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  • Johansson, Maria (2013)
    Dispersive liquid-liquid microextraction was developed in 2006 for the extraction of organic compounds from water samples. Since then, more complex matrices have been processed and the technique includes nowadays a variety of subsets. To the advantages of the technique are, for example, its rapidity, low cost and high enrichment factors. A pretreatment and analysis method was developed for the five harmful flame retardants, dechlorane plus (syn and anti) and dechloranes 602, -603 and -604 (component A) from solid environmental samples. The pretreatment method included extraction with pressurised liquid extraction and clean-up with multilayer silica and basic alumina columns. The analytes were separated and analysed with gas chromatography coupled to mass spectrometry. Electron capture negative ionisation was applied as the ionisation technique. The developed method was sensitive, resulting in acceptable recoveries and low detection limits. The chosen ionisation technique was proven to be superior over the more used electron ionisation.
  • Wayessa, Gutu Olana (Helsingin yliopisto, 2013)
    The study focuses on population displacement and the livelihood implications of state-planned resettlement schemes that have been implemented in Western Oromia, Ethiopia. It addresses the livelihoods of both the resettlers and the hosts. Although such resettlements have been implemented in the country since the 1960s, this study addresses those carried out since 2003. The broad objective of the study was to explore the dynamics of displacement and resettlement, and their impacts on the livelihoods of resettler and host populations. The specific objectives were: (1) to assess the policies and practices of the resettlement program carried out during the tenure of the current government; (2) to analyze the livelihood outcomes of the resettlements for resettlers and hosts in terms of changes in access to livelihood resources and social services; and (3) to examine resettlers and hosts perceptions of and attitudes towards the resettlement program. The theory of impoverishment risks and livelihood reconstruction (IRLR), the sustainable livelihood framework (SLF), and political ecology constitute the pillars of the theoretical framework. Primary data were collected in 2009 through a survey of 630 households in eight resettlement sites, and 68 thematic (group and individual) interviews in 13 resettlement sites. Several interviews were also held with government officials. Households were selected for the survey through stratified random sampling, whereas informants were selected for the interviews purposively. The primary data were complemented with relevant secondary data. The study is interdisciplinary, and combines both qualitative and quantitative methods through a concurrent mixed-methods design. Qualitative methods were used to address how and why questions through thematic analysis of the interviews and policy documents, thereby illuminating the substantive significance of the issues at stake. Quantitative methods were employed to quantify changes and establish the statistical significance of variables of interest. The quantitative methods used include descriptive statistics, such as percentages, means and cross-tabulations, and inferential statistics, such as logistic regression, mean comparisons using non-parametric tests, factor analysis, Chi-square tests, and loglinear analysis. The complementary relation between the two methods has proved useful in understanding and explaining the processes and the outcomes of the resettlement scheme. The research illuminates the causes, the processes, and the outcomes of the current resettlement program in particular, and critically analyzes the assumptions underlying the resettlement policies of the current and the previous regimes in general. Multiple causes and assumptions underlay the resettlement scheme, most notably land and rainfall shortages in resettlers areas of origin, and the government s claim of land abundance. This last assumption has been persistently made by regime after regime, despite empirical counter-evidence, as also shown in this study. By revealing that the scheme resulted in the displacement of the host population to make way for resettlement, that the resettlers were given less land than promised, and that the relocation led to serious conflicts and disputes over land between resettlers and hosts, the study challenges the state s supposition and rhetoric of ample land. The evidence also illuminates the relocation s glaring lack of inclusiveness of both resettlers and hosts, despite the benign principles of voluntarism and consultation. The outcomes were multiple, leaving some better-off, others worse-off, and still others with no noticeable livelihood deterioration or improvement. In cases where old problems were alleviated, new ones emerged in a context of little plan and capacity to meet contingencies. This calls into question government propagation of generalized success in the resettlement scheme. Although little is known about the sustainability of the improved outcomes for some resettlers in some resettlement sites, the evidence from this study also counteracts the depiction of the scheme as a general failure. The findings suggest that the relative importance of the risks experienced by the resettlers and the hosts varied between the two population groups, and among different resettlement sites. The resettlement sites were widely differentiated in terms of biophysical factors, notably soil fertility and the availability of grazing land. This has serious implications for the resettlers and the hosts as their livelihoods are almost entirely based on agricultural activities. Moreover, historical issues, wider socio-political structures, physical infrastructure, and resettler-host relations are crucial for the understanding of how people s access to livelihood resources and social services is shaped. However, resettler-host relations should be seen in a broader context of state-society relations, as the state is a key actor in planning and implementing the resettlement programs. An important policy lesson from this study is that when one focuses on certain livelihood aspects, one also needs to be aware that other potential livelihood components not evident today may become vital in the future. This awareness should motivate adaptive planning and management to meet contingencies in a way that reflects the multifaceted nature of livelihoods. Key words: displacement, resettlement, livelihood, resettler, host, state, IRLR, SLF, political ecology, mixed methods, resources, processes, outcomes, Oromia, Ethiopia
  • Ylikoski, Petri (Helsingin yliopisto, 1997)
  • Puurunen, Tapio (Helsingin yliopisto, 2005)
  • Kousi, Maria (Helsingin yliopisto, 2012)
    The progressive myoclonic epilepsies (PMEs) are a clinically and etiologically heterogeneous group of symptomatic epilepsies characterized by myoclonus, tonic-clonic seizures, psychomotor regression and ataxia. Different disorders have been classified as PMEs. Of these, the group of neuronal ceroid lipofuscinoses (NCLs) comprise an entity that has onset in childhood, being the most common cause of neurodegeneration in children. The primary aim of this thesis was to dissect the molecular genetic background of patients with childhood onset PME by studying candidate genes and attempting to identify novel PME-associated genes. Another specific aim was to study the primary protein properties of the most recently identified member of the NCL-causing proteins, MFSD8. To dissect the genetic background of a cohort of Turkish patients with childhood onset PME, a screen of the NCL-associated genes PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8 and CTSD was performed. Altogether 49 novel mutations were identified, which together with 56 mutations found by collaborators raised the total number of known NCL mutations to 364. Fourteen of the novel mutations affect the recently identified MFSD8 gene, which had originally been identified in a subset of mainly Turkish patients as the underlying cause of CLN7 disease. To investigate the distribution of MFSD8 defects, a total of 211 patients of different ethnic origins were evaluated for mutations in the gene. Altogether 45 patients from nine different countries were provided with a CLN7 molecular diagnosis, denoting the wide geographical occurrence of MFSD8 defects. The mutations are private with only one having been established by a founder-effect in the Roma population from the former Czechoslovakia. All mutations identified except one are associated with the typical clinical picture of variant late-infantile NCL. To address the trafficking properties of MFSD8, lysosomal targeting of the protein was confirmed in both neuronal and non-neuronal cells. The major determinant for this lysosomal sorting was identified to be an N-terminal dileucine based signal (9-EQEPLL-14), recognized by heterotetrameric AP-1 adaptor proteins, suggesting that MFSD8 takes the direct trafficking pathway en route to the lysosomes. Expression studies revealed the neurons as the primary cell-type and the hippocampus and cerebellar granular cell layer as the predominant regions in which MFSD8 is expressed. To identify novel genes associated with childhood onset PME, a single nucleotide polymorphism (SNP) genomewide scan was performed in three small families and 18 sporadic patients followed by homozygosity mapping to determine the candidate loci. One of the families and a sporadic patient were positive for mutations in PLA2G6, a gene that had previously been shown to cause infantile neuroaxonal dystrophy. Application of next-generation sequencing of candidate regions in the remaining two families led to identification of a homozygous missense mutation in USP19 for the first and TXNDC6 for the second family. Analysis of the 18 sporadic cases mapped the best candidate interval in a 1.5 Mb region on chromosome 7q21. Screening of the positional candidate KCTD7 revealed six mutations in seven unrelated families. All patients with mutations in KCTD7 were reported to have early onset PME, rapid disease progression leading to dementia and no pathologic hallmarks. The identification of KCTD7 mutations in nine patients and the clinical delineation of their phenotype establish KCTD7 as a gene for early onset PME. The findings presented in this thesis denote MFSD8 and KCTD7 as genes commonly associated with childhood onset symptomatic epilepsy. The disease-associated role of TXNDC6 awaits verification through identification of additional mutations in patients with similar phenotypes. Completion of the genetic spectrum underlying childhood onset PMEs and understanding of the gene products functions will comprise important steps towards understanding the underlying pathogenetic mechanisms, and will possibly shed light on the general processes of neurodegeneration and nervous system regulation, facilitating the diagnosis, classification and possibly treatment of the affected cases.
  • Müller, Susann (Helsingin yliopisto, 2015)
    Biogeochemical processes in sea ice and the ice-water interface depend on abiotic processes and biological activity. Abiotic processes in sea ice are controlled by the crystallization process of freezing water and the associated formation of saline brine. Also the heat budget of sea ice and the resulting changes in abiotic properties such as porosity and salinity need to be taken into account. The dissolved fraction of sea ice brines contain ions and dissolved organic matter (DOM). Ions are rejected from the ice by diffusion and gravity drainage whereas dissolved organic matter with highly complex and diverse chemical composition can react in many ways with other molecules and surfaces. Hence, the present work compares the behavior of different fractions of DOM to the ones of salts during initial sea ice formation. Controlled tank studies were combined with natural sea ice sampling to exclude the disadvantages of both systems such as the effects of small-scale experiments, artificial additions in tank experiments and the unknown history of natural samples. The studies were conducted with brackish sea ice from the Baltic Sea with its high nutrient and DOM concentrations, but also with oceanic sea ice from the North Sea and the Arctic Ocean. This allows a general conclusion about the behavior of solutes during the formation of sea ice. The present studies indicate that the major seawater ions are significantly fractionated due to differential diffusion and coupled diffuse-convective salt transport through the brine channel network. Ions with a lower diffusivity than Cl¯, in this study SO42¯, Ca+ and Mg2+, remained longer in the brine channel network and got therefore enriched in sea ice relative to Cl¯. K+, on the other hand, diffused faster than Cl¯ and was depleted in sea ice in this study. The behavior of DOM in sea ice was more complex compared to ions because of the complex structure of DOM and the effect of secondary processes on DOM, such as biological production and degradation in sea ice. The quantification of DOM is challenging since only certain fractions such as chromophoric DOM can be measured instead of estimating the total concentration of DOM. Nevertheless, the present studies on DOM in sea ice from Baltic and North Sea water indicated enrichment of DOM compared to sea water ions. The magnitude of this enrichment was higher than expected from diffusion and convection following the transport of salts. The enrichment varied among DOM fractions with highest enrichment of amino-acid like DOM and lowest enrichment of humic-like substances. The results therefore suggest that additional processes, such as selective drainage that depends on the chemical properties of the DOM molecules, affect the enrichment of DOM in sea ice. The optical properties of sea ice were used to develop a bio-optical model. The model estimates the primary production in Baltic Sea ice based on the absorption by particles and chromophoric DOM and the quantum yield for C fixation calculated from photosynthesis-irradiance curves. The results were compared to in situ primary production measurements. The combination of modelled primary production estimates and the measurements of optical properties and primary production in different types of Baltic Sea ice gave a good overview over bio-optical properties in Baltic Sea ice and can be used as a tool to improve different parameters of ecosystem models.
  • Lehecka, Martin (Helsingin yliopisto, 2009)
    Objective: Distal anterior cerebral artery (DACA) aneurysms represent about 6% of all intracranial aneurysms. So far, only small series on treatment of these aneurysms have been published. Our aim is to evaluate the anatomic features, microneurosurgical techniques, treatment results, and long-term outcome in patients treated for DACA aneurysms. Patients and methods: We analyzed the clinical and radiological data on 517 consecutive patients diagnosed with DACA aneurysm at two neurosurgical centers serving solely the Southern (Helsinki) and Eastern (Kuopio) Finland in 1936–2007, and used a defined subgroup of the whole study population in each part of the study. Detailed anatomic analysis was performed in 101 consecutive patients from 1998 to 2007. Treatment results were analyzed in 427 patients treated between 1980 to 2005, the era of CT imaging and microneurosurgery. Long-term treatment outcome of ruptured DACA aneurysm(s) was evaluated in 280 patients with a median follow-up of 10 years; no patients were lost to follow-up. Results: DACA aneurysms, found most often (83%) at the A3 segment of the anterior cerebral artery (ACA), were smaller (median 6 mm vs. 8 mm), more frequently associated with multiple aneurysms (35% vs. 18%), and presented more often with intracerebral hematomas (ICHs) (53% vs. 26%) than ruptured aneurysms in general. They were associated with anomalies of the ACA in 23% of the patients. Microsurgical treatment showed similar complication rates (treatment morbidity 15%, treatment mortality 0.4%) as for other ruptured aneurysms. At one year after subarachnoid hemorrhage (SAH), DACA aneurysms had equally favorable outcome (GOS≥4) as other ruptured aneurysms (74% vs. 69%) but their mortality was lower (13% vs. 24%). Factors predicting unfavorable outcome for ruptured DACA aneurysms were advanced age, Hunt&Hess≥3, rebleeding before treatment, ICH, intraventricular hemorrhage, and severe preoperative hydrocephalus. The cumulative relative survival ratio showed 16% excess mortality in patients with ruptured DACA aneurysm during the first three years after SAH compared to the matched general population. From the fourth year onwards, there was no excess mortality during the follow-up. There were four episodes of recurrent SAH, only one due to treated DACA aneurysm, with a 10-year cumulative risk of 1.4%. Conclusions: The special neurovascular features and frequent association with anterior cerebral artery anomalies must be taken into account when planning occlusive treatment of DACA aneurysms. Clipping of DACA aneurysms provides a long-lasting result, with very small rates of rebleeding. After surviving three years from rupture of DACA aneurysm, the long-term survival of these patients becomes similar to that of the matched general population.
  • Kärkkäinen, Simo (2015)
    Tutkimus keskittyy suomalaisen 1970-luvun rocklehdistön historiaan ja asemaan kotimaisella musiikin kentällä. Musan ja Soundin kirjoituksia on tarkasteltu hyödyntäen Pierre Bourdieun distinktioteoriaa. Tutkielmassa on tarkasteltu aineistossa esiintyviä bourdieulaisia kulttuurikentän erityispiirteitä, distinktion eli erottumisen tapoja sekä kentän sisällä syntyneitä konflikteja. Tutkimusongelmaa on lähestytty seuraavan tutkimuskysymyksen avulla: Millaisia bourdieulaisia distinktioita ja kenttäkonflikteja suomalaisessa 1970-luvun rocklehdistössä ilmenee? Lisäksi on pohdittu, mitä rocklehtien distinktiot ja konfliktit kertovat ympäröivästä yhteiskunnasta ja miten musiikin kenttä mahdollisesti muuttui 1970-luvun kuluessa. Aineisto koostuu Musa- ja Soundi -lehtien vuosikerroista. Ensimmäinen Musa julkaistiin vuonna 1972 ja ensimmäinen Soundi vuonna 1975. Kyseessä ovat ainoat laajalevikkiset suomalaiset rocklehdet tutkitulta ajalta. Musan säännöllinen julkaiseminen alkoi vuoden 1972 heinäkuussa ja loppui 1978. Soundi julkaistiin ensimmäisen kerran vuonna 1975, ja lehti ilmestyy edelleen. Analyysi on rakentunut temaattisesti suuremmasta kokonaisuudesta pienempään siten, että aluksi on käsitelty Suomen rocklehdistön identifioitumista laajalla musiikin kentällä, minkä jälkeen tarkastellaan rocklehtien toimintaa suomalaisella kulttuurin kentällä. Lopuksi käydään läpi Musan ja Soundin välistä konfliktia. Rocklehtien tärkein distinktiomuoto läpi 1970-luvun oli kiistatta autenttisuus. Autenttisuuden muodot olivat Suomessa jokseenkin moninaisia, mutta ne kiteytyvät viime kädessä yleensä epäkaupallisuuteen sekä romanttiseen ihanteeseen itsenäisestä ja vilpittömästä taiteilijasta. Autenttisuuden ihannointimuodot rockin kentällä sekä niihin perustuvat distinktiot syntyivät angloamerikkalaisessa rockkulttuurissa, ja ne periytyivät suomalaiseen rockkirjoitteluun lähes sellaisinaan. Autenttisuutta ihannoimalla rocklehdet erottuivat suomalaisesta vallitsevasta musiikkikentän eliitistä, nuortenlehdistä, toisistaan sekä paikoin ylikaupalliseksi kokemastaan musiikkiteollisuudesta. Konfliktit syntyivät, kun rocklehdet pyrkivät kasvattamaan symbolista pääomaansa ja kyseenalaistamaan kentän eliittiä ja kilpailijoitaan. Konfliktienkin ytimessä oli usein autenttisuuden ihannointi sekä käsityserot autenttisuuden merkityksestä. Rocklehdet ottivat myös näkyvästi kantaa suomalaiseen musiikkipolitiikkaan. Keskeistä rocklehtien kulttuuripoliittiselle kirjoittelulle on pyrkimys muodostaa sukupolvikonflikti, jossa vakiintuneen kentän paradigmaa kyseenalaistetaan oman aseman edesauttamiseksi. Rocklehdet halusivat horjuttaa suomalaisen kulttuurieliitin vakiintunutta asemaa voidakseen itse määritellä legitiimin taiteen ja kulttuurituotteiden ehdot. Lisäksi Musa ja Soundi tekivät distinktioita toisiinsa ja yrittivät saavuttaa valta-asemaa omalla kentällään. Lehtien autenttisuuteen ja epäkaupallisuuteen pyrkiminen heijastelee näkyvästi 1970-lukulaista yhteiskuntaa, joka oli toisaalta hidastuneen talouskasvun leimaama ja jonka musiikkikenttä kuitenkin kaupallistui nopeasti suurten levy-yhtiöiden kasvaessa ja vahvistaessa markkinaosuuttaan. Yhteiskunnan ja populaarimusiikin kehitys koettiin rocklehdissä pitkälti rappiollisena, ja tilanteen pelastajana nähtiin autenttisuuden vaaliminen ja oletetun rahakeskeisyyden hylkääminen.
  • Prause, Istvan (Helsingin yliopisto, 2007)
    Quasiconformal mappings are natural generalizations of conformal mappings. They are homeomorphisms with 'bounded distortion' of which there exist several approaches. In this work we study dimension distortion properties of quasiconformal mappings both in the plane and in higher dimensional Euclidean setting. The thesis consists of a summary and three research articles. A basic property of quasiconformal mappings is the local Hölder continuity. It has long been conjectured that this regularity holds at the Sobolev level (Gehring's higher integrabilty conjecture). Optimal regularity would also provide sharp bounds for the distortion of Hausdorff dimension. The higher integrability conjecture was solved in the plane by Astala in 1994 and it is still open in higher dimensions. Thus in the plane we have a precise description how Hausdorff dimension changes under quasiconformal deformations for general sets. The first two articles contribute to two remaining issues in the planar theory. The first one concerns distortion of more special sets, for rectifiable sets we expect improved bounds to hold. The second issue consists of understanding distortion of dimension on a finer level, namely on the level of Hausdorff measures. In the third article we study flatness properties of quasiconformal images of spheres in a quantitative way. These also lead to nontrivial bounds for their Hausdorff dimension even in the n-dimensional case.
  • Hirvonen, Juho (2012)
    In this work we study a graph problem called edge packing in a distributed setting. An edge packing p is a function that associates a packing weight p(e) with each edge e of a graph such that the sum of the weights of the edges incident to each node is at most one. The task is to maximise the total weight of p over all edges. We are interested in approximating a maximum edge packing and in finding maximal edge packings, that is, edge packings such that the weight of no edge can be increased. We use the model of distributed computing known as the LOCAL model. A communication network is modelled as a graph, where nodes correspond to computers and edges correspond to direct communication links. All nodes start at the same time and they run the same algorithm. Computation proceeds in synchronous communication rounds, during each of which each node can send a message through each of its communication links, receive a message from each of its communication links, and then do unbounded local computation. When a node terminates the algorithm, it must produce a local output – in this case a packing weight for each incident edge. The local outputs of the nodes must together form a feasible global solution. The running time of an algorithm is the number of steps it takes until all nodes have terminated and announced their outputs. In a typical distributed algorithm, the running time of an algorithm is a function of n, the size of the communication graph, and Δ, the maximum degree of the communication graph. In this work we are interested in deterministic algorithms that have a running time that is a function of Δ, but not of n. In this work we will review an O(log Δ)-time constant-approximation algorithm for maximum edge packing, and an O(Δ)-time algorithm for maximal edge packing. Maximal edge packing is an example of a problem where the best known algorithm has a running time that is linear-in-Δ. Other such problems include maximal matching and (Δ+1)-colouring. However, few matching lower bounds exist for these problems: by prior work it is known that finding a maximal edge packing requires time Ω(log Δ), leaving an exponential gap between the best known lower and upper bounds. Recently Hirvonen and Suomela (PODC 2012) showed a linear-in-Δ lower bound for maximal matching. This lower bound, however, applies only in weaker, anonymous models of computation. In this work we show a linear-in-Δ lower bound for maximal edge packing. It applies also in the stronger port numbering model with orientation. Recently Göös et al. (PODC 2012) showed that for a large class of optimisation problems, the port numbering with orientation model is as powerful as a stronger, so called unique identifier model. An open question is if this result can applied to extend our lower bound to the unique identifier model.
  • Mäki, Jussi Olavi Aleksis (2013)
    With the increasing growth of data traffic in mobile networks there is an ever growing demand from the operators for a more scalable and cost efficient network core. Recent successes in deploying Software-Defined Networking (SDN) in data centers and large network backbones has given it credibility as a viable solution for meeting the requirements of even the large core networks. Software-Defined Networking is a novel new paradigm where the control logic of the network is separated from the network elements into logically centralized controllers. This separation of concerns offers more flexibility in network control and makes writing of new management applications, such as routing protocols, easier, faster and more manageable. This thesis is an empirical experiment in designing and implementing a scalable and fault- tolerant distributed SDN controller and management application for managing the GPRS Tunneling Protocol flows that carry the user data traffic within the Evolved Packet Core. The experimental implementation is built using modern open-source distributed system tools such as the Apache Zookeeper distributed coordination service and Basho’s Riak distributed key-value database. In addition to the design, a prototype implementation is presented and its performance is evaluated.
  • Vainionpää, Noora (nyk. Noora Skants) (Helsingin yliopisto, 2008)
    Basement membranes are specialized sheets of extracellular matrix found in contact with epithelia, endothelia, and certain isolated cells. They support tissue architecture and regulate cell behaviour. Laminins are among the main constituents of basement membranes. Due to differences between laminin isoforms, laminins confer structural and functional diversity to basement membranes. The first aim of this study was to gain insights into the potential functions of the then least characterized laminins, alpha4 chain laminins, by evaluating their distribution in human tissues. We thus created a monoclonal antibody specific for laminin alpha4 chain. By immunohistochemistry, alpha4 chain laminins were primarily localized to basement membranes of blood vessel endothelia, skeletal, heart, and smooth muscle cells, nerves, and adipocytes. In addition, alpha4 chain laminins were found in the region of certain epithelial basement membranes in the epidermis, salivary gland, pancreas, esophagus, stomach, intestine, and kidney. Because of the consistent presence of alpha4 chain laminins in endothelial basement membranes of blood vessels, we evaluated the potential roles of endothelial laminins in blood vessels, lymphatic vessels, and carcinomas. Human endothelial cells produced alpha4 and alpha5 chain laminins. In quantitative and morphological adhesion assays, human endothelial cells barely adhered to alpha4 chain-containing laminin-411. The weak interaction of endothelial cells with laminin-411 appeared to be mediated by alpha6beta1 integrin. The alpha5 chain-containing laminin-511 promoted endothelial cell adhesion better than laminin-411, but it did not promote the formation of cell-extracellular matrix adhesion complexes. The adhesion of endothelial cells to laminin-511 appeared to be mediated by Lutheran glycoprotein together with beta1 and alphavbeta3 integrins. The results suggest that these laminins may induce a migratory phenotype in endothelial cells. In lymphatic capillaries, endothelial basement membranes showed immunoreactivity for laminin alpha4, beta1, beta2, and gamma1 chains, type IV and XVIII collagens, and nidogen-1. Considering the assumed inability of alpha4 chain laminins to polymerize and to promote basement membrane assembly, the findings may in part explain the incomplete basement membrane formation in these vessels. Lymphatic capillaries of ovarian carcinomas showed immunoreactivity also for laminin alpha5 chain and its receptor Lutheran glycoprotein, emphasizing a difference between normal and ovarian carcinoma lymphatic capillaries. In renal cell carcinomas, immunoreactivity for laminin alpha4 chain was found in stroma and basement membranes of blood vessels. In most tumours, immunoreactivity for laminin alpha4 chain was also observed in the basement membrane region of tumour cell islets. Renal carcinoma cells produced alpha4 chain laminins. Laminin-411 did not promote adhesion of renal carcinoma cells, but inhibited their adhesion to fibronectin. Renal carcinoma cells migrated more on laminin-411 than on fibronectin. The results suggest that alpha4 chain laminins have a counteradhesive function, and may thus have a role in detachment and invasion of renal carcinoma cells.
  • Nurmi, Satu (2015)
    Many drugs are known to bind to melanin, a complex pigment polymer found in several human tissues. Melanin can act as a natural depot by prolonging the effect of the drug and reducing its toxicity. Since it is highly concentrated in the posterior part of the eye, pigment targeted long-acting drug delivery systems are proposed as an option in ocular diseases. In systemic drug delivery, pigment targeted drugs can potentially distribute to any melanin containing tissue. Therefore, the literature review of the thesis concentrates on the characteristics of melanin and melanosomes, drug binding property and melanin distribution in humans and other species. The main objective of the exploratory part was to determine if melanin binding can be studied with SPECT/CT (single photon emission computed tomography / computed tomography) imaging method. Two different melanin binding drugs, chloroquine and nadolol, were selected and labeled with iodine and radioactive iodine (123I). Equilibrium melanin binding of iodinated and non-iodinated drugs was studied in vitro in order to find out if iodination affects to the binding. Melanin binding was studied in vitro also with non-binding reference salicylic acid, I2-salicylic acid and salbutamol. Finally, melanin binding of 123I-choloroquine and 123I-nadolol was studied with SPECT/CT (NanoSPECT/CT, Bioscan Inc., USA) by comparing distribution kinetics between pigmented and albino rat. Drugs were administered intravenously to the tail vena and the distribution was followed in several time points, up to 24 h. Based on in vitro study, iodination increases melanin binding of hydrophilic drugs, nadolol and salicylic acid, significantly. In vivo study showed clear accumulation of 123I-chloroquine in the posterior eye of pigmented rats whereas it was absent from albino rat. Interestingly, 123I-nadolol accumulated in to the nasal cavity of pigmented rats. Aromatic iodination changes electronegative properties of compounds and raises their logP (octanol/water partition coefficient) value affecting to the melanin binding positively. Therefore the effect of the radiotracer to the physicochemical properties of the compound and melanin binding should be determined in vitro. This study showed that SPECT/CT imaging method can be used to study melanin binding in vivo. Because the method is semi-quantitative, also a quantitative method should be incorporated to the study in order to have more powerful data. Additional studies are required for statistical analysis.
  • Nurmi, Satu (2014)
    Many drugs are known to bind to melanin, a complex pigment polymer found in several human tissues. Melanin can act as a natural depot by prolonging the effect of the drug and reducing its toxicity. Since it is highly concentrated in the posterior part of the eye, pigment targeted long-acting drug delivery systems are proposed as an option in ocular diseases. In systemic drug delivery, pigment targeted drugs can potentially distribute to any melanin containing tissue. Therefore, the literature review of the thesis concentrates on the characteristics of melanin and melanosomes, drug binding property and melanin distribution in humans and other species. The main objective of the exploratory part was to determine if melanin binding can be studied with SPECT/CT (single photon emission computed tomography / computed tomography) imaging method. Two different melanin binding drugs, chloroquine and nadolol, were selected and labeled with iodine and radioactive iodine (123I). Equilibrium melanin binding of iodinated and non-iodinated drugs was studied in vitro in order to find out if iodination affects to the binding. Melanin binding was studied in vitro also with non-binding reference salicylic acid, I2-salicylic acid and salbutamol. Finally, melanin binding of 123I-choloroquine and 123I-nadolol was studied with SPECT/CT (NanoSPECT/CT, Bioscan Inc., USA) by comparing distribution kinetics between pigmented and albino rat. Drugs were administered intravenously to the tail vena and the distribution was followed in several time points, up to 24 h. Based on in vitro study, iodination increases melanin binding of hydrophilic drugs, nadolol and salicylic acid, significantly. In vivo study showed clear accumulation of 123I-chloroquine in the posterior eye of pigmented rats whereas it was absent from albino rat. Interestingly, 123I-nadolol accumulated in to the nasal cavity of pigmented rats. Aromatic iodination changes electronegative properties of compounds and raises their logP (octanol/water partition coefficient) value affecting to the melanin binding positively. Therefore the effect of the radiotracer to the physicochemical properties of the compound and melanin binding should be determined in vitro. This study showed that SPECT/CT imaging method can be used to study melanin binding in vivo. Because the method is semi-quantitative, also a quantitative method should be incorporated to the study in order to have more powerful data. Additional studies are required for statistical analysis.
  • Nyman, Marjut (Helsingin yliopisto, 2007)
    Climate change contributes directly or indirectly to changes in species distributions, and there is very high confidence that recent climate warming is already affecting ecosystems. The Arctic has already experienced the greatest regional warming in recent decades, and the trend is continuing. However, studies on the northern ecosystems are scarce compared to more southerly regions. Better understanding of the past and present environmental change is needed to be able to forecast the future. Multivariate methods were used to explore the distributional patterns of chironomids in 50 shallow (≤ 10m) lakes in relation to 24 variables determined in northern Fennoscandia at the ecotonal area from the boreal forest in the south to the orohemiarctic zone in the north. Highest taxon richness was noted at middle elevations around 400 m a.s.l. Significantly lower values were observed from cold lakes situated in the tundra zone. Lake water alkalinity had the strongest positive correlation with the taxon richness. Many taxa had preference for lakes either on tundra area or forested area. The variation in the chironomid abundance data was best correlated with sediment organic content (LOI), lake water total organic carbon content, pH and air temperature, with LOI being the strongest variable. Three major lake groups were separated on the basis of their chironomid assemblages: (i) small and shallow organic-rich lakes, (ii) large and base-rich lakes, and (iii) cold and clear oligotrophic tundra lakes. Environmental variables best discriminating the lake groups were LOI, taxon richness, and Mg. When repeated, this kind of an approach could be useful and efficient in monitoring the effects of global change on species ranges. Many species of fast spreading insects, including chironomids, show a remarkable ability to track environmental changes. Based on this ability, past environmental conditions have been reconstructed using their chitinous remains in the lake sediment profiles. In order to study the Holocene environmental history of subarctic aquatic systems, and quantitatively reconstruct the past temperatures at or near the treeline, long sediment cores covering the last 10000 years (the Holocene) were collected from three lakes. Lower temperature values than expected based on the presence of pine in the catchment during the mid-Holocene were reconstructed from a lake with great water volume and depth. The lake provided thermal refuge for profundal, cold adapted taxa during the warm period. In a shallow lake, the decrease in the reconstructed temperatures during the late Holocene may reflect the indirect response of the midges to climate change through, e.g., pH change. The results from three lakes indicated that the response of chironomids to climate have been more or less indirect. However, concurrent shifts in assemblages of chironomids and vegetation in two lakes during the Holocene time period indicated that the midges together with the terrestrial vegetation had responded to the same ultimate cause, which most likely was the Holocene climate change. This was also supported by the similarity in the long-term trends in faunal succession for the chironomid assemblages in several lakes in the area. In northern Finnish Lapland the distribution of chironomids were significantly correlated with physical and limnological factors that are most likely to change as a result of future climate change. The indirect and individualistic response of aquatic systems, as reconstructed using the chironomid assemblages, to the climate change in the past suggests that in the future, the lake ecosystems in the north do not respond in one predictable way to the global climate change. Lakes in the north may respond to global climate change in various ways that are dependent on the initial characters of the catchment area and the lake.