Lipase-catalyzed Approaches towards Secondary Alcohols: Intermediates for Enantiopure Drugs

The use of enantiopure intermediates for drug synthesis is a trend in pharmaceutical industry. Different physiological effects are associated with the enantiomers of chiral molecules. Thus, the safety profile of a drug based on an enantiopure active pharmaceutical ingredient is more reliable. Biocatalysis is an important tool to access enantiopure molecules. In biocatalysis, the advantage of selectivity (chemo-, regio- and stereoselectivity) is combined with the benefits of a green synthesis strategy. Chemoenzymatic syntheses of drug molecules, obtained by combining biocatalysis with modern chemical synthesis steps usually consists of fewer reaction steps, reduced waste production and improved overall synthetic efficiency both in yields and enantio- and/or diastereoselectivities compared with classical chemical synthesis. The experimental work together with the literature review clearly indicates that lipase catalysis is highly applicable in the synthesis of enantiopure intermediates of drug molecules as the basis to infer the correct stereochemistry. By lipase catalysis, enantiopure secondary alcohols used as intermediates in the synthesis of Dorzolamide, an antiglaucoma drug, were obtained. Enantiopure _-hydroxy nitriles as potential intermediates for the synthesis of antidepressant drugs with 1-aryl-3- methylaminopropan-1-ol structure were also obtained with lipases. Kinetic resolution of racemates was the main biocatalytic approach applied. Candida Antarctica lipase B, Burkholderia cepacia lipase and Thermomyces lanuginosus lipase were applied for the acylation of alcohols and the alcoholysis of their esters in organic solvents, such as in diisopropyl ether and tert-butyl methyl ether. Candida Antarctica lipase B was used under solvent free conditions for the acylation of ethyl 3-hydroxybutanoate.

Middle school mediocrity : quality and inequality in secondary education

Centrala teman i min avhandling är parallellskolesystem, linjedelning och segregering i högstadier och gymnasier. Det finns stora skillnader mellan länder gällande den årskurs då eleverna sorteras in i olika nivåer genom skilda klasser eller skolor. I Tyskland och Nederländerna till exempel delas eleverna upp före högstadiet medan Sverige och Finland har enhetsskolor på högstadienivå. Jag argumenterar att parallellskolesystem har en positiv effekt på elevernas testresultat i årskurserna före linjedelningen. Eleverna har incitament att jobba hårdare för att komma på i den akademiska linjen. Jag undersöker incitamentseffekter empiriskt, och hittar mönster konsistenta med incitamentseffekter både i brittisk och i internationell data. Det andra bidraget i avhandlingen är metodologiskt. Nationalekonomer brukar behandla testresultat från t.ex. IQ-tester eller internationella PISA-undersökningar som om absoluta nivån på poängantalen har betydelse i sig. I verkligheten antyder de endast en rangordning. Jag visar att normalfördelade testresultat i många fall ligger tillräckligt nära dess pengavärde på arbetsmarknaden för att ändå kunna tolkas som absoluta.

Pragmatic competence of Finnish learners of English: Meaning in interaction in secondary and upper secondary schools

Tutkin pro gradu -tutkielmassani englannin kielen oppijoiden pragmaattista kompetenssia. Tarkoitukseni oli selvittää, miten suomalaiset yläkoululaiset ja lukiolaiset osaavat käyttää englannin kieltä erilaisissa kommunikaatiotilanteissa. Tutkielmani voidaan sijoittaa välikielen pragmatiikan tutkimukseen. Halusin selvittää, millä tasolla suomalaisten oppijoiden pragmaattinen kompetenssi on ja kehittyykö se yläkoulun ja lukion välillä. Lisäksi tutkin, vaikuttavatko oppimisympäristö ja oppimismahdollisuudet oppijoiden kykyyn käyttää englannin kieltä. Toisin sanoen vertasin englantipainotteisilla luokilla olevia oppilaita formaalin opetuksen oppijoihin sekä tutkin, vaikuttavatko englanninkieliset vapaa-ajan aktiviteetit ja oppijoiden mahdolliset oleskelut englanninkielisissä maissa heidän pragmaattiseen kompetenssiinsa. Tutkimukseni kohderyhmä koostui yläkoulun kahdeksasluokkalaisista ja lukion toisen vuosikurssin opiskelijoista. Testasin neljä eri ryhmää, joissa oli sekä formaalissa opetuksessa olevia oppijoita (yksi ryhmä kahdeksasluokkalaisia ja yksi ryhmä toisen vuosikurssin opiskelijoita) että kielipainotteisten luokkien oppijoita (yksi ryhmä kahdeksasluokkalaisia ja yksi ryhmä toisen vuosikurssin opiskelijoita). Arvioin kohderyhmäni pragmaattista kompetenssia monivalintatestillä, jossa testattiin oppijoiden kykyä käyttää ja ymmärtää implikaatioita, tilannekohtaisia rutiineja sekä puheakteja. Taustakysymysten avulla selvitin, kuinka usein oppijat käyttivät englantia vapaa-aikanaan ja olivatko he vierailleet englanninkielisissä maissa. Tutkimustulokseni osoittavat, että suomalaisten yläkoululaisten ja lukiolaisten pragmaattinen kompetenssi oli korkea. Pragmaattinen kompetenssi kehittyi kahdeksasluokkalaisten ja lukion toisen vuosikurssin välillä. Kehitys oli suurempaa formaalissa opetuksessa kuin kielipainotteisilla luokilla. Englantipainotteisilla luokilla olevat oppilaat suoriutuivat testistä paremmin kuin formaalin opetuksen oppilaat. Tosin erot olivat tilastollisesti merkitseviä vain yläkoulussa. Tutkimuksessani siis päättelin, että vieraskielinen opetus vaikutti enemmän nuorempiin oppijoihin. Eri oppimismahdollisuudet osoittautuivat haastaviksi analysoida. Tulokset osoittivat, että vain englanninkielisessä maassa oleskelulla oli vaikutusta oppijoiden pragmaattiseen kompetenssiin. Kysyttäessä vapaa-ajan aktiviteettien merkitystä oppijat kuitenkin kertoivat, että ne auttoivat heitä testiin vastaamisessa enemmän kuin englanninopetuksessa käydyt asiat. Kouluissa tulisikin jatkossa painottaa yhä enemmän vuorovaikutteista kieltenopetusta.

Battery Cell Modeling for Battery Management System

Usage of batteries as energy storage is emerging in automotive and mobile working machine applications in future. When battery systems become larger, battery management becomes an essential part of the application concerning fault situations of the battery and safety of the user. A properly designed battery management system extends one charge cycle of battery pack and the whole life time of the battery pack. In this thesis main objectives and principles of BMS are studied and first order Thevenin’s model of the lithium-titanate battery cell is built based on laboratory measurements. The battery cell model is then verified by comparing the battery cell model and the actual battery cell and its suitability for use in BMS is studied.

Understanding and improving quality of secondary school education : conceptions among teachers in Tanzania

Temat för studien handlar om gymnasielärares uppfattningar om kvalitet och om hur kvalitet kan utvecklas i gymnasieutbildningen in Tanzania. Studien är till sin karaktär kvalitativ och består av utprövade semistrukturerade intervjuer med sammanlagt trettio lärare som arbetar i fyra gymnasieskolor både i urbana och rurala miljöer. Lärarna har varierande arbetserfarenhet och undervisar i olika ämnen. Huvudfokus har gällt identifieringen av variationer i lärares uppfattningar om kvalitet. På basen av två forskningsfrågor avslöjar analysen uppfattningar av hur lärare förstår och önskar utveckla kvaliteten på gymnasieutbildningen. Resultaten visar att lärare förstår kvaliteten på utbildningen i sina skolor som försök att möta skolans och samhällets mål, som individuella prestationer och förmågor som att inneha kompetenser och som att möta utmaningar inom utbildning, Identifierade uppfattningar var baserade på lärarnas personliga kunskap, arbetsmiljön och varierande omständigheter som rådde i deras skolor. Uppfattningar om en förbättring av kvaliteten i gymnasieutbildningen innefattade utveckling av lärares motivation, skolmiljön, arbetet i klassrum, kvaliteten på lärares kunskaper och färdigheter och undervisningsmaterial. Ambitionen bakom studien ar att erbjuda en plattform för strategier för att förbättra kvaliteten på gymnasieutbildningen. Resultaten strävar till att ge en fördjupad insikt i uppfattningar hos en utvald grupp av lärare som arbetar under samma villkor inom gymnasieskolor I Tanzania. Av den här anledningen är den genererade kunskapen därför relevant för att belysa lärares uppfattningar även utanför den studerade gruppen av respondenter.

Hydrometallurgical recovery of valuable metals from secondary raw materials

Wastes and side streams in the mining industry and different anthropogenic wastes often contain valuable metals in such concentrations their recovery may be economically viable. These raw materials are collectively called secondary raw materials. The recovery of metals from these materials is also environmentally favorable, since many of the metals, for example heavy metals, are hazardous to the environment. This has been noticed in legislative bodies, and strict regulations for handling both mining and anthropogenic wastes have been developed, mainly in the last decade. In the mining and metallurgy industry, important secondary raw materials include, for example, steelmaking dusts (recoverable metals e.g. Zn and Mo), zinc plant residues (Ag, Au, Ga, Ge, In) and waste slurry from Bayer process alumina production (Ga, REE, Ti, V). From anthropogenic wastes, waste electrical and electronic equipment (WEEE), among them LCD screens and fluorescent lamps, are clearly the most important from a metals recovery point of view. Metals that are commonly recovered from WEEE include, for example, Ag, Au, Cu, Pd and Pt. In LCD screens indium, and in fluorescent lamps, REEs, are possible target metals. Hydrometallurgical processing routes are highly suitable for the treatment of complex and/or low grade raw materials, as secondary raw materials often are. These solid or liquid raw materials often contain large amounts of base metals, for example. Thus, in order to recover valuable metals, with small concentrations, highly selective separation methods, such as hydrometallurgical routes, are needed. In addition, hydrometallurgical processes are also seen as more environmental friendly, and they have lower energy consumption, when compared to pyrometallurgical processes. In this thesis, solvent extraction and ion exchange are the most important hydrometallurgical separation methods studied. Solvent extraction is a mainstream unit operation in the metallurgical industry for all kinds of metals, but for ion exchange, practical applications are not as widespread. However, ion exchange is known to be particularly suitable for dilute feed solutions and complex separation tasks, which makes it a viable option, especially for processing secondary raw materials. Recovering valuable metals was studied with five different raw materials, which included liquid and solid side streams from metallurgical industries and WEEE. Recovery of high purity (99.7%) In, from LCD screens, was achieved by leaching with H2SO4, extracting In and Sn to D2EHPA, and selectively stripping In to HCl. In was also concentrated in the solvent extraction stage from 44 mg/L to 6.5 g/L. Ge was recovered as a side product from two different base metal process liquors with Nmethylglucamine functional chelating ion exchange resin (IRA-743). Based on equilibrium and dynamic modeling, a mechanism for this moderately complex adsorption process was suggested. Eu and Y were leached with high yields (91 and 83%) by 2 M H2SO4 from a fluorescent lamp precipitate of waste treatment plant. The waste also contained significant amounts of other REEs such as Gd and Tb, but these were not leached with common mineral acids in ambient conditions. Zn was selectively leached over Fe from steelmaking dusts with a controlled acidic leaching method, in which the pH did not go below, but was held close as possible to, 3. Mo was also present in the other studied dust, and was leached with pure water more effectively than with the acidic methods. Good yield and selectivity in the solvent extraction of Zn was achieved by D2EHPA. However, Fe needs to be eliminated in advance, either by the controlled leaching method or, for example, by precipitation. 100% Pure Mo/Cr product was achieved with quaternary ammonium salt (Aliquat 336) directly from the water leachate, without pH adjustment (pH 13.7). A Mo/Cr mixture was also obtained from H2SO4 leachates with hydroxyoxime LIX 84-I and trioctylamine (TOA), but the purities were 70% at most. However with Aliquat 336, again an over 99% pure mixture was obtained. High selectivity for Mo over Cr was not achieved with any of the studied reagents. Ag-NaCl solution was purified from divalent impurity metals by aminomethylphosphonium functional Lewatit TP-260 ion exchange resin. A novel preconditioning method, named controlled partial neutralization, with conjugate bases of weak organic acids, was used to control the pH in the column to avoid capacity losses or precipitations. Counter-current SMB was shown to be a better process configuration than either batch column operation or the cross-current operation conventionally used in the metallurgical industry. The raw materials used in this thesis were also evaluated from an economic point of view, and the precipitate from a waste fluorescent lamp treatment process was clearly shown to be the most promising.

Studies in selectivity of lipases in preparation of cyanohydrins, sugar conjugates and secondary alcohols

Biocatalysis can be applied in organic synthetic chemistry to counter challenges posed by increased demands towards chemo-, regio- and stereoselectivity, not forgetting the need for greener chemistry. During the last 30 years, biocatalysis with the use of enzymes as chiral catalysts has become more common in chemistry laboratories and industrial processes. In this thesis, the use of lipases as versatile biocatalysts in the acylation of alcohols is examined both in the light of literature examples and four original publications. In the first part of the work presented in this thesis lipases were utilized in two examples concerning secondary alcohols. First, the kinetic resolution of heterocyclic aromatic secondary alcohols through transesterification was thoroughly examined including the studies of competing hydrolysis and esterification reactions. In another example, lipases were utilized in the formation of a dynamic systemic resolution (DSR) process which in turn was used as a developmental tool in the optimization of the dynamic kinetic resolution (DKR) of five heterocyclic aromatic cyanohydrins in one pot for the preparation of cyanohydrin esters as single enantiomers. In the second part of the work, the regio- and stereoselectivity of lipases was used to form sugar conjugates of glyceric and β-amino acids. The primary hydroxyl groups of methyl α-D-galacto-, -gluco- and -mannopyranosides were now acylated trough lipasecatalyzed transesterification and enantioselective lipase-catalyzed ring-opening of β- lactams, respectively.

Entrepreneurship Education in Basic and Upper Secondary Education – Measurement and Empirical Evidence

The starting point of this study is to direct more attention to the teacher and those entrepreneurship education practices taking place in formal school to find out solutions for more effective promotion of entrepreneurship education. For this objective, the strategy-level aims of entrepreneurship education need to be operationalised into measurable and understandable teacher-level practices. Furthermore, to enable the effective development of entrepreneurship education in basic and upper secondary level education, more knowledge is needed of the state of affairs of entrepreneurship education in teaching. The purpose of the study is to increase the level of understanding of teachers’ entrepreneurship education practices, and through this to develop entrepreneurship education. This study builds on the literature on entrepreneurship education and especially those elements referring to the aims, resources, benefits, methods, and practises of entrepreneurship education. The study comprises five articles highlighting teachers’ role in entrepreneurship education. In the first article the concept of entrepreneurship and the teachers role in reflection upon his/hers approaches to entrepreneurship education are considered. The second article provides a detailed analysis of the process of developing a measurement tool to depict the teachers’ activities in entrepreneurship education. The next three articles highlight the teachers’ role in directing the entrepreneurship education in basic and upper secondary level education. Furthermore, they analyse the relationship between the entrepreneurship education practises and the teachers’ background characteristics. The results of the study suggest a wide range of conclusions and implications. First, in spite of many outspoken aims connected to entrepreneurship education, teachers have not set any aims for themselves. Additionally, aims and results seem to mix. However, it is possible to develop teachers’ target orientation by supporting their reflection skills, and through measurement and evaluation increase their understanding of their own practices. Second, applying a participatory action process it is possible to operationalise teachers’entrepreneurship education practices. It is central to include the practitioners’ perspective in the development of measures to make sure that the concepts and aims of entrepreneurship education are understood. Third, teachers’ demographic or tenure-related background characteristics do not affect their entrepreneurship education practices, but their training related to entrepreneurship education, participation in different school-level or regional planning, and their own capabilities support entrepreneurship education. Fourth, a large number of methods are applied to entrepreneurship education, and the most often used methods were different kinds of discussions, which seem to be an easy, low-threshold way for teachers to include entrepreneurship education regularly in their teaching. Field trips to business enterprises or inviting entrepreneurs to present their work in schools are used fairly seldom. Interestingly, visits outside the school are more common than visitors invited to the school. In line, most of the entrepreneurship education practices take place in a classroom. Therefore it seems to be useful to create and encourage teachers towards more in-depth cooperation with companies (e.g. via joint projects) and to network systematically. Finally, there are plenty of resources available for entrepreneurship education, such as ready-made materials, external stakeholders, support organisations, and learning games, but teachers have utilized them only marginally.

Keskitehoestimaattorin lisääminen diesel-sähköiseen hybridijärjestelmään

Nykyajan jatkuvasti kiristyvät päästörajoitukset ja ilmastonmuutoksen uhka ovat ajavia voimia kehittämään voimalaitosten tekniikkaa energiatehokkaampaan ja ympäristöystävällisempään suuntaan. Polttomoottoritekniikan parantaminen on tärkeä osa tätä kehitystä, mutta jo nykyisiä moottoreita voitaisiin ajaa energiate-hokkaammin käyttämällä akustoa ja älykästä säätöjärjestelmää apuna. Työssä tutkitaan simulaatioiden avulla voidaanko ulkomerellä toimivan huolto-aluksen energiatehokkuutta parantaa muokkaamalla sen tehon tuottoa keskitehoes-timaattorin ja akuston avulla.

Vanadiiniakut

Nykyään monet käyttökohteet vaativat akuilta aiempaa parempaa suorituskykyä, joten on syntynyt kasvavaa tarvetta uusien akkujen kehittämiselle erilaisista uusista materiaaleista ja uusiin valmistusmenetelmiin pohjautuen. Työn tavoitteena on selvittää kirjallisuustutkimuksena litium-vanadiini-fosfaattiakun ja vanadiini-redoksi-virtausakun ominaisuuksia, saatavuutta, sovelluskohteita ja vertailla niitä muutamaan eri litiumakkutekniikkaan. Tutkimuksen perusteella litium-vanadiini-fosfaattiakkuja ei ole vielä saatavilla kaupallisesti, joten työssä tutkittiin niitä teknisten raporttien pohjalta. Raporttien pohjalta arvioituna, parhaita ominaisuuksia litium-vanadiini-fosfaattiakuilla on erinomainen kuormituksen kesto ja korkea nimellisjännite. Sähköisissä ajoneuvoissa litium-vanadiini-fosfaattiakuilla on suurimmat mahdollisuudet erilaisissa hybridiajoneuvoissa, mutta todennäköisesti ne soveltuvat täyssähköisiin ajoneuvoihin vähintään yhtä hyvin kuin esimerkiksi litium-rauta-fosfaattiakut, jos valmistuskustannukset olisivat samalla tasolla. Vanadiini-redoksi-virtausakkua on jo markkinoilla usean valmistajan toimesta. Niiden ominaisuudet poikkeavat paljon muista akkutyypeistä ja erikoisuutena on mahdollisuus akun pikalataukseen elektrolyyttinesteet vaihtamalla. Syklien kestossa päästään myös erinomaisiin arvoihin, mutta suurimmat ongelmat ovat lyijyakkuakin matalampi energiatiheys ja tehotiheys. Vanadiini-redoksi-virtausakut soveltuvat parhaiten suuren kokoluokan sähköverkkoratkaisuihin ja sähköisissä ajoneuvoissa niiden mahdollisuudet rajoittunevat täyssähköisiin linja-autoihin ja isoihin työkoneisiin.

Continuous Counter-current Solvent Extraction of Magnesium and Calcium from Lithium-rich Brine

Solvent extraction of calcium and magnesium impurities from a lithium-rich brine (Ca ~ 2,000 ppm, Mg ~ 50 ppm, Li ~ 30,000 ppm) was investigated using a continuous counter-current solvent extraction mixer-settler set-up. The literature review includes a general review about resources, demands and production methods of Li followed by basics of solvent extraction. Experimental section includes batch experiments for investigation of pH isotherms of three extractants; D2EHPA, Versatic 10 and LIX 984 with concentrations of 0.52, 0.53 and 0.50 M in kerosene respectively. Based on pH isotherms LIX 984 showed no affinity for solvent extraction of Mg and Ca at pH ≤ 8 while D2EHPA and Versatic 10 were effective in extraction of Ca and Mg. Based on constructed pH isotherms, loading isotherms of D2EHPA (at pH 3.5 and 3.9) and Versatic 10 (at pH 7 and 8) were further investigated. Furthermore based on McCabe-Thiele method, two extraction stages and one stripping stage (using HCl acid with concentration of 2 M for Versatic 10 and 3 M for D2EHPA) was practiced in continuous runs. Merits of Versatic 10 in comparison to D2EHPA are higher selectivity for Ca and Mg, faster phase disengagement, no detrimental change in viscosity due to shear amount of metal extraction and lower acidity in stripping. On the other hand D2EHPA has less aqueous solubility and is capable of removing Mg and Ca simultaneously even at higher Ca loading (A/O in continuous runs > 1). In general, shorter residence time (~ 2 min), lower temperature (~23 °C), lower pH values (6.5-7.0 for Versatic 10 and 3.5-3.7 for D2EHPA) and a moderately low A/O value (< 1:1) would cause removal of 100% of Ca and nearly 100% of Mg while keeping Li loss less than 4%, much lower than the conventional precipitation in which 20% of Li is lost.

Akkuvarastot omakotitaloissa

Energian varastointi on noussut keskeiseksi energia-alan teemaksi viime vuosina. Erityi-sesti uusiutuvan tuotannon lisääntyminen ja energian käytön tehostaminen ovat edesautta-neet energiavarastoratkaisuiden mukaantuloa. Työssä tarkastellaan litiumrautafosfaattiak-kujen käytön kannattavuutta omakotitaloissa. Tavoitteena on selvittää, millä reunaehdoilla näiden akkujen käyttö energiavarastoina tulee kannattavaksi Lappeenrannan olosuhteissa. Kannattavuutta selvitetään litiumrautafosfaattiakkujen markkina-analyysin ja teknistalou-dellisen analyysin sekä Matlab-simulaation avulla.