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  • Soinne, Lauri (Helsingin yliopisto, 2009)
    Carotid atherosclerotic disease is a major cause of stroke, but it may remain clinically asymptomatic. The factors that turn the asymptomatic plaque into a symptomatic one are not fully understood, neither are the subtle effects that a high-grade carotid stenosis may have on the brain. The purpose of this study was to evaluate brain microcirculation, diffusion, and cognitive performance in patients with a high-grade stenosis in carotid artery, clinically either symptomatic or asymptomatic, undergoing carotid endarterectomy (CEA). We wanted to find out whether the stenoses are associated with diffusion or perfusion abnormalities of the brain or variation in the cognitive functioning of the patients, and to what extent the potential findings are affected by CEA, and compare the clinically symptomatic and asymptomatic subjects as well as strictly healthy controls. Coagulation and fibrinolytic parameters were compared with the rate microembolic signals (MES) in transcranial Doppler (TCD) and the macroscopic appearance of stenosing plaques in surgery. Patients (n=92) underwent CEA within the study. Blood samples pertaining to coagulation and fibrinolysis were collected before CEA, and the subjects underwent repeated TCD monitoring for MES. A subpopulation (n= 46) underwent MR imaging and repeated neuropsychological examination (preoperative, as well 4 and 100 days after CEA). In MRI, the average apparent diffusion coefficients were higher in the ipsilateral white matter (WM), and altough the interhemispheric difference was abolished by CEA, the levels remained higher than in controls. Symptomatic stenoses were associated with more sluggish perfusion especially in WM, and lower pulsatility of flow in TCD. All patients had poorer cognitive performance than healthy controls. Cognitive functions improved as expected by learning effect despite transient postoperative worsening in a few subjects. Improvement was greater in patients with deepest hypoperfusion, primarily in executive functions. Symptomatic stenoses were associated with higher hematocrit and tissue plasminogen activator antigen levels, as well as higher rate of MES and ulcerated plaques, and better postoperative improvement of vasoreactivity and pulsatility. In light of the findings, carotid stenosis is associated with differences in brain diffusion, perfusion, and cognition. The effect on diffusion in the ipsilateral WM, partially reversible by CEA, may be associated with WM degeneration. Asymptomatic and symptomatic subpopulations differ from each other in terms of hemodynamic adaptation and in their vascular physiological response to removal of stenosis. Although CEA may be associated with a transient cognitive decline, a true improvement of cognitive performance by CEA is possible in patients with the most pronounced perfusion deficits. Mediators of fibrinolysis and unfavourable hemorheology may contribute to the development of a symptomatic disease in patients with a high-grade stenosis.
  • Vikatmaa, Pirkka (Helsingin yliopisto, 2011)
    According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.
  • Sulin, Zackris (1903)
  • Zhou, Binling (2014)
    This thesis is going to do a comparative study of the Nordic Maritime Codes, Chinese Maritime Code and Rotterdam Rules (United Nations Convention on Contract for the International Carriage of Goods Wholly or Partly by Sea) with respect to carrier’s obligations and liabilities imposed hereupon. The backgrounds for this study are the ambitious goals and controversial future of the Rotterdam Rules, the significant roles that the Nordic countries and China have played in international carriage of goods by sea, and the important position of the carrier’s mandatory obligations and liabilities in this field. Through the comparative study, this thesis tries to disclose the similarities and differences between these legal regimes, to see what changes will be brought to the Nordic/Chinese maritime laws and what impact may be led to their shipping industries if they finally accept the Rotterdam Rules. Based on these backgrounds, the detail contents discussed in this thesis include: (1) the legislative history and scope of application; (2) period of carrier’s responsibility; (3) carrier’s obligations; (4) carrier’s liability for physical loss of or damage to the goods; (5) carrier’s liability for delay in delivery; (6) carrier’s liabilities for deviation, deck cargo and live animals. Each of the NMCs, CMC and the Rotterdam Rules is respectively discussed in detail under each part. By comparing the regional solutions and the new international Convention, at the end of this thesis the possible future of the Rotterdam Rules is discussed from Nordic and Chinese perspectives of views.
  • Lönnberg, Stefan (Helsingin yliopisto, 2012)
    The aim of this study was to evaluate the performance and age-specific effectiveness of cervical cancer screening, by focusing on audit studies of the Finnish cervical cancer screening programme within case control designs with information on the outcome of screening. The study also developed further quality assurance protocols for integration into the programme. The coverage and accuracy of diagnostic data in the screening register were evaluated via individual linkage to two other health care registers. Precancerous and cancerous lesions arising in the screened population were used in an audit of cytology wherein screening-test validity in programme service laboratories was evaluated with a focus on sensitivity failures in the form of false negative screening results. Outcome measures were also related to cross-sectional performance indicators, and variations between laboratories were explored. The mode of detection and screening history was determined for every cervical cancer case and cervical cancer death in Finland in 2000 - 2009. Population-based controls were used in estimation of the age-specific effectiveness of the organised programme in a case control design. We were also able to perform age-specific self-selection bias corrections of the effectiveness estimates. The quality of the screening and cancer registers is such that reliable monitoring and also individual case audits are possible. We found that some analytical failures as measured in terms of false-negative rates of case smears do occur in the programme but that their impact on cancer incidence is small. However, the reproducibility of the cytodiagnosis and variations in the specificity of the screening laboratories should be addressed by means of cytology audits and feedback to the screeners. A large proportion of the cervical cancers and most deaths from cervical cancer occur at ages above the currently recommended invitational ages. Only a very small proportion of the burden arises before first invitation. Non-attenders contribute significantly to incidence and mortality, and a smaller proportion of cases can be attributed to screening failures. Management of screening positives appears to be excellent. The effectiveness of screening, as measured by the reduction in the risk of cervical cancer and death from cervical cancer associated with participation in organised screening, was strongly dependent on age. Screening at ages below 40 and, especially, below 30 was associated with a clearly smaller risk reduction than screening at 40 and above. Also the duration of the protective effect was age-dependent. Most cancers and cancer deaths currently occur because of a lack of screening, and not because of low quality of the screening test or management process. Monitoring and audits of the screening programme are clearly important for the programme s development and further optimisation.
  • Snellman, Marja (2007)
    Avohoitokeuhkokuume on vakava sairaus ja yleinen kuolinsyy maailmanlaajuisesti erityisesti ikääntyneiden keskuudessa. Suomessa sen arvioidaan aiheuttavan vuosittain yli 2000 kuolemantapausta yli 65-vuotiaissa. Keuhkokuumeen yleisimpänä taudinaiheuttajana pidetään on Streptococcus pneumoniae -bakteeria, pneumokokkia. Keuhkokuumeen mikrobietiologian selvittäminen on hankalaa, sillä täydellistä kultaista standardia -diagnostista testiä, joka ei anna vääriä positiivisia tai negatiivisia tuloksia- ei ole olemassa. Kansanterveyslaitos on aloittanut keuhkokuumetutkimuksen, jossa pyritään selvittämään keuhkokuumeen yleisyyttä ja aiheuttajia ikäihmisten parissa. Erityisen kiinnostuksen kohteena on pneumokokkibakteerin osuus taudinaiheuttajana. Tutkimukseen osallistuvilta potilailta kerätään yskös- , virtsa-, nenänielu sekä verinäytteitä, jotka analysoidaan käyttäen erilaisia mikrobiologisia menetelmiä. Yksi tutkimuksen päätavoitteista on muodostaa pneumokokkikeuhkokuumeen tapausmäärittely. Tätä varten tarvitaan tietoa tutkimuksessa suoritettujen diagnostisten testien sensitiivisyyksistä ja spesifisyyksistä. Kultaisen standardin puuttuessa testien sensitiivisyyksien ja spesifisyyksien estimointi ei onnistu tavanomaisin menetelmin, sillä tutkittavien yksilöiden todellinen taudin tila on tuntematon. Tässä tutkielmassa käsitellään latentin luokan analyysia diagnostisten testien luotettavuuden ja pneumokokkikeuhkokuumeen prevalenssin arvioimisessa, kun kultainen standardi puuttuu. Menetelmää sovelletaan Kansanterveyslaitoksen keuhkokuumetutkimuksessa kerättyyn aineistoon. Menetelmään liittyvän teorian lisäksi tutkielmassa esitellään estimointia varten R-ohjelmalle kirjoittamani funktio. Tärkeimpiä lähteitä ovat: Agresti, Alan 2002: Categorical Data Analysis. Wiley. New York. Hagenaars, Jacques A. 1990: Categorical Longitudinal Data. Sage Publication. London Formann, A. - Kohlmann, T. 1996: Latent class analysis in medical research. Statistical Methods in Medical Research, 5, 179-211.
  • Snellman, Marja (2007)
    Community-acquired pneumonia (CAP) is a severe disease and a major cause of death worldwide especially among the elderly. The most common causative pathogen is Streptococcus pneumoniae, pneumococcus. The diagnosis of pneumococcal pneumonia is difficult because there is no gold standard, a diagnostic test that would identify all cases and yet be definite. National Public Health Institute has launched a Finnish Community-Acquired Pneumonia study investigating the frequency and causes of CAP among the elderly aged 65 years and above. Sputum, urine, blood and nasopharyngeal swab samples are the collected from the subjects enrolled in the study and a large number of microbiological assays are performed on samples. One of the main objectives is to find a case definition for pneumococcal pneumonia in the elderly. For this purpose, the accuracy of diagnostic tests performed in the study need to be evaluated. In the absence of gold standard, the true disease status of the subjects is latent and the sensitivities and the specificities of the tests cannot be estimated using conventional methods. The aim of this thesis is to to estimate the sensitivities and the specificities of diagnostic tests and estimate the prevalence of pneumococcal pneumonia among the elderly population in Finland using latent class analysis. The method is applied to data collected in the Finnish Community-Acquired Pneumonia study. Methodological issues in latent class analysis are discussed. In addition, a function for estimating the model parameters using statistical program R is presented. The main sources are: Agresti, Alan 2002: Categorical Data Analysis. Wiley. New York. Hagenaars, Jacques A. 1990: Categorical Longitudinal Data. Sage Publication. London Formann, A. - Kohlmann, T. 1996: Latent class analysis in medical research. Statistical Methods in Medical Research, 5, 179-211.
  • Paukkonen, Heli (2013)
    Casein based formulations are promising materials for controlled drug release. Caseins are the major milk proteins, and their biocompatibility, low toxicity and natural metabolism in physiological systems make caseins extremely suitable materials for pharmaceutical formulations. Polyelectrolyte complex nanoparticles can be prepared under very mild conditions, and they are stable in the gastrointestinal tract, which makes them suitable carrier materials for oral delivery and controlled release of peptide and protein drugs. Aim of this work was to synthesize casein-poly(acrylic acid) polyelectrolyte complex nanoparticles in different mass ratios, and to study the release profile of a model compound rhodamine 6G from these nanoparticles. The casein shell of the nanoparticles was crosslinked with two different crosslinkers, because the objective was to study the effect of surface modification on size of nanoparticles as well as on the release profile of the model compound. The goal was to achieve controlled release of the model compound by modifying the thickness and the density of the casein shell structure. Size and size distribution of nanoparticles was studied by dynamic light scattering. Surface charge was studied by electrophoretic mobility measurements. Morphology was characterized with electron microscopy, and the effect of the casein shell thickness on the release of rhodamine 6G was studied with dialysis method. The synthesized nanoparticles had spherical morphology, but the size distribution was wide. The release of rhodamine 6G was slower from the nanoparticles when compared to the release of reference free rhodamine 6G, but the effect of casein shell thickness on the release of loaded rhodamine 6G remained partially unclear. However, it seems possible to achieve controlled release of encapsulated compounds from casein-poly(acrylic acid) nanoparticles with optimal surface modification in the future.
  • Niemelä, Eeva-Leena (2013)
    Tutkielman tarkoituksena on cash pooling –järjestelmien arvioiminen osakeyhtiölain näkökulmasta ja sen selvittäminen, mitä vaatimuksia osakeyhtiölain säännökset asettavat cash pooling –järjestelmille, miten järjestelmät tulisi lainmukaisesti toteuttaa ja mitä seuraamuksia aiheutuu, jos cash pooling –järjestelmät rikkovat osakeyhtiölain säännöksiä. Cash pooling –järjestelmät ovat yleisesti käytössä oleva tapa järjestää konsernin sisäinen kassanhallinta. Osakeyhtiölain näkökulmasta cash pooling –järjestelmissä on käytännössä kyse konsernin sisäisistä velka- ja saamissuhteista, joita arvioidaan yhtiöoikeudellisesti lähipiirilainoina. Lisäksi cash pooling –järjestelmien yhteydessä annetaan usein lähipiirivakuuksia. Lähipiirilainojen ja -vakuuksien laillisuutta osakeyhtiölain näkökulmasta arvioidaan ensisijaisesti yleisten yhtiöoikeudellisten periaatteiden perusteella. Cash pooling –järjestelmien näkökulmasta keskeisimpiä periaatteita ovat OYL 1:5:n yhtiön toiminnan tarkoitus, OYL 1:7:n yhdenvertaisuusperiaate sekä OYL 1:8:n johdon huolellisuusvelvollisuus. Lähipiirilainan ja –vakuuden antamiseen soveltuu myös OYL 13:1.3:n laittoman varojenjaon kielto, joka edellyttää, että lähipiirilainan tai –vakuuden antamiselle on liiketaloudellinen peruste. Cash pooling –järjestelmässä hyväksyttävä liiketaloudellinen peruste voi olla esimerkiksi lähipiirilainan tai –vakuuden antamisesta saatu korkotuotto, vastainen rahoitus, alentuneet pankkikulut tai muu yhtiön saama hyöty. Useimmiten cash pooling –järjestelmät ovat osakeyhtiölain näkökulmasta lähtökohtaisesti ongelmattomia niin kauan, kun kaikki konserniyhtiöt ovat maksukykyisiä. Lähipiirilainan tai –vakuuden antaminen cash pooling –järjestelmän puitteissa on riskialtista erityisesti, jos koko konserni tai joku järjestelmään osallistuvista konserniyhtiöistä on maksuvaikeuksissa. Tällöin cash pooling –järjestelmän sisällä annetut lähipiirilainat tai –vakuudet voivat olla osakeyhtiölain OYL 13:1.3:n perusteella laitonta varojenjakoa sen perusteella, ettei niiden antamiselle ole yhtiön näkökulmasta liiketaloudellista perustetta. Laittoman varojenjaon yhtiöoikeudellisina seuraamuksina voivat tulla kysymykseen oikeustoimen pätemättömyys OYL 6:28:n nojalla, OYL 13:4:n mukainen laittoman varojenjaon palautusvelvollisuus sekä vahingonkorvausvastuun osalta erityisesti yhtiön johtoa koskeva OYL 22:1:n säännös. Lähipiiritransaktioiden kohdalla johdon vahingonkorvausvastuuta on vielä tehostettu OYL 22:1.3:n tuottamusolettamalla.
  • Wiikinkoski, Oskari (2013)
    Ylioppilastutkintolautakunta päätyi laskinohjetta uudistaessaan sallimaan kevään 2012 matematiikan ylioppilaskokeessa ensimmäistä kertaa myös niin kutsuttujen CAS-laskinten käytön. Tämä uudistus johti tilanteeseen, jossa osa pitkän matematiikan kokeen tehtävistä oli mahdollista ratkaista pelkästään laskimen avulla. Matematiikan opettajat ovat ilmaisseet huolensa laskinten käytön tuomista haasteista ja uhkista matematiikan opiskelulle ja opetukselle lukiossa sekä myös matematiikan tulevaisuudelle oppiaineena. Tässä tutkielmassa perehdytään teknisten apuvälineiden, erityisesti CAS-laskinten, käytön vaikutuksiin matematiikan opiskelussa sekä opettajien näkemyksiin ja odotuksiin siitä, miten laskimet tulevat muuttamaan lukion matematiikan opetusta ja ylioppilaskoetta. Matematiikan opettajien keskuudessa on herännyt kriittinen keskustelu uusien apuvälineiden käytöstä ja erityisesti CAS-laskinten antamasta edusta pitkän matematiikan ylioppilaskokeessa. Tässä tutkielmassa käydään läpi kevään 2013 pitkän matematiikan kokeen tehtäviä, ja pohditaan millaisen edun CAS-laskinta käyttävä ylioppilaskokelas saa sellaiseen opiskelijatoveriinsa verrattuna, jolla on käytössään tavallinen graafinen laskin ja taulukkokirja. Tehtävien ratkaisuja lähestytään konstruktivistisen oppimiskäsityksen ja -ratkaisuprosessin näkökulmasta. Ratkaisujen lopuksi pohditaan tulevatko ylioppilaskokelaan taidot mitatuksi tehtävän tarkoittamalla tavalla, jos kokelaalla on käytössään uusimmat tekniset apuvälineet. Lisäksi tutkielmassa esitellään mahdollisuuksia hyödyntää CAS-laskinta pitkän matematiikan opetuksen apuvälineenä ja tehdään katsaus saatavilla oleviin matematiikan ohjelmistoihin. Tutkielmassa käydään läpi myös Matemaattisten aineiden opettajien liiton keväällä 2012 tekemän CAS-laskimia koskevan kyselytutkimuksen tuloksia pohjustuksena laskimista käytävälle keskustelulle. Tutkielman tuloksena todettiin, että opettajakunta on jossain määrin kahtiajakautunut suhteessa teknisten apuvälineiden, erityisesti CAS-laskinten, käyttöön matematiikan opetuksen tukena. Yleinen vallitseva mielipide opettajien keskuudessa oli, että ainakin ylioppilaskokeen tehtäviä täytyy miettiä uudelleen, jos CAS-laskinten käyttö aiotaan sallia myös jatkossa. Jopa koko matematiikan kokeen uudistamista ehdotettiin. Tätä näkemystä tukevat myös tässä tutkielmassa pitkän matematiikan tehtävien ratkaisuista saadut kokemukset. Osa kokeen tehtävistä menetti jossain määrin merkityksensä, kun niiden ratkaisemiseen käytettiin apuvälineenä CAS-laskinta. Tutkielmassa havaittiin, että on silti mahdollista luoda myös sellaisia koetehtäviä, jotka edelleen mittaavat ylioppilaskokelaan matemaattisia taitoja luotettavasti.
  • Hotti, Anneli (Helsingin yliopisto, 2000)
  • Koivistoinen, Outi (Helsingin yliopisto, 2013)
    The use of metabolic engineering as a tool for production of biochemicals and biofuels requires profound understanding of cell metabolism. The pathways for the most abundant and most important hexoses have already been studied quite extensively but it is also important to get a more complete picture of sugar catabolism. In this thesis, catabolic pathways of L-rhamnose and D-galactose were studied in fungi. Both of these hexoses are present in plant biomass, such as in hemicellulose and pectin. Galactoglucomannan, a type of hemicellulose that is especially rich in softwood, is an abundant source of D-galactose. As biotechnology is moving from the usage of edible and easily metabolisable carbon sources towards the increased use of lignocellulosic biomass, it is important to understand how the different sugars can be efficiently turned into valuable biobased products. Identification of the first fungal L-rhamnose 1-dehydrogenase gene, which codes for the first enzyme of the fungal catabolic L-rhamnose pathway, showed that the protein belongs to a protein family of short-chain alcohol dehydrogenases. Sugar dehydrogenases oxidising a sugar to a sugar acid are not very common in fungi and thus the identification of the L-rhamnose dehydrogenase gene provides more understanding of oxidative sugar catabolism in eukaryotic microbes. Further studies characterising the L-rhamnose cluster in the yeast Scheffersomyces stipitis including the expression of the L-rhamnonate dehydratase in Saccharomyces cerevisiae finalised the biochemical characterisation of the enzymes acting on the pathway. In addition, more understanding of the regulation and evolution of the pathway was gained. D-Galactose catabolism was studied in the filamentous fungus Aspergillus niger. Two genes coding for the enzymes of the oxido-reductive pathway were identified. Galactitol dehydrogenase is the second enzyme of the pathway converting galactitol to L-xylo-3-hexulose. The galactitol dehydrogenase encoding gene ladB was identified and the deletion of the gene resulted in growth arrest on galactitol indicating that the enzyme is an essential part of the oxido-reductive galactose pathway in fungi. The last step of this pathway converts D-sorbitol to D-fructose by sorbitol dehydrogenase encoded by sdhA gene. Sorbitol dehydrogenase was found to be a medium chain dehydrogenase and transcription analysis suggested that the enzyme is involved in D-galactose and D-sorbitol catabolism.   The thesis also demonstrates how the understanding of cell metabolism can be used to engineer yeast to produce glycolic acid. Glycolic acid is a chemical, which can be used for example in the cosmetic industry and as a precursor for biopolymers. Currently, glycolic acid is produced by chemical synthesis in a process requiring toxic formaldehyde and fossil fuels. Thus, a biochemical production route would be preferable from a sustainability point of view. Yeasts do not produce glycolic acid under normal conditions but it is a desired production host for acid production because of its natural tolerance to low pH conditions. As a proof of concept, pure model substrates, e.g. D-xylose and ethanol, were used as starting materials for glycolic acid production but the knowledge can be further applied to an expanded substrate range such as biomass derived sugars. Already the introduction of a heterologous glyoxylate reductase gene resulted in glycolic acid production in the yeasts S. cerevisiae and Kluyveromyces lactis. Further modifications of the glyoxylate cycle increased the production of glycolic acid and it was successfully produced in bioreactor cultivation. The challenge of biotechnology is to produce high value products from cheap raw materials in an economically feasible way. This thesis gives more basic understanding to the topic in the form of new information regarding L-rhamnose and D-galactose metabolism in eukaryotic microbes as well as provides an example on how cell metabolism can be engineered in order to turn the cell into a cell factory that is able to produce a useful chemical.
  • Sibaouih, Ahlam (Helsingin yliopisto, 2015)
    Catalytic transformation of carbon dioxide into useful organic compounds has attracted much attention due to its economic and environmental benefits. In addition, other reasons are also taken into account, such as the possible utilization of CO2 as a renewable source chemical and the growing concern of the greenhouse effect. CO2 is an abundant, cheap, and safe C1 building block in organic synthesis. However, due to the inert nature of CO2, efficient catalytic processes of its chemical fixation remain a significant challenge. In this work, we have studied a possible pathway for practical utilization of CO2. The reaction of CO2 with epoxides giving cyclic carbonates, has been investigated. New catalyst systems based on cobalt capable of catalyzing the chemical transformation of carbon dioxide are described in detail. Oxygen is a cheap, readily available and environmentally friendly natural oxidant. The catalytic activation of molecular oxygen has great potential in a variety of applications. Catalysis and reactions, which are based on molecular oxygen, can also be considered to be ecologically benign processes. Moreover, catalytic reactions in water are highly desirable in terms of green chemistry. In this context, our purpose was to develop an environmentally friendly catalytic systems, suitable for oxidation of alcohols with molecular oxygen in water solution. In this part of the work, efficient catalysts, based on copper complexes have been synthesized and studied in the presence of TEMPO for the oxidation of benzyl and aliphatic alcohols with molecular oxygen in aqueous and nonaqueous medium.
  • Hakola, Maija (Helsingin yliopisto, 2013)
    There is nowadays a strong concern about decreasing oil supplies and global warming leading to ever increasing interest in biobased fuels and chemical production. The utilization of lignocellulosic raw materials for liquid biofuels and chemicals is a challenging task due to raw materials rigid structure which is resistant towards any actions to break it. Thus the raw materials should be pretreated to reach an economically vital process. Catalytic and alkaline oxidation presented here are novel, highly selective and effective methods to separate carbohydrates from lignin in different lignocellulosic materials. Both pretreatment methods are carried out at 120 140 ˚C for 4 20 hours under 10 bar oxygen pressure and in alkaline water solution. In catalytic oxidation also copper(II) phenanthroline catalyst is used. The obtained carbohydrate rich fraction is remarkably easy to hydrolyze with enzymes to corresponding sugars. The carbohydrate rich material from catalytic oxidation is nearly quantitatively converted into corresponding monohydrates in 24 hours by enzymatic hydrolysis. The enzyme loading can also be significantly decreased compared to standard methods, which helps to decrease the total costs of the process. Catalytic and alkaline oxidation pretreatment methods can be applied also to chromated copper arsenite treated waste wood, which is considered as hazardous waste. When combined with very mild sulfuric acid extraction and enzymatic hydrolysis 90 % sugar yield is obtained from the carbohydrate material. The sugars can be further utilized in chemical industry, which makes this method an interesting way to recycle hazardous waste. In a process turning lignocellulosic materials into sugars hydrolysis plays the key role. The hydrolysis is usually carried out enzymatically or with acids. They both have their disadvantages, such as long reaction times, poor yields or corrosive effect. As an alternative to traditional acid hydrolysis a microwave assisted mild acid hydrolysis is presented here. It can be applied to xylan, which is converted to xylose quantitatively in just one minute with 2 wt-% hydrochloric acid. When applied to milled birch wood 70 % yield of xylose is obtained. Subjecting alkaline oxidation pretreated birch to a three-step reaction, all the xylan and 66 % of the cellulose is hydrolyzed to corresponding sugars.
  • Nurttila, Sandra (2013)
    Lignocellulosic biomass has received widespread attention as environmentally benign feedstock for fuels. Biomass consists of cellulose, hemicellulose and lignin and has rather high oxygen content. Different techniques for the conversion of lignocellulose to liquid fuels have been suggested in the literature. In this thesis the emphasis is on the utilization of biomass-derived platform molecules. Platform molecules include eg. ketones, alcohols and carboxylic acids. In the literary section different deoxygenation and C-C coupling reactions for the conversion of biomass-derived platform molecules to larger hydrocarbons have been reviewed. Reaction routes for upgrading of the platform molecules 5-hydroxymethylfurfural, 2-furaldehyde, levulinic acid and some monofunctional compounds have been presented. These paths comprise mainly dehydration, hydrogenation, aldol condensation and ketonization. Heterogeneous catalysis, particularly bifunctional supported catalysts, dominates in this field. The selectivity that may be achieved with homogeneous catalysts is seen as highly desirable and served as the main incentive for the experimental work. Furthermore, the lack of publications in the area of homogeneously catalyzed C-C coupling of biomass-derived compounds also motivated for the work. Herein, 1st row transition metal acetates were utilized as catalysts for the ketonization of biomass-derived levulinic acid and other carboxylic acids. Some experiments were conducted with lignin as well. Reactions were performed under microwave heating or reflux conditions. Products were analyzed by GC-MS, GC-FID, NMR and FTIR. Combinatorial chemistry made it possible to conduct up to twelve reactions simultaneously. More than 160 reactions were performed in less than two months' time. The main product in many of the reactions was aromatic phthalic acid mono 2-ethylhexyl ester. Some other interesting products included hexadecanoic acid, 2,6-dimethyl-2,5-heptadien-4-one, diisooctyl and dibutyl phthalate. Despite small amounts of the products, their presence proves that various compounds may be produced from biomass by tailoring the catalyst and reaction conditions.
  • Kambur, Oleg (Helsingin yliopisto, 2013)
    Acute pain is an important warning signal, however, neuropathic pain and often chronic pain,lack a physiological function. Pain is a major clinical challenge and especially chronic and neuropathic pain are difficult to treat. On individual level, pain causes occupational and functional disability, suffering, and impairs quality of life. On a macro level pain and its direct and indirect consequences cause multi-billion expenses. Genetic factors and mechanisms underlying susceptibility to chronic pain have recently raised significant scientific interest. COMT-gene, which codes for catechol-O-methyltransferase (COMT), is subject for genetic polymorphic variation and COMT polymorphisms modulate pain and opioid analgesia in humans. The effects of COMT on pain and opioid responses were studied in rodents and humans. In mice, COMT deficiency was associated with altered stress- and morphine-induced analgesia reflecting weakened capacity of endogenous pain modulation and changes in opioidergic transmission. In normal mice, COMT inhibitors reduced thresholds of mechanical nociception and shortened thermal nociceptive latencies and thus increased nociceptive sensitivity in models of acute and inflammatory pain. Pronociceptive effects were COMT-dependent. In the spinal nerve ligation model of neuropathic pain in rats nitecapone decreased nociceptive symptoms - cold and mechanical hyperalgesia and allodynia. In humans, genetic variation of COMT gene was associated with pain phenotypes. The associations were strongest for the experimental pain phenotypes but also clinical pain phenotypes, such as acute postoperative pain, showed associations (uncorrected p=0.006-0.007)with three single nucleotide polymorphisms (SNPs). The strongest effect was observed in the SNP located in the 3´UTR-region of COMT, rs887200, pointing to importance of this region in regulation of nociceptive phenotypes and confirming the results in rodents. Together, these results confirm the role of COMT in pain and opioid responses. The antiallodynic effects of COMT inhibitors should be further studied in neuropathic pain since the safety and efficacy of current therapies are not satisfactory. In humans, mutations in COMT gene affect pain. The predictive value of individual SNPs, however, is limited and several SNPs of COMT as well as other genetic factors should be included in the same analysis or treatment algorithms possibly utilizing a haplotypic approach. Finally, the effects of most SNPs associated with pain phenotypes on COMT expression and activity are not known and should be explored in further studies.
  • Hyvärinen, Otto (Helsingin yliopisto, 2011)
    In meteorology, observations and forecasts of a wide range of phenomena for example, snow, clouds, hail, fog, and tornados can be categorical, that is, they can only have discrete values (e.g., "snow" and "no snow"). Concentrating on satellite-based snow and cloud analyses, this thesis explores methods that have been developed for evaluation of categorical products and analyses. Different algorithms for satellite products generate different results; sometimes the differences are subtle, sometimes all too visible. In addition to differences between algorithms, the satellite products are influenced by physical processes and conditions, such as diurnal and seasonal variation in solar radiation, topography, and land use. The analysis of satellite-based snow cover analyses from NOAA, NASA, and EUMETSAT, and snow analyses for numerical weather prediction models from FMI and ECMWF was complicated by the fact that we did not have the true knowledge of snow extent, and we were forced simply to measure the agreement between different products. The Sammon mapping, a multidimensional scaling method, was then used to visualize the differences between different products. The trustworthiness of the results for cloud analyses [EUMETSAT Meteorological Products Extraction Facility cloud mask (MPEF), together with the Nowcasting Satellite Application Facility (SAFNWC) cloud masks provided by Météo-France (SAFNWC/MSG) and the Swedish Meteorological and Hydrological Institute (SAFNWC/PPS)] compared with ceilometers of the Helsinki Testbed was estimated by constructing confidence intervals (CIs). Bootstrapping, a statistical resampling method, was used to construct CIs, especially in the presence of spatial and temporal correlation. The reference data for validation are constantly in short supply. In general, the needs of a particular project drive the requirements for evaluation, for example, for the accuracy and the timeliness of the particular data and methods. In this vein, we discuss tentatively how data provided by general public, e.g., photos shared on the Internet photo-sharing service Flickr, can be used as a new source for validation. Results show that they are of reasonable quality and their use for case studies can be warmly recommended. Last, the use of cluster analysis on meteorological in-situ measurements was explored. The Autoclass algorithm was used to construct compact representations of synoptic conditions of fog at Finnish airports.
  • Partanen, Sanna (Helsingin yliopisto, 2006)
    Cathepsin D (CTSD) is a lysosomal protease, the deficiency of which is fatal and associated with neurodegeneration. CTSD knock-out mice, which die at the age of four weeks, show intestinal necrosis, loss of lymphoid cells and moderate pathological changes in the brain. An active-site mutation in the CTSD gene underlies a neurodegenerative disease in newborn sheep, characterized by brain atrophy without any changes to visceral tissues. The CTSD deficiences belong to the group of neuronal ceroid-lipofuscinoses (NCLs), severe neurodegenerative lysosomal storage disorders. The aim of this thesis was to examine the molecular and cellular mechanisms behind neurodegeneration in CTSD deficiency. We found the developmental expression pattern of CTSD to resemble that of synaptophysin and the increasing expression of CTSD to coincide with the active period of myelination in the rat brain, suggesting a role for CTSD in early rat brain development. An active-site mutation underlying the congenital ovine NCL not only affected enzymatic activity, but also changed the stability, processing and transport of the mutant protein, possibly contributing to the disease pathogenesis. We also provide CTSD deficiency as a first molecular explanation for human congenital NCL, a lysosomal storage disorder, characterized by neuronal loss and demyelination in the central nervous system. Finally, we show the first evidence for synaptic abnormalities and thalamocortical changes in CTSD-deficient mice at the molecular and ultrastructural levels. Keywords: cathepsin D, congenital, cortex, lysosomal storage disorder, lysosome, mutation, neurodegeneration, neuronal ceroid-lipofuscinosis, overexpression, synapse, thalamus