and enhanced surface gloss as well as the flexural strength of the fully stabilized zirconia but had no effect on partially stabilized zirconia. Immersion in a corrosive acid increased surface gloss and decreased the translucency of some zirconia brands. Zirconia thickness was inversely related to the amount of light irradiance, radiant exposure, and degree of monomer conversion. Type of sintering furnace had no effect on the optical and mechanical properties of zirconia. Monolithic zirconia maybe classified as a semi-translucent material that is well influenced by the thickness, limiting its use in the esthetic zones. Conventional acid-base reaction, autopolymerizing and dual-cure cements are recommended for its cementation. Its desirable mechanical properties give it a high potential as a restoration for posterior teeth. However, close monitoring with controlled clinical studies must be determined before any definite clinical recommendations can be drawn.

Functionalisation of spruce O-acetyl-galactoglucomannans for barrier and composite applications

The increasing use of energy, food, and materials by the growing population in the world is leading to the situation where alternative solutions from renewable carbon resources are sought after. The growing use of plastics depends on the raw-oil production while oil refining are politically governed and required for the polymer manufacturing is not sustainable in terms of carbon footprint. The amount of packaging is also increasing. Packaging is not only utilising cardboard and paper, but also plastics. The synthetic petroleum-derived plastics and inner-coatings in food packaging can be substituted with polymeric material from the renewable resources. The trees in Finnish forests constitute a huge resource, which ought to be utilised more effectively than it is today. One underutilised component of the forests is the wood-derived hemicelluloses, although Spruce Oacetyl-galactoglucomannans (GGMs) have previously shown high potential for material applications and can be recovered in large scale. Hemicelluloses are hydrophilic in their native state, which restrains the use of them for food packaging as non-dry item. To cope with this challenge, we intended to make GGMs more hydrophobic or amphiphilic by chemical grafting and consequently with the focus of using them for barrier applications. Methods of esterification with anhydrides and cationic etherification with a trimethyl ammonium moiety were established. A method of controlled synthesis to obtain the desired properties by the means of altering temperature, reaction time, the quantity of the reagent, and even the solvent for purification of the products was developed. Numerous analytical tools, such as NMR, FTIR, SEC-MALLS/RI, MALDI-TOF-MS, RP-HPLC and polyelectrolyte titration were used to evaluate the products from different perspectives and to acquire parallel proofs of their chemical structure. Modified GGMs with different degree of substitution and the correlating level of hydrophobicity was applied as coatings on cartonboard and on nanofibrillated cellulose-GGM films to exhibit barrier functionality. The water dispersibility in processing was maintained with GGM esters with low DS. The use of chemically functionalised GGM was evaluated for the use as barriers against water, oxygen and grease for the food packaging purposes. The results show undoubtedly that GGM derivatives exhibit high potential to function as a barrier material in food packaging.

Lohkoketjuteknologian soveltaminen finanssisektorille

Tämän kandidaatintutkielman tarkoituksena on tutkia, miten lohkoketjuteknologiaa voi soveltaa finanssisektorille. Tutkimus tarjoaa yleiskuvan lohkoketjuteknologista, sekä sen sovelluskohteista finanssisektorilla. Tutkimusmenetelmä on kvalitatiivinen ja se toteutettiin haastattelemalla pankkeja, jotka osallistuvat Distributed Ledger Group (DLG)-konsortioon. Kyseinen konsortio pyrkii 42 pankin ja R3cev nimisen yrityksen välisessä yhteistyössä soveltamaan lohkoketjuteknologiaa pankkisektorille. Haastattelujen perusteella pankit pitävät lohkoketjuteknologian potentiaalia pitkällä aikavälillä suurena. Erityisesti lohkoketjuteknologian odotetaan laskevan kustannuksia, sekä nopeuttavan toimintoja useiden eri tuotteiden kohdalla. Pelkästään pankkisektorilla tutkitaan tällä hetkellä kymmeniä eri sovelluskohteita. Ennen kuin lohkoketjulla voidaan nähdä kaupallista toimintaa, tulee haasteita ylittää sekä teknisellä, että säädännöllisellä puolella. Vielä on liian varhaista arvioida, milloin lohkoketjuteknologiaa tullaan soveltamaan laajemmin finanssisektorilla. Pankkien oma tutkimus aiheesta oli vielä suhteellisen varhaisessa vaiheessa. Lohkoketjuteknologian potentiaali voidaan nähdä tutkimuksen perusteella valtavan suurena. Vielä on kuitenkin vaikea arvioida tullaanko tähän potentiaaliin tulevaisuudessa yltämään. Finanssisektorilla on monia toimijoita, jotka tutkivat lohkoketjuteknologiaa ja se vauhdittaa kehitystä. Lohkoketjuteknologia saattaa tulevaisuudessa mullistaa monia finanssisektorin osa-alueita tai jopa korvata ne kokonaan.

How to reach more potential global b2b customers to Finnish high tech company websites

This thesis examines the optimization of a website in terms of creating website visibility and interesting and attractive online information, with the aim of finding ways how the case company can increase the number of online visitors for the websites, who would even-tually contact the case company, and become customers. The theoretical part concentrates on website visibility, academic knowledge about search engine optimization, integrated marketing communications, website effectiveness and influence tactics (mostly non-coercive) in an online b2b buying context. The empirical part included an experiment of two weeks on the case website. Search engine optimization requires the most relevant key terms and keywords to be selected and carefully implemented to meta descriptions of the most informational pages. The information visible to visitors on these pages was also opti-mized to make it interesting and purposeful for the targeted audience. The most suitable influence tactics were implemented to certain pages to attract the website visitors to con-tact the case company. The results suggest that relevant key terms in meta descriptions do improve, or maintain the same high, ranking a page has on search engine result pages, but this is not directly connected to the amount of visitors to the website. The number of visi-tors does not either affect the amount of customer contacts the company received during the experiment period.

High speed release -mittausmenetelmän käyttäminen tarralaminaattiprosessin ohjaukses

Työn tavoitteena oli tutkia HSR(High Speed Release)-mittausmenetelmän käyttämistä tarralaminaattiprosessin ohjauksessa UPM Raflatacissa. Nykyisin käytössä olevaan LSR(Low Speed Release)-menetelmään verrattuna HSR-menetelmä kuvaa paremmin tarralaminaatin jatkojalostuksessa sekä etiketöinnissä tapahtuvaa irrotustyötä. Lisäksi työssä tutkittiin irrotusnopeuden vaikutusta HSR-arvoon. Työn kirjallisuusosassa perehdyttiin tarralaminaatin rakenteeseensekä valmistusprosessiin. Koska silikonin valinnalla on merkittävä vaikutus tarralaminaatin releasearvoon, kirjallisessa osassa syvennytään tarkastelemaan tarralaminaatin valmistuksessa käytettyjä silikoneja sekänäiden rakennetta. Kirjallisuusosassa on myös käsitelty muita releasetasoon vaikuttavia tekijöitä. Työn kokeellisessa osassa oli tarkoituksena tutkia HSR-mittausmenetelmän käytettävyyttä tarralaminaatin prosessinohjauksessa. Tätä tutkittiin selvittämällä nykyisin käytössä olevan LSR-menetelmän sekä HSR-menetelmän välistä korreloituvuutta. Mikäli näidenvälillä olisi korreloituvuutta, voitaisiin prosessinohjauksessa ajatella siirtyvän HSR-mittaukseen. Korrelaatiota näiden kahden menetelmän välille ei kuitenkaan löydetty. Työssä tutkittiin myös irrotusnopeuden vaikutusta tuotteen HSR-arvoon. Testeihin valittiin useita eri tuotteita useilta tuotantolaitoksilta. Kaikilla näillä tuotteilla releasearvo kasvoi irrotusnopeutta lisättäessä. Lisäksi työssä määritettiin uudet HSR-spesifikaatiot tietyille tuotteille. Kaikille UPM Raflatacin tuotteille on määritetty LSRspesifikaatiot, HSR-spesifikaatiot on asetettu vain tietyille tuotteille.

Laser Cutting of Austenitic Stainless Steel with a High Quality Laser Beam

The thin disk and fiber lasers are new solid-state laser technologies that offer a combinationof high beam quality and a wavelength that is easily absorbed by metal surfacesand are expected to challenge the CO2 and Nd:YAG lasers in cutting of metals ofthick sections (thickness greater than 2mm). This thesis studied the potential of the disk and fiber lasers for cutting applications and the benefits of their better beam quality. The literature review covered the principles of the disk laser, high power fiber laser, CO2 laser and Nd:YAG laser as well as the principle of laser cutting. The cutting experiments were made with thedisk, fiber and CO2 lasers using nitrogen as an assist gas. The test material was austenitic stainless steel of sheet thickness 1.3mm, 2.3mm, 4.3mm and 6.2mm for the disk and fiber laser cutting experiments and sheet thickness of 1.3mm, 1.85mm, 4.4mm and 6.4mm for the CO2 laser cutting experiments. The experiments focused on the maximum cutting speeds with appropriate cut quality. Kerf width, cutedge perpendicularity and surface roughness were the cut characteristics used to analyze the cut quality. Attempts were made to draw conclusions on the influence of high beam quality on the cutting speed and cut quality. The cutting speeds were enormous for the disk and fiber laser cutting experiments with the 1.3mm and 2.3mm sheet thickness and the cut quality was good. The disk and fiber laser cutting speeds were lower at 4.3mm and 6.2mm sheet thickness but there was still a considerable percentage increase in cutting speeds compared to the CO2 laser cutting speeds at similar sheet thickness. However, the cut quality for 6.2mm thickness was not very good for the disk and fiber laser cutting experiments but could probably be improved by proper selection of cutting parameters.

Strategy Formulation and Implementation Case of High Tech Instruments

The strategy process is a method for strategy formulation and implementation. The strategy process is commonly used especially within bigger companies. It is important to link the strategy formulation and implementation. The objective of this thesis has been to find out improvement areas for the case company’s strategy process. The theoretical framework based on literature emphasizes on strategy process as a method for strategy formulation and implementation. The theoretical framework, several mainly ad hoc interviews and author’s observation were used as tools to analyze the case company’s strategy process. The hierarchy in between the various corporate levels provides the foundation to formulate and implement the strategies. These strategies include the corporate and strategic business area level strategies. The recommendations to improve the case company’s strategy process were formulated at corporate and strategic business area levels. These recommendations were formulated based on research and experience gained throughout the work. The role of strategic projects to implement the strategies more efficiently and organizational control over distribution were found as potential improvement areas. The resource allocation prioritizing towards the most important strategic projects was also an important improvement area.

Supply chain cost saving potential analysis

Target of this study was to examine the current supply chain with focus on external part and identify the cost potential areas which lie there. The goal was to evaluate the cost save potential and give estimate what would be required in order to realise it. Base data related to study was searched and examined with using company’s enterprise resource planning system. In case feasible two types of scenarios were built in order to describe the scale of save potential. First scenario was theoretical and achieving it would require further investments and second scenario was realistic approach where more limitations were taken into account. The results clearly show that there is high save potential in supply chain costs linked to balance between internal and external operations. Realising of it would require at least minor investments as current internal capacity is not on a level to fully absorb the additional volumes which are needed in order to realise the potential. This study can be used as a basis when starting new projects related to investment needs.

Potential of the Osteoclast’s Proton Pump as a Drug Target in Osteoporosis

Decreasing bone mass during aging predisposes to fractures and it is estimated that every second woman and one in five men will suffer osteoporotic fractures during their lifetime. Bone is an adaptive tissue undergoing continuous remodeling in response to physical and metabolic stimuli. Bone mass decreases through a net negative balance in the bone remodeling process of bone, in which the new bone incompletely replaces the resorbed bone mass. Bone resorption is carried out by the osteoclasts; the bone mineral is solubilized by acidification and the organic matrix is subsequently degraded by proteases. Several classes of drugs are available for prevention of osteoporotic fractures. They act by different mechanisms to increase bone mass, and some of them act mainly as antiresorptives by inhibition of osteoclast formation or their function. Optimally, a drug should act selectively on a specific process, since other processes affected usually result in adverse effects. The purpose of this study was to evaluate whether the osteoclastic vacuolar adenosine trisphosphatases (V-ATPase), which drives the solubilization of bone mineral, can be selectively inhibited despite its ubiquitous cellular functions. The V-ATPase is a multimeric protein composed of 13 subunits of which six possesses two or more isoforms. Selectivity for the osteoclastic V-ATPase could be provided if it has some structural uniqueness, such as a unique isoform combination. The a3 isoform of the 116kDa subunit is inevitable for bone resorption; however, it is also present in, and mainly limited to, the lysosomes of other cells. No evidence of a structural uniqueness of the osteoclastic V-ATPase compared to the lysosomal V-ATPase was found, although this can not yet be excluded. Thus, an inhibitor selective for the a3 isoform would target the lysosomal V-ATPase as well. However, the results suggest that selectivity for bone resorption over lysosomal function can be obtained by two other mechanisms, suggesting that isoform a3 is a valid target. The first is differential compensation; bone resorption depends on the high level of a3 expression, and is not compensated for by other isoforms, while the lower level of a3 in lysosomes of other cells may be partly compensated for. The second mechanism is because the bone resorption process itself is fundamentally different from lysosomal acidification because of the chemistry of bone dissolution and the anatomy of the resorbing osteoclast. By this mechanism, full inhibition of bone resorption is obtained with more than tenfold lower inhibitor concentration than those needed to fully inhibit lysosomal acidification. The two mechanisms are additive. Based on the results, we suggest that bone resorption can be selectively inhibited if VATPase inhibitors that are sufficiently selective for the a3 isoform over the other isoforms are developed.

High-Throughput Screening for Novel Prostate Cancer Drug Targets –Getting Personal

Prostate cancers form a heterogeneous group of diseases and there is a need for novel biomarkers, and for more efficient and targeted methods of treatment. In this thesis, the potential of microarray data, RNA interference (RNAi) and compound screens were utilized in order to identify novel biomarkers, drug targets and drugs for future personalized prostate cancer therapeutics. First, a bioinformatic mRNA expression analysis covering 9873 human tissue and cell samples, including 349 prostate cancer and 147 normal prostate samples, was used to distinguish in silico prevalidated putative prostate cancer biomarkers and drug targets. Second, RNAi based high-throughput (HT) functional profiling of 295 prostate and prostate cancer tissue specific genes was performed in cultured prostate cancer cells. Third, a HT compound screen approach using a library of 4910 drugs and drug-like molecules was exploited to identify potential drugs inhibiting prostate cancer cell growth. Nine candidate drug targets, with biomarker potential, and one cancer selective compound were validated in vitro and in vivo. In addition to androgen receptor (AR) signaling, endoplasmic reticulum (ER) function, arachidonic acid (AA) pathway, redox homeostasis and mitosis were identified as vital processes in prostate cancer cells. ERG oncogene positive cancer cells exhibited sensitivity to induction of oxidative and ER stress, whereas advanced and castrate-resistant prostate cancer (CRPC) could be potentially targeted through AR signaling and mitosis. In conclusion, this thesis illustrates the power of systems biological data analysis in the discovery of potential vulnerabilities present in prostate cancer cells, as well as novel options for personalized cancer management.

Kelvin Probe Force Microscopy (KPFM) characterization of lanthanum lutetium oxide high-k dielectric thin films

Lanthanum lutetium oxide (LaLuO3) thin films were investigated considering their perspective application for industrial microelectronics. Scanning probe microscopy (SPM) techniques permitted to visualize the surface topography and study the electric properties. This work compared both the material properties (charge behavior for samples of 6 nm and 25 nm width) and the applied SPM modes. Particularly, Kelvin probe force microscopy (KPFM) was applied to characterize local potential difference with high lateral resolution. Measurements showed the difference in morphology, chargeability and charge dissipation time for both samples. The polarity effect was detected for this material for the first time. Lateral spreading of the charged spots indicate the diffusive mechanism to be predominant in charge dissipation. This allowed to estimate the diffusion coefficient and mobility. Using simple electrostatic model it was found that charge is partly leaking into the interface oxide layer.

Magnesium hydroxide-based peroxide bleaching of high-brightness mechanical pulps

A high final brightness is desired in most paper and board products. This requires bleaching processes that are able to produce high-brightness pulps. Mechanical pulps are widely bleached for high brightness using alkaline hydrogen peroxide with traditional sodium hydroxide and sodium silicate as additives. With high doses however, peroxide bleaching causes high organic loads in the mill effluent and anionic trash carry-over to papermaking. To alleviate the problems that arise from the use of sodium-based additives in peroxide bleaching, interest in the use of alternative magnesium-based chemicals has increased. In this study, a new, technical high-purity magnesium hydroxide-based bleaching additive was evaluated on laboratory-scale, pilot-scale and mill-scale experiments and trials for its ability to produce a high brightness in peroxide bleaching without the known problems of sodium-based chemicals. The key findings of this study include: a high brightening potential of peroxide bleaching using the Mg(OH)2-based additive, significant reductions (40-70%) in all categories of environmental load, and cationic demand lowered by 60-70% in bleached pulp with no loss in strength properties or in sheet bulk. When used in TMP refiner bleaching, the Mg(OH)2-based additive resulted in savings in specific energy consumption and provided a good bleaching response.