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  • Volotinen, Marjo (Helsingin yliopisto, 2009)
    Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.
  • Alakuijala, Anniina (Helsingin yliopisto, 2007)
    γ-aminobutyric acid (GABA) is the main inhibitory transmitter in the nervous system and acts via three distinct receptor classes: A, B, and C. GABAC receptors are ionotropic receptors comprising ρ subunits. In this work, we aimed to elucidate the expression of ρ subunits in the postnatal brain, the characteristics of ρ2 homo-oligomeric receptors, and the function of GABAC receptors in the hippocampus. In situ hybridization on rat brain slices showed ρ2 mRNA expression from the newborn in the superficial grey layer of the superior colliculus, from the first postnatal week in the hippocampal CA1 region and the pretectal nucleus of the optic tract, and in the adult dorsal lateral geniculate nucleus. Quantitative RT-PCR revealed expression of all three ρ subunits in the hippocampus and superior colliculus from the first postnatal day. In the hippocampus, ρ2 mRNA expression clearly dominated over ρ1 and ρ3. GABAC receptor protein expression was confirmed in the adult hippocampus, superior colliculus, and dorsal lateral geniculate nucleus by immunohistochemistry. From the selective distribution of ρ subunits, GABAC receptors may be hypothesized to be specifically involved in aspects of visual image motion processing in the rat brain. Although previous data had indicated a much higher expression level for ρ2 subunit transcripts than for ρ1 or ρ3 in the brain, previous work done on Xenopus oocytes had suggested that rat ρ2 subunits do not form functional homo-oligomeric GABAC receptors but need ρ1 or ρ3 subunits to form hetero-oligomers. Our results demonstrated, for the first time, that HEK 293 cells transfected with ρ2 cDNA displayed currents in whole-cell patch-clamp recordings. Homomeric rat ρ2 receptors had a decreased sensitivity to, but a high affinity for picrotoxin and a marked sensitivity to the GABAC receptor agonist CACA. Our results suggest that ρ2 subunits may contribute to brain function, also in areas not expressing other ρ subunits. Using extracellular electrophysiological recordings, we aimed to study the effects of the GABAC receptor agonists and antagonists on responses of the hippocampal neurons to electrical stimulation. Activation of GABAC receptors with CACA suppressed postsynaptic excitability and the GABAC receptor antagonist TPMPA inhibited the effects of CACA. Next, we aimed to display the activation of the GABAC receptors by synaptically released GABA using intracellular recordings. GABA-mediated long-lasting depolarizing responses evoked by high-frequency stimulation were prolonged by TPMPA. For weaker stimulation, the effect of TPMPA was enhanced after GABA uptake was inhibited. Our data demonstrate that GABAC receptors can be activated by endogenous synaptic transmitter release following strong stimulation or under conditions of reduced GABA uptake. The lack of GABAC receptor activation by less intensive stimulation under control conditions suggests that these receptors are extrasynaptic and activated via spillover of synaptically released GABA. Taken together with the restricted expression pattern of GABAC receptors in the brain and their distinctive pharmacological and biophysical properties, our findings supporting extrasynaptic localization of these receptors raise interesting possibilities for novel pharmacological therapies in the treatment of, for example, epilepsy and sleep disorders.
  • Mykkänen, Anna (Helsingin yliopisto, 2011)
    Monocarboxylate transporters (MCTs) transport lactate and protons across cell membranes. During intense exercise, lactate and protons accumulate in the exercising muscle and are transported to the plasma. In the horse, MCTs are responsible for the majority of lactate and proton removal from exercising muscle, and are therefore also the main mechanism to hinder the decline in pH in muscle cells. Two isoforms, MCT1 and MCT4, which need an ancillary protein CD147, are expressed in equine muscle. In the horse, as in other species, MCT1 is predominantly expressed in oxidative fibres, where its likely role is to transport lactate into the fibre to be used as a fuel at rest and during light work, and to remove lactate during intensive exercise when anaerobic energy production is needed. The expression of CD147 follows the fibre type distribution of MCT1. These proteins were detected in both the cytoplasm and sarcolemma of muscle cells in the horse breeds studied: Standardbred and Coldblood trotters. In humans, training increases the expression of both MCT1 and MCT4. In this study, the proportion of oxidative fibres in the muscle of Norwegian-Swedish Coldblood trotters increased with training. Simultaneously, the expression of MCT1 and CD147, measured immunohistochemically, seemed to increase more in the cytoplasm of oxidative fibres than in the fast fibre type IIB. Horse MCT4 antibody failed to work in immunohistochemistry. In the future, a quantitative method should be introduced to examine the effect of training on muscle MCT expression in the horse. Lactate can be taken up from plasma by red blood cells (RBCs). In horses, two isoforms, MCT1 and MCT2, and the ancillary protein CD147 are expressed in RBC membranes. The horse is the only species studied in which RBCs have been found to express MCT2, and the physiological role of this protein in RBCs is unknown. The majority of horses express all three proteins, but 10-20% of horses express little or no MCT1 or CD147. This leads to large interindividual variation in the capacity to transport lactate into RBCs. Here, the expression level of MCT1 and CD147 was bimodally distributed in three studied horse breeds: Finnhorse, Standardbred and Thoroughbred. The level of MCT2 expression was distributed unimodally. The expression level of lactate transporters could not be linked to performance markers in Thoroughbred racehorses. In the future, better performance indexes should be developed to better enable the assessment of whether the level of MCT expression affects athletic performance. In human subjects, several mutations in MCT1 have been shown to cause decreased lactate transport activity in muscle and signs of myopathy. In the horse, two amino acid sequence variations, one of which was novel, were detected in MCT1 (V432I and K457Q). The mutations found in horses were in different areas compared to mutations found in humans. One mutation (M125V) was detected in CD147. The mutations found could not be linked with exercise-induced myopathy. MCT4 cDNA was sequenced for the first time in the horse, but no mutations could be detected in this protein.
  • Baral, Bikash (Helsingin yliopisto, 2015)
    Phytopathogens, notably Heterobasidion annosum, evolved several strategical combinations to infect and subsequently colonize their host even under different stress conditions. Fungal ABC transporters are well-known defenses that can confer resistance against host-secreted secondary metabolites by transporting them outside of the fungal cells and thus keeping their intracellular concentration low. Here, we aim to unveil the evolutionary trajectories of total ABC transporters-encoding genes in Heterobasidion annosum. The gene expression pattern was monitored with the fungus subjected to different chemical stressors and during fungal growth on wood. We identified 32 putative ABC protein-encoding genes in the Heterobasidion genome. Altogether 20 putative ABC transporter-encoding genes of H. annosum were further analyzed and it was revealed that several genes were either up or downregulated, while some were not differentially expressed under the experimental conditions. The results obtained from the gene expression analysis revealed that an ABC gene (annotated as Ha.ABC-G1 or Hetan_66124), was highly up-regulated in most conditions. This particular transporter-encoding gene (Hetan_66124) with induction level of up to 47 –fold (in heartwood and similar levels in other conditions) was traced, PCR amplified, cloned in Escherichia coli and expression of recombinant protein performed using Saccharomyces cerevisiae as platform. Several experiments aiming to dissect functional roles of this hypothetical protein were performed. The growth of the yeast transformant over expressing the recombinant ABC protein in different terpenoids and weak organic acids were monitored. The growth rate of clones with and without transporters were not significantly different when cultured in plates (SC·gal-ura-) that were exposed to the volatile compounds (limonene, carene and ?-pinene). Based on our findings, we concluded that the yeast transformants carrying the H. annosum ABC-G1 transporter encoding gene do not show increased resistance or tolerance against the monoterpenes. The results of the transcript profiling have further contributed to our understanding about gene expression during fungal colonization upon exposure to chemical stressors. However, further studies are needed in order to specifically unveil the functional roles of these efflux pumps that underlie their transport mechanism with response to the host secreted secondary metabolites.
  • Kaipio, Mikko Ari Ilmari (2014)
    This master’s thesis consists of two parts related to atomic layer deposition (ALD) processes: a literature survey of so-called ex situ in vacuo analysis methods used in investigations of the ALD chemistry and a summary of the work performed by the author using in situ methods. The first part of the thesis is divided into four sections. In the first two sections ALD as a thin film deposition method is introduced, and in situ and ex situ in vacuo publications related to ALD are summarized. The third section is a general overview of ex situ in vacuo analysis methods, and the final section a literature review covering publications where ex situ in vacuo techniques have been employed in studying ALD processes, with a strong emphasis on analysis methods which are based on the use of x-rays. The second part of the thesis consists of in situ quartz crystal microbalance and quadrupole mass spectrometry studies of the V(NEtMe)4/D2O, V(NEtMe)4/O3, Mg(thd)2/TiF4 and Cu2(CH3COO)4/D2O ALD processes. The experimental apparatus and related theory are given a brief overview, followed by a presentation and discussion of the results.
  • Franchin, Alessandro (Helsingin yliopisto, 2015)
    This thesis focuses on the experimental characterization of secondary atmospheric nanoparticles and ions during their formation. This work was developed in two distinct and complementary levels: a scientific level, aimed to advance the understanding of particle formation and a more technical level, dedicated to instrument development and characterization. Understanding and characterizing aerosol formation, is important, as formation of aerosol particles from precursor gases is one of the main sources of atmospheric aerosols. Elucidating how aerosol formation proceeds in detail is critical to better quantify aerosol contribution to the Earth's radiation budget. Experimentally characterizing the first steps of aerosol formation is the key to understanding this phenomenon. Developing and characterizing suitable instrumentation to measure clusters and ions in the sub 3 nm range, where aerosol formation starts, is necessary to clarify the processes that lead to aerosol formation. This thesis presents the results of a series of experimental studies of sub 3 nm aerosol particles and ions. It also shows the results of the technical characterization and instrument development that were made in the process. Specifically, we describe three scientific results achieved from chamber experiments. Firstly the relative contributions of sulfuric acid, ammonia and ions in nucleation processes was quantified experimentally, supporting that sulfuric acid alone cannot explain atmospheric observation of nucleation rates. Secondly, the chemical composition of cluster ions was directly measured for a ternary system, where sulfuric acid, ammonia and water were the condensable vapors. In these measurements we observed a decreasing acidity of the clusters with increasing concentration of gas phase ammonia, with the ratio of sulfuric acid/ammonia staying closer to that of ammonium bisulfate than to that of ammonium sulfate. Finally, in a series of chamber experiments the ion ion recombination coefficient was quantified at different conditions. The ion ion recombination coefficient is a basic physical quantity for modeling ion induced and ion mediated nucleation. We observed a steep increase in the ion ion recombination coefficient with decreasing temperatures and with decreasing relative humidity. This thesis also reviews technical results of: 1) laboratory verification, characterization and testing of different aerosol and ion instruments measuring in the sub 3 nm range; 2) the development of new inlets for such instruments to improve the detection of sub-3 nm particles and ions.
  • Nordbo, Annika (Helsingin yliopisto, 2012)
    Surface-atmosphere exchange of momentum, energy and atmospheric constituents affects the atmosphere--from alterations in local microclimates and mesoscale weather to climate modification. These exchange processes can be studied using direct eddy-covariance (EC) measurements of vertical turbulent transport, but the technique has not yet readily been applied in non-prevailing ecosystems. Thus, the aim of this thesis is to extend the applicability of the EC technique in two ways: to non-standard sites and by further developing the technique itself. To reach the aim, EC measurements over a boreal lake and three urban sites in Helsinki were performed. Long-term measurements over a lake revealed that the water below the thermocline was decoupled from the atmosphere and thus not important for atmospheric vertical turbulent fluxes. The energy exchange between the lake and the atmosphere departs from vegetated surfaces especially due to large nocturnal evaporation fuelled by lake-water heat storage. Long-term measurements at a semi-urban site in Helsinki showed that the surface-atmosphere exchange is altered by anthropogenic activity: changes in surface-cover and an additional anthropogenic heat release (13 W m-2) led to an altered surface energy balance, and anthropogenic CO2 emissions led to a large positive annual CO2 balance (1.8 kg C m-2). Intra-site and intra-city variation in surface-cover led to differences in atmospheric stability and CO2 emissions. The EC technique evaluation demonstrated that (i) the 'energy imbalance problem' in EC measurements is not primarily surface-cover dependent, and that (ii) common calculation errors in EC calculations can be almost 30% of the flux. Water vapour flux measurements with a closed-path analyser were affected by sorption: the signal's arrival is delayed and it is attenuated. A new spectral-correction method based on wavelet analysis was developed to automatically correct for this signal attenuation of constituents. The conclusions of this thesis improve the understanding of surface-atmosphere exchange over non-standard ecosystems. The lake measurements will continue to be used for improving weather forecasts, and the results from the urban studies can be used in city-planning. The EC technique is developed by offering guidance in calculations at urban sites and by introducing a new correction algorithm.
  • Rissanen, Olli (2014)
    Delivering more value to the customer is the goal of every software company. In modern software business, delivering value in real-time requires a company to utilize real-time deployment of software, data-driven decisions and empirical evaluation of new products and features. These practices shorten the feedback loop and allow for faster reaction times, ensuring the development is focused on features providing real value. This thesis investigates practices known as continuous delivery and continuous experimentation as means of providing value for the customers in real-time. Continuous delivery is a development practice where the software functionality is deployed continuously to customer environment. This process includes automated builds, automated testing and automated deployment. Continuous experimentation is a development practice where the entire R\&D process is guided by conducting experiments and collecting feedback. As a part of this thesis, a case study is conducted in a medium-sized software company. The research objective is to analyze the challenges, benefits and organizational aspects of continuous delivery and continuous experimentation in the B2B domain. The data is collected from interviews conducted on members of two teams developing two different software products. The results suggest that technical challenges are only one part of the challenges a company encounters in this transition. For continuous delivery, the company must also address challenges related to the customer and procedures. The core challenges are caused by having multiple customers with diverse environments and unique properties, whose business depends on the software product. Some customers also require to perform manual acceptance testing, which slows down production deployments. For continuous experimentation, the company also has to address challenges related to the customer and organizational culture. An experiment which reveals value for a single customer might not reveal as much value for other customers due to unique properties in each customers business. Additionally, the speed by which experiments can be conducted is relative to the speed by which production deployments can be made. The benefits found from these practices support the case company in solving many of its business problems. The company can expose the software functionality to the customers from an earlier stage, and guide the product development by utilizing feedback and data instead of opinions.
  • Vazquez Muiños, Henrique (2016)
    In this thesis we consider an extension of the Standard Model (SM) with a SU(2) symmetric Dark Sector, and study its viability as a dark matter (DM) model. In the dark sector, a hidden Higgs mechanism generates three massive gauge bosons, which are the DM candidates of the model. We allow a small coupling between the SM Higgs and the scalar of the dark sector, such that there is a scalar mixing. We study the new interactions in the model and analyse the consequences of the scalar mixing: new possible decays of the Higgs into DM, Higgs decay rates and production cross sections different from SM predictions, and possible interactions between DM and normal matter. We study the evolution of the DM abundance from the early universe to the present and compare the relic densities that the model yields with the experimental value measured by the Planck satellite. We compute the decay rates for the Higgs in the model and test if they are consistent with the experimental data from Atlas, CMS and Tevatron. We calculate the cross section for the interaction between DM and normal matter and compare it with the data from the latest direct detection experiments LUX and XENON100. We discuss the impact of the experimental constraints on the parameter space of the model, and find the regions that give the best fit to the experimental data. In this work we show that the agreement with the experiments is optimal when both the DM candidates and the dark scalar are heavier than the Higgs boson.
  • Eklund, Max Julius (2013)
    Abstract The importance of universities providing quality-assurance schemes has increased during the last two decades due to, among other things, an increased tendency in public administration to use evaluations as a tool to enhance efficiency and the changed nature of the state-university relationship. Moreover, we can witness an increased integration of European higher education. Also Finnish higher education has been exposed to these trends and external evaluation and quality assurance systems has become a recurring phenomenon. The objective of this research was to analyse organizational responses at universities to the demand of showing a QA-scheme, and to increase understanding on the role of audits in relation to national and supranational developments, from a perspective of organizational intuitionalism. In so doing, attention is put on what kinds of effects and practices a national form of evaluation has, if compared at the organizational level of two universities. The methodological approach builds on insights from qualitative methods, new-institutional theory and organizational institutionalism. The empirical materials used consisted of documents and half-structured interviews. The interviews were transcribed and analysed through the creation of reference codes in the program ATLAS TI. The reference codes were created according to logics of analytic coding. In the research, four core themes were witnessed. First, in implementing processes or reforms that might be perceived critically in universities, the role of commitment and semantics become of high importance, as does a degree of hierarchy. Second, responding to the demand of showing a quality assurance-scheme and succeeding in audits are not seen to be of high importance by university leadership in that only scarce resources were allocated to the exercise. Third, developing the QA-system was clearly accepted to be a response to European developments but this is hardly an instrument for governance that the Ministry of Education would value in comparison to other instruments. Finally, the recommendations made by the audit teams are not as neutral as they seem, in that they do define what the Universities should accomplish. However, the loosely coupled structure has in many ways lessened many of the impacts and recommendation gained from the audits.
  • Paasonen, Lauri (Helsingin yliopisto, 2010)
    Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.
  • Weckroth, Miina (Helsingin yliopisto, 2004)
  • Soinne, Helena (Helsingin yliopisto, 2009)
    The quantification and characterisation of soil phosphorus (P) is of agricultural and environmental importance and different extraction methods are widely used to asses the bioavailability of P and to characterize soil P reserves. However, the large variety of extractants, pre-treatments and sample preparation procedures complicate the comparison of published results. In order to improve our understanding of the behaviour and cycling of P in soil, it is crucial to know the scientific relevance of the methods used for various purposes. The knowledge of the factors affecting the analytical outcome is a prerequisite for justified interpretation of the results. The aim of this thesis was to study the effects of sample preparation procedures on soil P and to determine the dependence of the recovered P pool on the chemical nature of extractants. Sampling is a critical step in soil testing and sampling strategy is dependent on the land-use history and the purpose of sampling. This study revealed that pre-treatments changed soil properties and air-drying was found to affect soil P, particularly extractable organic P, by disrupting organic matter. This was evidenced by an increase in the water-extractable small-sized (<0.2 µm) P that, at least partly, took place at the expense of the large-sized (>0.2 µm) P. However, freezing induced only insignificant changes and thus, freezing can be taken to be a suitable method for storing soils from the boreal zone that naturally undergo periodic freezing. The results demonstrated that chemical nature of the extractant affects its sensitivity to detect changes in soil P solubility. Buffered extractants obscured the alterations in P solubility induced by pH changes; however, water extraction, though sensitive to physicochemical changes, can be used to reveal short term changes in soil P solubility. As for the organic P, the analysis was found to be sensitive to the sample preparation procedures: filtering may leave a large proportion of extractable organic P undetected, whereas the outcome of centrifugation was found to be affected by the ionic strength of the extractant. Widely used sequential fractionation procedures proved to be able to detect land-use -derived differences in the distribution of P among fractions of different solubilities. However, interpretation of the results from extraction experiments requires better understanding of the biogeochemical function of the recovered P fraction in the P cycle in differently managed soils under dissimilar climatic conditions.
  • Nykänen, Tina (2013)
    Rhazya stricta Decne. är en liten vintergrön buske som hör till familjen Apocynaceae. Den växer i Sydasien och Mellanöstern och används där i traditionell läkekonst. Växtens alla delar används i olika typer av preparat och bland de varierande användningsändamålen finns vård av infektioner, tarmsjukdomar, klåda och diabetes. R. stricta syntetiserar ett hundratal alkaloider varav endast en bråkdel har studerats närmare. Några av de analyserade alkaloiderna har visat sig ha intressanta farmakologiska egenskaper, så som antimikrobiella och cytotoxiska egenskaper. Då det ofta är både ekonomiskt och ekologiskt ohållbart att odla eller samla stora mängder medicinalväxter från naturen, har man utvecklat cellodlingar från växterna. Cellodlingarnas egenskaper och syntetiserade ämnen kan analyseras och modifieras i laboratorier. I experimentella delen av detta arbete utvecklades ett system där man extraherade, fraktionerade och isolerade alkaloider från torkat cellmaterial av odlade R. stricta hairy root-celler. Målet var att utveckla ett fungerade system för att slutligen kunna identifiera vilka alkaloider de odlade cellerna syntetiserar under givna förhållanden. Alkaloider extraherades ur 26 g torkad och malen cellmassa. Fraktioneringen gjordes med hjälp av mediumtryck vätskekromatografi (eng. medium pressure liquid chromatography, MPLC) och fraktionerna analyserades med hjälp av tunnskiktskromatografi (eng. thin-layer chromatography, TLC) och högtrycksvätskekromatografi (eng. high-performance liquid chromatography, HPLC). Vid rengöringen av alkaloider användes horisontell TLC och preparativ HPLC. Jonparskromatografi användes vid analys av extraktet, fraktionerna och de rengjorda alkaloiderna. Slutligen isolerades sammanlagt fem komponenter ur två fraktioner. En av komponenterna, vincanin, identifierades preliminärt, men vidare analyser måste göras, för att med säkerhet identifiera alla komponenter. Allt som allt verkar hairy root-cellerna syntetisera några tiotal alkaloider med varierande polaritet.
  • Avellan, Eija (2005)
    Tutkielmassa tarkastellaan extranet-informaation hallintaa extranetiä käyttävissä tietointensiivisissä organisaatioissa. Työn tavoitteena on selvittää, a) miten organisaatioiden toimintakäytännöt selittävät sitä, missä laajuudessa extranet on otettu niissä käyttöön b) mikä on extranetin ja siinä olevan informaation merkitys käyttäjille sekä c) mihin extranetin informaatiota käytetään ja miten sitä jaetaan organisaatioissa. Tutkielmassa extranetillä tarkoitetaan sidosryhmille suunnatun informaation yksisuuntaiseen välittämiseen käytettävää järjestelmää, jossa ei ole operatiivisia toimintoja. Tutkimusongelma liittyy tilanteeseen, jossa extranet on ollut yleisesti organisaatioiden käytössä 1990-luvulta asti, mutta aihetta koskevaa kirjallisuutta ja tutkimusta on toistaiseksi olemassa melko vähän. Tutkielman teoreettinen viitekehys kattaa tietojohtamisen (knowledge management) kirjallisuutta. Tärkeimmät teoriat ovat Choon informaation hallinnan prosessimalli, Hansenin et al. tietojohtamisen strategiat sekä Taylorin informaation käyttöluokat. Viitekehyksen tärkein merkitys tutkielmalle on toimia työkaluna, jota vasten empiiristä aineistoa peilataan, lisäksi viitekehys toimii aineiston käsitteellistämisen apuna. Tutkielma on luonteeltaan laadullinen tapaustutkimus. Empiirinen aineisto koostuu edunvalvontayhdistyksen, Lääketeollisuus ry:n, neljän jäsenyrityksen teemahaastatteluista. Haastateltavat edustavat organisaatioiden asiantuntijatasoa sekä ylintä johtoa. Aineiston analyysimenetelmänä käytetään teemoittelua. Tutkielmassa todetaan, että extranetin käyttöoikeuksien laajuutta organisaatioissa selittävät toiminnan organisointi, johdon optimismi ja työntekijöiden toimenkuvat. Extranetin merkitys on käyttäjille melko laaja, ja käyttäjät painottavat esimerkiksi ajankohtaisuutta, luotettavuutta, tulkintojen merkitystä sekä käytön reaktiivisuutta. Extranet-informaatiota käytetään organisaatioissa toimintaympäristön luotauksessa, ongelmanratkaisu- ja päätöksentekoprosesseissa sekä toiminnan suunnittelussa. Extranet-informaation jakaminen on epävirallista, käytännöt vaihtelevia eikä organisaatioissa ole määritelty informaation jakamisen suhteen vastuita. Hansenin et al. tietojohtamisen strategioista organisaatioissa näyttää vallitsevan erityisesti personointistrategia. Tutkielmassa havaitaan, että tietojohtamisessa ja informaation hallinnassa keskiössä ovat niin organisaation johto, yksilöt kuin teknologiakin. Johto voi omalla toiminnallaan luoda puitteet organisaation toimintakäytäntöihin, mutta myös yksilöiden näkemyksillä on merkitystä siinä, miten informaatiota jaetaan ja kenen koetaan olevan vastuussa tiedon kehittämisestä. Tutkittavissa organisaatioissa havaitaan kahden ääripään näkemyksiä: toisen ääripään mukaan extranet-informaatiota ei tarvitse erityisesti jakaa, toisen ääripään mukaan jakaminen on koko organisaation eduksi. Johdolla ei aina ole käsitystä organisaation toimintakäytännöistä, eikä se siten kyseenalaista näitä käytäntöjä. Tärkeimpiä lähteitä tutkielmassa ovat: Hansen et al. (1999): What"s your strategy for managing knowledge?; Choo, Chun Wei (1998): The knowing organization; Choo, Chun Wei (2000): Information management for the intelligent organization; Taylor, Robert (1991): Information Use Environments.
  • Oravisto, Liisa (Helsingfors universitet, 2014)
    The European Court of Human Rights has brought a revolutionary aspect to the extraterritorial application of its Convention by extending it to cover the state parties’ actions abroad. By opening the door to the application of the European Convention on Human Rights to activities of a member state beyond its territorial borders, the Court has changed its case-law practice from more restrictive to more allowing. The major authority on the extraterritorial application of the ECHR has thus far been the Bankovi? v Belgium case from 2001. In Bankovi? the Court decided on the claims against 17 NATO states for the bombardments in Yugoslavia in 1999. The Court dismissed the claims on the basis of jurisdiction as it held that the jurisdictional threshold of Article 1 of the ECHR was not met. Contrary to Bankovi?, the Court decided on Al-Skeini and Al-Jedda positively on the application of the Convention outside of its direct territory. This is a big change in the practice and will have an even bigger impact on the states and thus it is now time to reevaluate the issue in light of these new cases. The incoherence of the Court’s judgments places the states, and individuals, in an unpredictable world as the meaning of ‘within their jurisdiction’ as set out in Article 1 of the Convention remains controversial. The two identities of the Convention as a regional, European instrument and as a universal human rights mechanism create a challenging relationship. This thesis explores the change in the Court’s interpretation views through the case law concerning the extraterritorial application of the ECHR. For a global comparison other human rights treaties and their jurisdiction clauses are reviewed in order to evaluate the status quo in this field and the impacts on states’ actions and respective policies thereof. The Article 1 plays a fundamental role in this context and thus it is reflected throughout the thesis.
  • Grönholm, Jessica (University of Helsinki, 2015)
    This thesis addresses the role of home states in relation to extraterritorial human rights violations committed by their corporate nationals, more specifically transnational corporations (TNCs). This thesis examines the difficulties of holding TNCs directly accountable for the violations they commit. Secondly, this thesis explores whether and to what extent home states of TNCs can become responsible for extraterritorial human rights violations committed by TNCs domiciled in their territories. This thesis approaches the issue of home state responsibility from two separate points of view namely the law on state responsibility and international human rights law. Growing corporate power and its possible detrimental impact on the enjoyment of human rights has not gone unnoticed. TNCs’ corporate structures are as the name says, transnational, and their operations are commonly global. This in turn leads to a situation in which the operations of a TNC existing under the laws of one state may impact the lives of people located in other the countries hosting the operations of the TNC. Although some attempts have been made in the international legal sphere to keep corporations directly accountable for the human rights violations they commit, under the current state of international law, no legally binding provisions exist to keep corporations directly accountable. Focus has therefore been on states’ obligations to ensure the adequate protection of human rights and this thesis stresses the obligations of the home state. The two separate approaches to state responsibility examined in this thesis are built on very different premises. Firstly, the law of state responsibility provides the circumstances pursuant to which the acts of TNCs can become attributable to the home state as an act of state. As a general rule, private acts are not automatically imputable to the state, but may under certain circumstances be considered as such. This thesis explores the exemptions to this basic rule of non-attribution and the conditions when a state can be held responsible for the acts of TNCs. Pursuant to the rules of state responsibility, acts of TNCs may become attributable to the home state in four situations, namely when the TNC has the status of an organ of the state de facto or de jure; when the TNC has been authorized to exercise governmental authority; when the TNC has acted under the instructions, direction or control of the state and when the home state acknowledges and adopts the conduct as its own. However, as this thesis demonstrates the criteria for attribution of TNCs’ conduct to the state are rather strict and the practical usefulness of the law of state responsibility for the purposes of keeping home states responsible for human rights abuse is rather speculative. The second approach adopted in this thesis finds its basis in human rights law. It is widely acknowledged that states are under an obligation to respect, protect and fulfil human rights. Of these three aspects, the obligation to protect is central to this thesis as it concerns the state’s duty to protect human rights of individuals from infringements of non-state actors such as TNCs. The positive duties to protect human rights have traditionally been perceived to apply in the domestic territories of the state, and this thesis examines whether the home states of a TNC can be under an obligation to extend this protection to the human rights of people in third states and thus to control their corporate nationals by means of e.g. legislation. The recent developments in this field signal of a willingness to recognize and strengthen the duties of home states’ extraterritorial obligations. This is perhaps due to the fact that recent initiatives have on the one hand abandoned the idea of direct corporate accountability and relied solely on the permissibility of home state regulation, which is insufficient and gives rise to governance gaps. However, the work of various human rights treaty bodies signal of the possibility of recognizing such home state obligations and is also discussed in this thesis. Conclusively, the discussion in this thesis provides that home states can incur state responsibility under certain rather strict conditions. The conclusions also highlight that of the two approaches addressed in this thesis, international human rights law is perhaps a better tool in this regard. Nevertheless, the existence of legally binding norms is still an unresolved matter. Therefore the conclusions of this thesis observe the need to clarify the precise scope of the extraterritorial obligations of home states with regard to control of TNCs.