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Chimeric antigen receptor (CAR) T cells are genetically modified usually autologous T cells expressing de novo designed CAR that binds a specific antigen on the surface of the cancer cells, inducing T cell receptor-independent activation and cytotoxic response against the targeted cancer cells. While CAR T cells have been shown to offer effective treatment in acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma, several resistance mechanisms can lead to CAR T cell exhaustion characterized by impaired functions and the expression of inhibitory receptors. The Finnish Red Cross Blood Service has developed novel CARs, differing in structure from the ones currently published. Since the evasion of CAR T cell exhaustion is considered one of the key objectives in the development of CAR T cell therapy, this Master’s thesis project aimed to create a working method to determine the exhaustion of CAR T cells in vitro after long-term repeated stimulation. In order to induce and measure exhaustion, CAR T cells were produced and activated ex vivo in the presence of IL-2 or IL-7/IL-15 cytokines, cultured long-term and repeatedly stimulated by exposure to target cells. CAR T cell cytotoxicity and expansion were determined and the expression of various inhibitory receptors was analyzed. The method enabled the comparison of the designed CAR T cell candidates and the positive control CD19-CD28ζ CAR T cells in long-term cytotoxic potency. In addition, it helped to reveal the surprising difference between IL-2 and IL-7/IL-15 cytokines and their impact on CAR T cell exhaustion. Although CAR T cells produced with IL-2 had poorer expansion during CAR T cell production than CAR T cells produced with IL-7/IL-15, they showed lower expression of exhaustion-related markers supported by better survival, proliferation and cytotoxic activity during long-term repeated stimulation assay.

Metsätalouden seurauksena lahopuu on vähentynyt Suomen metsissä ja siten useat lahopuusta riippuvaiset lajit ovat päätyneet uhanalaisiksi. Lahopuun määrän lisäämiseksi metsähakkuiden yhteydessä on alettu jättämään säästöpuita ja tekopökkelöitä. Tekopökkelöt hyödyttävät lahotessaan lahopuusta riippuvaisia lajeja, kuten kolopesiviä myrkkypistiäisiä. Kolopesivät myrkkypistiäiset rakentavat pesänsä yleensä kovakuoriaisten puiden runkoihin kaivamiin koloihin. Tässä tutkimuksessa selvitettiin, millaista myrkkypistiäislajistoa tekopökkelöt tukevat, millaiset ja miten sijoitetut tekopökkelöt ovat hyödyllisimpiä myrkkypistiäisille, onko tekopökkelön vai ympäristön laatu merkittävämpää myrkkypistiäisille ja eroavatko eri ekologisten ryhmien (mesipistiäiset, petoina elävät myrkkypistiäiset ja pesäloiset) myrkkypistiäiset pesäpaikkavaatimuksiltaan. Tutkimuksen aineisto kerättiin kesällä 2021 Keski-Suomessa Viitasaarella, kuusivaltaisilta eri tavoin käsitellyiltä metsäkuviolta. Kuvioista kahdeksan oli harvennuksia, tuoreita päätehakkuita kahdeksan ja vanhoja päätehakkuita kymmenen. Tekopökkelöiden myrkkypistiäislajistoa tutkittiin keinopesien avulla. Keinopesät koostuivat muoviputkilosta, jonka sisällä oli eri kokoisia järviruo’on (Phragmites australis) korsia, monenlaisten myrkkypistiäislajien houkuttelemiseksi. Keinopesiä kiinnitettiin yhteensä 120 kappaletta teko- ja luonnonpökkelöihin, sekä kantoihin. Puulajeina oli kuusi ja koivu, sekä yksi haapa. Pökkelöistä ja metsäkuvioilta mitattiin niiden laatua kuvaavia muuttujia. Keinopesät olivat maastossa keväästä syksyyn, jolloin ne haettiin säilytykseen ulkovarastoon. Keinopesät siirrettiin huoneenlämpöön alkuvuonna 2022 pistiäisten aikuiseksi kehittymisen vauhdittamiseksi. Korret avattiin ja aikuiset myrkkypistiäiset tunnistettiin pesittäin lajilleen mikroskooppia apuna käyttäen. Tilastolliset analyysit suoritettiin R-Studiolla. Yksilö- ja lajimäärän muutoksia suhteessa selittäviin muuttujiin arvioitiin yleistetyillä lineaarisilla sekamalleilla (GLMM). Selittävinä muuttujina toimivat lämpötila, pökkelön korkeus, kaarnan peittävyys, alustan tyyppi, puulaji, lahopuun määrä, ravintokasvien määrä, hakkuutyyppi, pökkelön sijainti ja pesäkolojen määrä. Myrkkypistiäislajiyhteisöjen erilaisuutta arvioitiin NMDS-analyysillä. Sen avulla havainnollistettiin lajiyhteisöjen erilaisuutta eri hakkuutyyppien välillä. Keinopesistä löydettiin kolopesiviä myrkkypistiäisiä ja niiden myrkkypistiäispesäloisia yhteensä yli 3000 yksilöä. Petoina eläviä myrkkypistiäisiä löytyi eniten harvennusmetsistä, joissa oli alhaisempi lämpötila kuin tuoreilla ja vanhoilla päätehakkuilla. Mesipistiäisiä, jotka ruokailevat sekä toukka että aikuisvaiheessa medellä ja siitepölyllä, löytyi eniten tuoreilta ja vanhoilta päätehakkuilta. Näillä kuvioilla oli korkeamman lämpötilan lisäksi aurinkoisempaa ja enemmän ravintokasveja kuin harvennusmetsissä. Kaikkia myrkkypistiäisiä löytyi eniten korkeilta pökkelöiltä, joiden rungoilla oli vain vähän kaarnaa. Myrkkypistiäiset suosivat enemmän teko- ja luonnonpökkelöitä kuin kantoja. Pökkelön ympäristön ominaisuudet olivat kuitenkin tärkeämpiä kuin pökkelön ominaisuudet niin lajimäärälle kuin yksilörunsaudelle. Koska eri ekologisten ryhmien lajit suosivat erilaisia elinympäristöjä, tekopökkelöitä kannattaa jatkossakin tehdä sekä pääte- että harvennushakkuiden yhteydessä. Tekopökkelöitä tehdessä kannattaa myös huomioida niiden monipuolinen sijoittuminen reunoille ja keskelle hakkuuta, jotta niitä jää hakkuualueelle monenlaisiin ympäristöoloihin. Tekopökkelö tulisi katkaista mahdollisimman korkealta, sillä korkeisiin pökkelöihin mahtuu enemmän pesiä kuin mataliin ja matalat pökkelöt ovat alttiimpia kosteudelle, sekä pesien homehtumiselle kuin korkeat pökkelöt.

Climate change severely threatens ecosystem services and human well-being: vegetation and soils underneath it can be particularly vulnerable to climate warming. Soils hold the largest carbon stock in terrestrial ecosystems, and urban park soils, especially in cool climates, can hold remarkable carbon stocks and may be able to offset some atmospheric CO2 emissions. Land use changes, such as urbanization, influence soil organic carbon formation and soil carbon storages. In this study, I was interested whether three vegetation types (deciduous trees, conifers and lawn) differ in their capacity to store C in their rhizosphere, and whether this is affected by park size. I measured the proportion of tree canopy layer in class A park areas of the city of Helsinki, to estimate soil C storages of these areas and to examine C density (kg C m-2). Proportions of tree canopy layers in different park size groups were measured using QGIS and ortographs. Soil C storages were calculated using existing soil C data and average proportions of conifer and deciduous trees in parks of the city of Helsinki. Park size had a significant effect on proportion of the tree canopy coverage: canopy cover decreases with an increase in park size. Especially large parks are dominated by lawn. The average soil C densities in small, medium and large parks were 23.98 kg C m-2, 23.47 kg C m-2 and 23.15 kg C m-2, respectively. However, the overall proportion of conifer canopy in parks of the city of Helsinki is rather small, resulting in small differences in C densities between different park size categories, despite significant differences in tree canopy coverage between the three size groups. Most of the stored soil C in parks of the city of Helsinki are under lawn, even though it is the least efficient of the three studied vegetation types (deciduous trees, conifers, lawn) in soil C sequestration. Within a park size category and at park level, large parks store the highest amount of carbon per park. Even so, at the city level, the total amount of carbon is highest in the small parks due to their high number. Conifer trees associate with improved C sequestration to soils compared to deciduous trees and lawn. Increasing the amount of conifer trees in urban parks thus likely increase the important C storages of these soils. Results of this study highlight the importance of the contribution of urban parks and especially conifer trees in carbon sequestration. Future research related to urban soil C sequestration and the effects of vegetation type and climatic conditions is needed to better understand soil C accumulation and how the C sequestration of urban park soils could be enhanced.

Climate change impacts can substantially vary between regions, which requires regional decision-making on how to best moderate the adverse effects and seek potential benefits. However, actors can experience multiple barriers during climate change adaptation decision-making, which need to be overcome to enable more efficient and successful regional adaptation processes. This thesis aims to increase the knowledge on how actors can approach overcoming barriers to adaptation in a regional and cross-sectoral climate change adaptation decision-making process. A qualitative case study is conducted, which focuses on inspecting a regional climate change adaptation pilot project in the Finnish region of Pirkanmaa. Various regional and local actors participated to and collaborated on the project. The study constitutes of 11 expert interviews that are subjected to directed qualitative content analysis. The thesis utilises an analytical framework which leans on institutional theory and incorporates concepts from actor-centred institutionalism and empirical literature on barriers to and opportunities for adaptation, adaptive capacity, and adaptation decision-making processes. With the use of this framework, this thesis answers the research question of: What are the perceptions, preferences, and capabilities of the involved key actors regarding the regional climate change adaptation decision-making process in Pirkanmaa, Finland? This thesis discovers that the actors perceive mainly informational and institutional barriers to impede the decision-making process, in particular the understanding phase. Nevertheless, many of the barriers can be tackled during the process with both informational and institutional opportunities, in addition to social opportunities through the improvement of networks. The actors also have several preferences with regard to how the barriers should be overcome. Such preferences include clarifying the actors’ roles and responsibilities at the start of the understanding phase of decision-making, as well as ideas yet to be tested, such as unifying regional utilisation of adaptation-related data. The study does not manage to provide conclusive answers on the initial capabilities of the actors. Still, clear indications could be detected pertaining to the increase in elements of adaptive capacity, such as information, institutions, and skills, following from the numerous opportunities that the actors experienced. The explorative and descriptive results of this thesis bring new perspectives and an empirical contribution into the field of overcoming barriers to adaptation by focusing on climate change adaptation decision-making at the Finnish regional level. These findings can be used as a basis for upcoming research, but they can also be applied by various actors in designing current and upcoming climate change adaptation decision-making processes.

Women have exhibited higher levels of math anxiety (MA) compared to men. Despite the relationship between MA and sex differences being topic of interest for over twenty years, the focal point has mostly been on the psychological causes. This review investigates the biological underpinnings of the social phobia and identifies numerous possible correlates which could inform future efforts to support students experiencing math anxiety and encourage more females to pursue STEM related careers. Articles that investigated sex differences in the context of MA were selected for the study using PRISMA guidelines. Females were found to experience higher levels of math anxiety compared to males. Age was shown to influence the prevalence of MA between sexes, with sex differences in MA being more infrequent in children and increasing towards adulthood. The findings suggest that a diverse set of biological sex differences related to to brain function, cognition and sex hormones can, in part, explain the higher prevalence of MA among females and age-related deviations. By shedding light on possible biological factors contributing to sex differences in MA, this review represents a valuable step toward a more comprehensive understanding of this complex issue.

This thesis explores the relationship between energy justice and demand response electricity pricing schemes in the residential market. As energy retailers make the transition towards demand response contracts, many opportunities arise for justice and injustice. It is vital that consumers are protected from arising injustices, and that the benefits of demand response schemes are distributed across the population. I use a popular energy justice framework to evaluate the demand response schemes of three European electricity retailers for their adherence to the principles of energy justice. The eight evaluative criteria are availability, affordability, due process, good governance, sustainability, intragenerational equity, intergenerational equity and responsibility. The three retailers are Tibber, E.ON Next, and Helen. Through this evaluation, I demonstrate that novel developments in energy systems by some energy retailers can positively inform the policies and practices of conventional retailers. There is room for growth in customer communication, stakeholder involvement, and smart home integration. My evaluation shows that retailers are yet to meet the aspirations of energy justice with their demand response schemes, but the potential for promoting justice clearly exists. I conclude with a set of recommendations Helen can take to meet the goals of energy justice in their electricity contracts.

Climate change is one of the biggest challenges our planet and humanity are experiencing. The time window for finding ways to miti-gate carbon emissions is getting smaller and there is an urgent need to find solutions that aim not only to reduce greenhouse gas (GHG) emissions, but to address the complex problems of land use change, deforestation, loss of biodiversity, and inequality. REDD+ is a multi-objective initiative under UNFCCC designed to reduce GHG emissions through deforestation and forest degradation togeth-er with non-carbon co-benefits of livelihoods, poverty, biodiversity, and local peoples and indigenous peoples rights. By applying a Qualitative comparative analysis (QCA) this thesis compares 12 various REDD+ countries national political contexts and particularly REDD+ policies and measures over time in order to identify conditions that enable or hinder the countries from achieving results in reversing forest cover trajectories. All the countries analyzed here are tropical, developing, or emerging countries with a political commitment to REDD+ with characteristics that hinder carbon-effective, cost-efficient, and equitable (3E) implementation of REDD+. The thesis builds on three previous REDD+ qualitative comparative analyses of various REDD+ countries' progress in developing and implementing national REDD+ policies and measures. The analysis follows an underlining theoretical assumption that both insti-tutions and agencies affect the REDD+ policy outcome. The longitudinal data used in the analysis is based on expert assessments conducted in three various data collection rounds in 2012, 2014, and 2016. The results show a set of enabling conditions under which countries can achieve a positive outcome. The findings from the previous studies have highlighted the importance of already initiated policy change and effective forest legislation from the institutional context, and from the actor-centered policy arena, the presence of powerful coalitions and the availability of performance-based payments. Here, two enabling remote conditions are identified (1) pressure from the forest resources and (2) the presence of effective forest legislation. The pressure from the forest resources leads to a positive outcome together with (3) strong national ownership and politi-cal will combined with (4) performance-based payments or (5) REDD+ policies and measures. The effective forest legislation.leads away from business-as-usual practices towards a broader transformational change when combined with (6) powerful transformation-al coalitions and (7) inclusive policy processes. Policy relevance: Well over a decade has passed since REDD+ was launched in 2007 but the progress has been much slower than it was initially expected. The evidence on what works and what does not is essential to achieve the GHG reductions needed to keep the global warming below 2C. The findings from this study can guide towards more effective, efficient, and equitable REDD+ policy design formulation and implementation.

Tämä opinnäytetyö käsittelee uuden ympäristöseurantamenetelmän kehitystyötä. Hauruja (Fucus spp.) on seurattu Suomen rannikolla jo pitkään, mutta nykyisiin kartoitus- ja seurantamenetelmiin liittyy haasteita ja epätarkkuutta. Hauruvaltaiset elinympäristöt ovat uudessa uhanalaisuusarvioinnissa määritelty erittäin uhanalaisiksi. Tarvetta uusille seurantamenetelmille siis on. Drone-teknologia on kehittynyt ja halventunut viime vuosina, mikä on avannut uusia mahdollisuuksia hyödyntää kaukokartoitusta. Edulliset valokuvaamiseen tarkoitetut dronet mahdollistavat sekä ajallisesti että paikallisesti erittäin tarkkojen ilmakuvien tuottamisen. Näitä on maailmalla käytetty menestyksellisesti myös rannikon kartoituksessa ja seurannassa. Suomessa drone-kuvia ei kirjallisuuden perusteella ole käytetty makrolevien kartoitukseen tai seurantaan. Tämän tutkimuksen tarkoitus on selvittää, sopivatko tällaiset drone-kuvat hauruyhteisöjen kartoitukseen ja monitorointiin itäisellä Suomenlahdella sekä tuottaa tietoa menetelmän jatkokehitystä ajatellen. Kuvasin 22 merenranta-alueen reunaympäristön alkukesällä 2020. Kuvatuista alueista valitsin kahdeksan jatkotutkimuksiin, jotka kuvattiin uudelleen syksyllä 2020. Tällöin niiden alueelta kerättiin kuvatulkinnan tueksi 263 tukipistettä, joilta mitattiin veden syvyys ja arvioitiin haurujen esiintyvyys Drop-kuvausmenetelmällä. Rajasin ilmakuvilta näkyvät haurualueet ja vertasin niitä tukipisteaineistoon. Havaitsin, että 80 % havainnoista tieto luokittui oikein. Cohenin kappa -testin perusteella kohteiden välillä sekä eri syvyyksillä olevilla kasvustoilla oli suuria eroja havaintojen luotettavuudessa. Syvemmällä kuin 2,5 metrissä olevien haurukasvustojen erottaminen onnistui huomattavasti huonommin. Myös matalimman kasvuston (0 – 0,5 m) erottaminen oli hankalaa. Tulokset ovat lupaavat, mutta niiden perusteella menetelmää ei kuitenkaan vielä voi todeta toimivaksi, vaan lisätutkimuksia tarvitaan. Tämän tutkimuksen perusteella kehitystyötä kannattaa jatkaa käyttämällä tarkkaa paikkatietoa ilmakuvien ja tukipisteaineiston tuottamiseen sekä uusia kuvantamismenetelmiä, jotka kykenevät tuottamaan tavanomaista RGB-kameraa paremman erottelukyvyn. Drone- ja meritöiden turvallisuuden parantamiseksi tehtiin riskienhallintaprosessi, jossa tunnistin, analysoin sekä raportoin töihin liittyvät merkittävimmät riskit.

Breast cancer is globally the leading cause of death in women. ER positive, HER2 negative breast cancer is the most common subgroup, covering two thirds of all breast cancer cases. The different isoforms of ERα, ERα66 and ERα36 are responsible of genomic and non-genomic ER signaling respectively. Tamoxifen is one of the most used drugs in ERα+ breast cancer. As a SERM tamoxifen blocks the activity of ERα66, but plays as an agonist for ERα36, which is associated with tamoxifen resistance. Tamoxifen resistance concerns more than 25% patients with ERα+ breast cancer but the molecular mechanisms that lead to development of resistant disease remain uncovered. Thus, the aim of this thesis was to reveal how two different ERα isoforms are used and regulated in tamoxifen resistance in two commonly used ERα+ breast cancer cell lines MCF7 and T47D. We studied the effect of hormones to tamoxifen sensitivity and to utilization of ERα isoforms. Additionally, we compared the transcriptomics of resistant and parental cells in both cell lines and tested how inhibition of key regulators affect the sensitivity against tamoxifen. In this thesis we report that MCF7 and T47D cell lines obtain different mechanisms of tamoxifen resistance, and that the development of tamoxifen resistance is a parallel process with the cell identity switch from luminal to basal. The EZH2 is involved in maintaining the luminal progenitor type of mammary cells, whereas c-Myc is highly expressed in the resistant cell lines. Hence, EZH2 and c-Myc are key players in development of tamoxifen resistance and could be considered as therapy targets in ERα+ breast cancers.

Forests play a key role in mitigating climate change and maintaining biodiversity. The ability of forests to sequester carbon dioxide and store it in wood biomasses and soils reduces the amount of carbon dioxide in the atmosphere. However, forests are cut down for various reasons, such as economic ones, releasing carbon dioxide from the trees into the atmosphere. One way to combat climate change and biodiversity loss is to provide forest owners a voluntary incentive scheme that provides a new objective for forest owners to use their forests. The use of forests in the future will be decided by the new forest owners, i.e., the younger generation of forest owners. For this reason, it’s important to study their preferences for a voluntary incentive scheme. The study examined the characteristics of absentee and non-absentee forest owners under the age of 40 and compared the preferences for a voluntary incentive scheme directed to these two groups. The survey response rate was low (7,3%). Choice experiment method and a binary logistic regression model was used to find out the forest owners’ preferences in relation to accept the programme. In the binary logistic regression model, absentee residence was the only factor that positively and reliably increases the acceptance of the programme. Absentee and non-absentee forest owners appreciate similar aspects of forest property, for example relaxation and financial security. The biggest difference between these two groups came with consideration of forestry work and/or wood for household as nonabsentee forest owners valued that aspect higher. The study points out that knowledge of a METSO programme is relatively low, as 35% of absentee and 23% of non-absentee forest owners who responded have heard of the programme. Some young forest owners may not have a clear idea on how to manage forests, because forest ownership is new to them and therefore it is often difficult for novice forest owners to know which forest management practices to apply in one's own forests. According to the study, economic income from the forest property is important, but it isn’t an important source of economic security for a large number of young forest owners, especially when the share of absentee forest owners’ characteristics and preferences are on the rise among forest owners.