Kodin ja työn rajavyöhykkeellä - yhteensovittamisen jännitteitä ja ratkaisuja arjessa

The aim of this research is to study the boundary zone of home and work and the tensions people experience while reconciling home and work? How are the requirements of the family, the home and the work taken care of in everyday life? What kind of difficulties does the individual experience when reconciling home activities and job requirements together? What kind of activity policies have families created to ease the everyday life? What kind of goals and requirements do families feel behind the difficulties in adjusting home and work? What kind of changes would make the adjusting of home and work easier? The changing family life, everyday home activities and the changing Finnish working life are studied to describe the adjusting of home and work. In addition the boundary zone of home and work and its tensions are studied. 337 research persons who find reconciling home and work challenging were elected from different sectors of the working life. Research persons were gathered from the public, private and third sectors. The research material was gathered with a semi-structured qualitative questionnaire published in internet. Contents analysis was the analysis method of the research material. The tensions of adjusting home and work are various. Several activity systems meet on the boundary zone of home and work causing boundary zones to expand and tensions to increase and expand like a network. In the everyday life of an individual the boundary zone fades out and home and work overlap. Tensions can be examined as internal conflicts of the individual through the activity system of everyday life. Individuals balance between individualism and familism, feeling bad, suffering from lack of time and struggling with childcare organizing problems and inflexible employers. The solutions to reconciling home and work difficulties are situational. Often is the help of family and friends required without any solid solutions. The conflict of the goals, requirements and the reality is behind the problems as well as the tightening terms of the working life and its growing expectations. Change requests are proposed on the levels of individual, home, work and the society. Reconciling home and work is not only a challenge between the employee and the employer. It s a problem that needs multilateral solutions and changes on the levels of individual, home, work and society. The challenge remaining is to find out if it would be successful to take the everyday life as starting point to negotiate the reconciling of home and work and how the possible family, social and work political solutions appear in everyday life.

Nashin tasapainon löytämisen laskennallinen vaativuus

Tässä tutkielmassa käsitellään approksimatiivisen Nashin tasapainon löytämisongelmaa laskennallisen vaativuuden kannalta. Vaikka Nashin tasapainon tiedetään olevan aina olemassa, on tasapainon löytäminen osoittautunut vaikeaksi ongelmaksi. Approksimatiivisen Nashin tasapainon löytämisongelma on PPAD-ongelmaluokan täydellinen ongelma. PPAD-luokkaan kuuluvat sellaiset etsintäongelmat, joissa etsittävän ratkaisun olemassaolo seuraa suunnattujen graafien pariteettiargumentista. Suunnattujen graafien pariteettiargumentti toteaa, että jos graafin jokaisen solmun lähtö- ja tuloasteet ovat korkeintaan yksi ja graafissa on tunnettu lähdesolmu, niin graafissa on myös nielusolmu tai toinen lähdesolmu. PPAD-täydellisyyden takia on luultavaa, ettei approksimatiivista Nashin tasapainoa voi löytää polynomisessa ajassa. Tässä kirjoituksessa esitetään uudelleenmuotoiltu ja tarkennettu versio approksimatiivisen Nashin tasapainon löytämisongelman PPAD-vaikeustodistuksesta. Lisäksi esitetään todistus ongelman kuulumiselle luokkaan PPAD. Vastaavaa todistusta ei löydy kirjallisuudesta, vaikka approksimatiivisen Nashin tasapainon löytämisongelman kuuluminen luokkaan PPAD mainitaan.

Matrix Decomposition Methods for Data Mining : Computational Complexity and Algorithms

Matrix decompositions, where a given matrix is represented as a product of two other matrices, are regularly used in data mining. Most matrix decompositions have their roots in linear algebra, but the needs of data mining are not always those of linear algebra. In data mining one needs to have results that are interpretable -- and what is considered interpretable in data mining can be very different to what is considered interpretable in linear algebra. --- The purpose of this thesis is to study matrix decompositions that directly address the issue of interpretability. An example is a decomposition of binary matrices where the factor matrices are assumed to be binary and the matrix multiplication is Boolean. The restriction to binary factor matrices increases interpretability -- factor matrices are of the same type as the original matrix -- and allows the use of Boolean matrix multiplication, which is often more intuitive than normal matrix multiplication with binary matrices. Also several other decomposition methods are described, and the computational complexity of computing them is studied together with the hardness of approximating the related optimization problems. Based on these studies, algorithms for constructing the decompositions are proposed. Constructing the decompositions turns out to be computationally hard, and the proposed algorithms are mostly based on various heuristics. Nevertheless, the algorithms are shown to be capable of finding good results in empirical experiments conducted with both synthetic and real-world data.

Sairaanhoitajat työn imussa? Palkkatyön sisällön ja kulttuuristen lähtökohtien tasapainossa

Tutkimuksen tavoitteena on selvittää, mikä saa pitkän työuran tehneet sairaanhoitajat innostumaan työstään. Taustalla on yhteiskunnallinen tilanne, jossa työelämän vetovoimaisuuden lisääminen ja ikääntyvien työntekijöiden työssä jaksaminen ovat keskeisiä poliittisia tavoitteita. Aihetta lähestytään positiivisesta psykologiasta lähtöisin olevan työn imun käsitteen avulla. Se on määritelty pysyväksi, ”myönteiseksi, tunne- ja motivaatiotäyttymyksen tilaksi, jota luonnehtivat tarmokkuus, omistautuminen ja uppoutuminen työhön” (Hakanen 2009a, 9). Tutkimuksessa kysytään, voidaanko työn imua ymmärtää myös sosiologisesta näkökulmasta. Oletuksena on, että käsitteen taustalla on muutakin kuin psykologisesta perinteestä käsin jäsentyvää vaihtelua. Empiirisen aineiston muodostavan 11 sairaanhoitajan koko työuraa ja nykyistä työtä koskevat tiettyihin teemoihin ankkuroidut syvähaastattelut. Otosta poimittaessa on etsitty sellaisia haastateltavia, jotka kokevat kantavansa työn imua. Aineiston analyysitapana on käytetty matriisin avulla sovellettua kvalitatiivista sisällönanalyysiä. Työn imua hahmotetaan analyysissä henkilöhistoriallisten haastatteluiden – menneen, nykyisen ja tulevan – kautta. Pyrkimyksenä on etsiä tarinoita mahdollisesti yhdistävää kulttuurista muotoa ja ymmärtää, mihin se perustuu. Analyysin nojalla vastuurationaalisuuden käsite (esim. Korvajärvi 1986) näyttäisi jäsentävän osan haastateltavien suhteesta työhönsä. Avain työn imun löytymiseen näissä tarinoissa on kuitenkin se, kuinka haastateltavilla on ollut henkilökohtainen halu mennä eteenpäin ja kykyä ratkaista ongelmia työuransa aikana ja nykyisessä työssään. Tämä havainto tulkitaan Max Weberin (1922, 1980) käsitteiden – arvorationaalisen ja päämäärärationaalisen toiminnan väliseen suhteen – avulla. Tulokseksi syntyy oletus siitä, että analyysin kohteena olevissa tarinoissa on kyse yhteisestä kulttuurisesta tarinasta siitä, millainen on hyvä ihminen, miten hyvä ihminen toteuttaa itseään työssä ja miten hän tekee työtään: tarmokkaasti, omistautuen ja uppoutuen. Henkilökohtainen halu mennä eteenpäin ja kyky ratkaista ongelmia nojaa sairaanhoitajien erityiseen eetokseen, kutsumustyöhön ja hoivan moraaliin tavalla, joka on rakenteellisesti yhtäläinen protestanttisuutta leimaavan yksilöllisen jumalasuhteen kanssa. Lisäksi analyysin perusteella esitetään, että työn imun edellytys on arvorationaalisen eetoksen lisäksi oikeanlainen, riittävät työn voimavarat sisältävä ympäristö, jossa hoitotyön keskeiset palkinnot on mahdollista saavuttaa. Tällöin palkkatyön sisältö kohtaa kulttuuriset lähtökohdat, ja tulos näkyy työn imuna. Keskeisimmät taustoittavat lähteet ovat Henriksson, Lea & Wrede, Sirpa (toim.) (2004a). Hyvinvointityön ammatit ja Hakanen, Jari (2009a). Työn imun arviointimenetelmä (Utrecht Work Engagement Scale). Sosiologisen tulkinnan kannalta tärkein teoreettinen lähde on Weber, Max (1980): Protestanttinen etiikka ja kapitalismin henki.

Koulun kestävän kehityksen työn merkitys kiinteistön jätehuollossa Case: Helsingin peruskoulujen jätekustannukset ja -määrät

Koulujen kestävän kehityksen työllä tarkoitetaan ekologiseen, taloudelliseen, sosiaaliseen ja kulttuuriseen kestävyyteen pohjautuvaa ympäristökasvatusta. Helsingissä peruskoulujen kestävän kehityksen työvälineet (ympäristökartoitukset ja – ohjelmat) ovat perustuneet koulujen ympäristöasioiden suunnitteluun, opetussuunnitelmien toteutumiseen ja ylläpitotoimintoihin, kuten jätehuoltoon. Opetusvirasto käytti vuosina 2005 ja 2009 ympäristötoiminnan arvioinnissa ympäristötasokuvauksia 1-3, joista arvosana 3 kuvaa ympäristöasioissa edistyneintä koulua. Tutkielman tavoitteena on tutkia ympäristötoiminnan tasojen perusteella ryhmiteltyjen peruskoulujen välisiä eroja jätekustannuksissa ja – määrissä (euroa/henkilö ja kg/henkilö) ja löytää mahdollisesti eroihin vaikuttavia tekijöitä. Tutkielman toimeksiantajana on 4V-Välitä, vaikuta, viihdy, voi hyvin – hanke, jonka yhtenä toiminnan osa-alueena on koulujen kestävän kehityksen työ. Tuloksista tullaan johtamaan tietoa Opetusviraston sekä muiden tahojen, kuten HSY:n ja Palmian ympäristötyöhön sekä Kiinteistöviraston Tilakeskuksen hallinnassa olevien koulukiinteistöjen jätehuollon kehittämiseen. Tutkimusaineistoina käytettiin Helsingin peruskoulujen vuoden 2009 jätekustannuksia ja tutkielman yhteydessä kerätyn jäteseurannan tuloksia vuodelta 2010. Jätekustannus- ja jätemääräaineistot yhdistettiin vuoden 2009 ympäristötoiminnan tasoluokitusten perusteella otokseksi (n=64). Lopullinen jätekustannus- ja jätemääräanalyysi tehtiin 29 koulun otoksella, josta oli rajattu pois kiinteistöt, joilla on koulun toiminnan lisäksi muita käyttötarkoituksia. Analyysiin sisällytettiin myös tarkempi tarkastelu koulujen seka- ja biojätejakeiden kustannuksista ja määristä. Tutkimuksen johtopäätöksenä todettiin, että eri ympäristötasoisten peruskoulujen välillä on huomattavia euro- ja kilomääräisiä eroja henkilöä kohden lasketuissa jätekustannuksissa ja –määrissä. Kokonaisjätemäärässä ei ole tapahtunut merkittävää muutosta tarkasteluvuosien välillä, mutta lajittelu näyttäisi kuitenkin tehostuneen. Tulosten perusteella ympäristöasioissa edistyneiden tason 3 koulujen keskimääräiset sekajätemäärät ja -kustannukset olivat pienimmät tasojen 1 ja 2 kouluihin verrattuna. Biojätemäärät ja –kustannukset olivat suurimmat tason 2 kouluissa. Jätekustannuksiin ja – määriin näyttäisivät vaikuttavan jäteastioiden määrien, kokojen ja tyhjennysrytmien optimointi sekä jäteastioiden täyttöasteet. Peruskoulujen tulisi keskittyä kestävän kehityksen työn avulla jätteiden synnyn ehkäisyyn ja vähentämiseen, jotta jätekustannuksetkin vähentyisivät jätehuollon kehittämistoimenpiteiden seurauksena.

Sairaanhoitajat työn imussa? Palkkatyön sisällön ja kulttuuristen lähtökohtien tasapainossa

Tutkimuksen tavoitteena on selvittää, mikä saa pitkän työuran tehneet sairaanhoitajat innostumaan työstään. Taustalla on yhteiskunnallinen tilanne, jossa työelämän vetovoimaisuuden lisääminen ja ikääntyvien työntekijöiden työssä jaksaminen ovat keskeisiä poliittisia tavoitteita. Aihetta lähestytään positiivisesta psykologiasta lähtöisin olevan työn imun käsitteen avulla. Se on määritelty pysyväksi, ”myönteiseksi, tunne- ja motivaatiotäyttymyksen tilaksi, jota luonnehtivat tarmokkuus, omistautuminen ja uppoutuminen työhön” (Hakanen 2009a, 9). Tutkimuksessa kysytään, voidaanko työn imua ymmärtää myös sosiologisesta näkökulmasta. Oletuksena on, että käsitteen taustalla on muutakin kuin psykologisesta perinteestä käsin jäsentyvää vaihtelua. Empiirisen aineiston muodostavan 11 sairaanhoitajan koko työuraa ja nykyistä työtä koskevat tiettyihin teemoihin ankkuroidut syvähaastattelut. Otosta poimittaessa on etsitty sellaisia haastateltavia, jotka kokevat kantavansa työn imua. Aineiston analyysitapana on käytetty matriisin avulla sovellettua kvalitatiivista sisällönanalyysiä. Työn imua hahmotetaan analyysissä henkilöhistoriallisten haastatteluiden – menneen, nykyisen ja tulevan – kautta. Pyrkimyksenä on etsiä tarinoita mahdollisesti yhdistävää kulttuurista muotoa ja ymmärtää, mihin se perustuu. Analyysin nojalla vastuurationaalisuuden käsite (esim. Korvajärvi 1986) näyttäisi jäsentävän osan haastateltavien suhteesta työhönsä. Avain työn imun löytymiseen näissä tarinoissa on kuitenkin se, kuinka haastateltavilla on ollut henkilökohtainen halu mennä eteenpäin ja kykyä ratkaista ongelmia työuransa aikana ja nykyisessä työssään. Tämä havainto tulkitaan Max Weberin (1922; 1980) käsitteiden – arvorationaalisen ja päämäärärationaalisen toiminnan väliseen suhteen – avulla. Tulokseksi syntyy oletus siitä, että analyysin kohteena olevissa tarinoissa on kyse yhteisestä kulttuurisesta tarinasta siitä, millainen on hyvä ihminen, miten hyvä ihminen toteuttaa itseään työssä ja miten hän tekee työtään: tarmokkaasti, omistautuen ja uppoutuen. Henkilökohtainen halu mennä eteenpäin ja kyky ratkaista ongelmia nojaa sairaanhoitajien erityiseen eetokseen, kutsumustyöhön ja hoivan moraaliin tavalla, joka on rakenteellisesti yhtäläinen protestanttisuutta leimaavan yksilöllisen jumalasuhteen kanssa. Lisäksi analyysin perusteella esitetään, että työn imun edellytys on arvorationaalisen eetoksen lisäksi oikeanlainen, riittävät työn voimavarat sisältävä ympäristö, jossa hoitotyön keskeiset palkinnot on mahdollista saavuttaa. Tällöin palkkatyön sisältö kohtaa kulttuuriset lähtökohdat, ja tulos näkyy työn imuna. Keskeisimmät taustoittavat lähteet ovat Henriksson, Lea & Wrede, Sirpa (toim.) (2004a). Hyvinvointityön ammatit ja Hakanen, Jari (2009a). Työn imun arviointimenetelmä (Utrecht Work Engagement Scale). Sosiologisen tulkinnan kannalta tärkein teoreettinen lähde on Weber, Max (1980): Protestanttinen etiikka ja kapitalismin henki.

Uutta, vanhaa ja lainattua : Tampereen Kaupunkilähetyksen kristillissosiaalisen työn asemoituminen hyvinvointivaltion rakentumisessa vuosina 1939−1973

The main purpose of this study was to provide a full account of the Christian social work carried out at the Tampere City Mission (TCM) as well as the Missions sphere of operations from the Second World War to the early 1970s, comprising a period of significant change. The study consists of charting the processes of change and connections within the activities of the TCM and how examining these were linked to the general tendencies of the period, in lay work, social work, professionalization and the representation of gender. The positioning of the activities is described on the basis of these tendencies. The main sources for the study were the archives of the Mission, for example the minutes of meetings, correspondences as well as annual reports, and the archives of its partners, such as the City of Tampere, the Evangelical Lutheran parishes of Tampere and the State Welfare Administration. The archives of the Helsinki, Turku and Stockholm Missions supplied comparison reference and other material. In particular, social welfare and Christian social work technical journals of were used as printed sources. The principal method used was the genetic method of historiology. The research subject was also evaluated from the point of view of third sector research in addition to that of professionalization studies and gender studies. By the beginning of the research period, the TCM had turned more and more dedicatedly into a multipurpose social service organization maintaining social services such as old people s homes and children´s homes. This development continued, even though new areas of activity emerged and older ones fell into disuse. Social innovations sprang up, marriage counseling being one of them. On the national level, the TCM pioneered the provision of sheltered industrial work for intellectually disabled persons as well as housing services for them. As new activities were initiated, they overlapped with the established ones, and the TCM handed some of its child protection functions over to the municipality, in accordance with the current adaptation theory. The use of its own property to produce ever-changing social services may be the reason why the association s work continued on with vitality. Functional networks and political aid in the field of social services also bolstered the association. As in other Nordic countries, nonprofit organizations served as partners rather than competitors, with the State establishing institutional welfare arrangements. In the 1960s the municipal takeover of social services impacted the TCM activities. Rules for government subsidies and municipal allowances were not well established; hence these funds were not easily available, making improvements difficult. The TCM was a community in which women had a relatively strong position and an opportunity to make a difference. Female staff were reasonably equal to men, and women worked as heads of a several institutions. Care work employed a number of men, which went against the traditional segregation of labour between the sexes. The TCM s operations were from early on very professionalized, and were developed with particular care. Keywords: Christian social work, third sector, professionalization, gender

Process Analytical Technology Approach on Fluid Bed Granulation and Drying : Identifying Critical Relationships and Constructing the Design Space

Fluid bed granulation is a key pharmaceutical process which improves many of the powder properties for tablet compression. Dry mixing, wetting and drying phases are included in the fluid bed granulation process. Granules of high quality can be obtained by understanding and controlling the critical process parameters by timely measurements. Physical process measurements and particle size data of a fluid bed granulator that are analysed in an integrated manner are included in process analytical technologies (PAT). Recent regulatory guidelines strongly encourage the pharmaceutical industry to apply scientific and risk management approaches to the development of a product and its manufacturing process. The aim of this study was to utilise PAT tools to increase the process understanding of fluid bed granulation and drying. Inlet air humidity levels and granulation liquid feed affect powder moisture during fluid bed granulation. Moisture influences on many process, granule and tablet qualities. The approach in this thesis was to identify sources of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilise the PAT and design space concepts for the fluid bed granulation and drying. Monitoring the material behaviour in a fluidised bed has traditionally relied on the observational ability and experience of an operator. There has been a lack of good criteria for characterising material behaviour during spraying and drying phases, even though the entire performance of a process and end product quality are dependent on it. The granules were produced in an instrumented bench-scale Glatt WSG5 fluid bed granulator. The effect of inlet air humidity and granulation liquid feed on the temperature measurements at different locations of a fluid bed granulator system were determined. This revealed dynamic changes in the measurements and enabled finding the most optimal sites for process control. The moisture originating from the granulation liquid and inlet air affected the temperature of the mass and pressure difference over granules. Moreover, the effects of inlet air humidity and granulation liquid feed rate on granule size were evaluated and compensatory techniques used to optimize particle size. Various end-point indication techniques of drying were compared. The ∆T method, which is based on thermodynamic principles, eliminated the effects of humidity variations and resulted in the most precise estimation of the drying end-point. The influence of fluidisation behaviour on drying end-point detection was determined. The feasibility of the ∆T method and thus the similarities of end-point moisture contents were found to be dependent on the variation in fluidisation between manufacturing batches. A novel parameter that describes behaviour of material in a fluid bed was developed. Flow rate of the process air and turbine fan speed were used to calculate this parameter and it was compared to the fluidisation behaviour and the particle size results. The design space process trajectories for smooth fluidisation based on the fluidisation parameters were determined. With this design space it is possible to avoid excessive fluidisation and improper fluidisation and bed collapse. Furthermore, various process phenomena and failure modes were observed with the in-line particle size analyser. Both rapid increase and a decrease in granule size could be monitored in a timely manner. The fluidisation parameter and the pressure difference over filters were also discovered to express particle size when the granules had been formed. The various physical parameters evaluated in this thesis give valuable information of fluid bed process performance and increase the process understanding.

Lebanese Plants and Plant-Derived Compounds Against Colon Cancer

Colorectal cancer (CRC) is a major health concern and demands long-term efforts in developing strategies for screening and prevention. CRC has become a preventable disease as a consequence of a better understanding of colorectal carcinogenesis. However, current therapy is unsatisfactory and necessitates the exploration of other approaches for the prevention and treatment of cancer. Plant based products have been recognized as preventive with regard to the development of colon cancer. Therefore, the potential chemopreventive use and mechanism of action of Lebanese natural product were evaluated. Towards this aim the antitumor activity of Onopordum cynarocephalum and Centaurea ainetensis has been studied using in vitro and in vivo models. In vitro, both crude extracts were non cytotoxic to normal intestinal cells and inhibited the proliferation of colon cancer cells in a dose-dependent manner. In vivo, both crude extracts reduced the number of tumors by an average of 65% at weeks 20 (adenomas stage) and 30 (adenocarcinomas stage). The activity of the C. ainetensis extract was attributed to Salograviolide A, a guaianolide-type sesquiterpene lactone, which was isolated and identified through bio-guided fractionation. The mechanism of action of thymoquinone (TQ), the active component of Nigella sativa, was established in colon cancer cells using in vitro models. By the use of N-acetyl cysteine, a radical scavenger, the direct involvement of reactive oxygen species in TQ-induced apoptotic cells was established. The analytical detection of TQ from spiked serum and its protein binding were evaluated. The average recovery of TQ from spiked serum subjected to several extraction procedures was 2.5% proving the inability of conventional methods to analyze TQ from serum. This has been explained by the extensive binding (>98%) of TQ to serum and major serum components such as bovine serum albumin (BSA) and alpha-1-acid glycoprotein (AGP). Using mass spectrometry analysis, TQ was confirmed to bind covalently to the free cysteine in position 34 and 147 of the amino acid sequence of BSA and AGP, respectively. The results of this work put at the disposal for future development new plants with anti-cancer activities and enhance the understanding of the pharmaceutical properties of TQ, a prerequisite for its future clinical development.

Thin-Layer Chromatography with Ultraviolet and Mass Spectrometric Detection: From Preparative-Layer to Miniaturized Ultra-Thin-Layer Technique

The present challenge in drug discovery is to synthesize new compounds efficiently in minimal time. The trend is towards carefully designed and well-characterized compound libraries because fast and effective synthesis methods easily produce thousands of new compounds. The need for rapid and reliable analysis methods is increased at the same time. Quality assessment, including the identification and purity tests, is highly important since false (negative or positive) results, for instance in tests of biological activity or determination of early-ADME parameters in vitro (the pharmacokinetic study of drug absorption, distribution, metabolism, and excretion), must be avoided. This thesis summarizes the principles of classical planar chromatographic separation combined with ultraviolet (UV) and mass spectrometric (MS) detection, and introduces powerful, rapid, easy, low-cost, and alternative tools and techniques for qualitative and quantitative analysis of small drug or drug-like molecules. High performance thin-layer chromatography (HPTLC) was introduced and evaluated for fast semi-quantitative assessment of the purity of synthesis target compounds. HPTLC methods were compared with the liquid chromatography (LC) methods. Electrospray ionization mass spectrometry (ESI MS) and atmospheric pressure matrix-assisted laser desorption/ionization MS (AP MALDI MS) were used to identify and confirm the product zones on the plate. AP MALDI MS was rapid, and easy to carry out directly on the plate without scraping. The PLC method was used to isolate target compounds from crude synthesized products and purify them for bioactivity and preliminary ADME tests. Ultra-thin-layer chromatography (UTLC) with AP MALDI MS and desorption electrospray ionization mass spectrometry (DESI MS) was introduced and studied for the first time. Because of the thinner adsorbent layer, the monolithic UTLC plate provided 10 100 times better sensitivity in MALDI analysis than did HPTLC plates. The limits of detection (LODs) down to low picomole range were demonstrated for UTLC AP MALDI and UTLC DESI MS. In a comparison of AP and vacuum MALDI MS detection for UTLC plates, desorption from the irregular surface of the plates with the combination of an external AP MALDI ion source and an ion trap instrument provided clearly less variation in mass accuracy than the vacuum MALDI time-of-flight (TOF) instrument. The performance of the two-dimensional (2D) UTLC separation with AP MALDI MS method was studied for the first time. The influence of the urine matrix on the separation and the repeatability was evaluated with benzodiazepines as model substances in human urine. The applicability of 2D UTLC AP MALDI MS was demonstrated in the detection of metabolites in an authentic urine sample.

Characterisation and processing of amorphous binary mixtures with low glass transition temperature

The number of drug substances in formulation development in the pharmaceutical industry is increasing. Some of these are amorphous drugs and have glass transition below ambient temperature, and thus they are usually difficult to formulate and handle. One reason for this is the reduced viscosity, related to the stickiness of the drug, that makes them complicated to handle in unit operations. Thus, the aim in this thesis was to develop a new processing method for a sticky amorphous model material. Furthermore, model materials were characterised before and after formulation, using several characterisation methods, to understand more precisely the prerequisites for physical stability of amorphous state against crystallisation. The model materials used were monoclinic paracetamol and citric acid anhydrate. Amorphous materials were prepared by melt quenching or by ethanol evaporation methods. The melt blends were found to have slightly higher viscosity than the ethanol evaporated materials. However, melt produced materials crystallised more easily upon consecutive shearing than ethanol evaporated materials. The only material that did not crystallise during shearing was a 50/50 (w/w, %) blend regardless of the preparation method and it was physically stable at least two years in dry conditions. Shearing at varying temperatures was established to measure the physical stability of amorphous materials in processing and storage conditions. The actual physical stability of the blends was better than the pure amorphous materials at ambient temperature. Molecular mobility was not related to the physical stability of the amorphous blends, observed as crystallisation. Molecular mobility of the 50/50 blend derived from a spectral linewidth as a function of temperature using solid state NMR correlated better with the molecular mobility derived from a rheometer than that of differential scanning calorimetry data. Based on the results obtained, the effect of molecular interactions, thermodynamic driving force and miscibility of the blends are discussed as the key factors to stabilise the blends. The stickiness was found to be affected glass transition and viscosity. Ultrasound extrusion and cutting were successfully tested to increase the processability of sticky material. Furthermore, it was found to be possible to process the physically stable 50/50 blend in a supercooled liquid state instead of a glassy state. The method was not found to accelerate the crystallisation. This may open up new possibilities to process amorphous materials that are otherwise impossible to manufacture into solid dosage forms.

Liquid Chromatography-Mass Spectrometry in Studies of Drug Metabolism and Permeability

Poor pharmacokinetics is one of the reasons for the withdrawal of drug candidates from clinical trials. There is an urgent need for investigating in vitro ADME (absorption, distribution, metabolism and excretion) properties and recognising unsuitable drug candidates as early as possible in the drug development process. Current throughput of in vitro ADME profiling is insufficient because effective new synthesis techniques, such as drug design in silico and combinatorial synthesis, have vastly increased the number of drug candidates. Assay technologies for larger sets of compounds than are currently feasible are critically needed. The first part of this work focused on the evaluation of cocktail strategy in studies of drug permeability and metabolic stability. N-in-one liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the multiple component analysis of samples in cocktail experiments. Together, cocktail dosing and LC/MS/MS were found to form an effective tool for increasing throughput. First, cocktail dosing, i.e. the use of a mixture of many test compounds, was applied in permeability experiments with Caco-2 cell culture, which is a widely used in vitro model for small intestinal absorption. A cocktail of 7-10 reference compounds was successfully evaluated for standardization and routine testing of the performance of Caco-2 cell cultures. Secondly, cocktail strategy was used in metabolic stability studies of drugs with UGT isoenzymes, which are one of the most important phase II drug metabolizing enzymes. The study confirmed that the determination of intrinsic clearance (Clint) as a cocktail of seven substrates is possible. The LC/MS/MS methods that were developed were fast and reliable for the quantitative analysis of a heterogenous set of drugs from Caco-2 permeability experiments and the set of glucuronides from in vitro stability experiments. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), was evaluated through comparison with electrospray ionization (ESI), where both techniques were used for the analysis of Caco-2 samples. Like ESI, also APPI proved to be a reliable technique for the analysis of Caco-2 samples and even more flexible than ESI because of the wider dynamic linear range. The second part of the experimental study focused on metabolite profiling. Different mass spectrometric instruments and commercially available software tools were investigated for profiling metabolites in urine and hepatocyte samples. All the instruments tested (triple quadrupole, quadrupole time-of-flight, ion trap) exhibited some good and some bad features in searching for and identifying of expected and non-expected metabolites. Although, current profiling software is helpful, it is still insufficient. Thus a time-consuming largely manual approach is still required for metabolite profiling from complex biological matrices.

The Phraseology and Structure of Latin Building Inscriptions in Roman North Africa

This study analyses the diction of Latin building inscriptions. Despite its importance, this topic has rarely been discussed before: the most substantial contribution on the subject is a short dissertation by Klaus Gast (1965) that focuses on 100 inscriptions dating mostly from the Republican period. Marietta Horster (2001) also touched upon this theme in her thesis on imperial building inscriptions. I have collected my source material in North Africa because more Latin building inscriptions dating from the Imperial period have survived there than in any other area of the Roman Empire. By means of a thorough and independent survey, I have assembled all relevant African Latin building inscriptions datable to the Roman period (between 146 BC and AD 425), 1002 texts, into a corpus. These inscriptions are all fully edited in Appendix 1; Appendix 2 contains references to earlier editions. To facilitate search operations, both are also available in electronic form. They are downloadable from the address http://www.helsinki.fi/hum/kla/htm/jatkoopinnot.htm. Chapter one is an introduction dealing with the nature of building inscriptions as source material. Chapter two offers a statistical overview of the material. The following main section of the work falls into five chapters, each of which analyses one main part of a building inscription. An average building inscription can be divided into five parts: the starting phrase opens the inscription (a dedication to gods, for example), the subject part identifies the builder, the object part describes the constructed or repaired building, the predicate part records the building activity and the supplement part offers additional information on the project (it can specify the funding, for instance). These chapters are systematic and chronological and their purpose is to register and interpret the phrases used, to analyse reasons for their use and for their popularity among the different groups of builders. Chapter eight, which follows the main section of the work, creates a typology of building inscriptions based on their structure. It also presents the most frequently attested types of building inscriptions. The conclusion describes, on a general level, how the diction of building inscriptions developed during the period of study and how this striking development resulted from socio-economic changes that took place in Romano-African society during Antiquity. This study shows that the phraseology of building inscriptions had a clear correlation both with the type of builder and with the date of carving. Private builders tended to accentuate their participation (especially its financial side) in the project; honouring the emperor received more emphasis in the building inscriptions set up by communities; the texts produced by the army were concise. The chronological development is so clear that it enables stylistic dating. At the beginning of the imperial period the phrases were clear, concrete, formal and stereotyped but by Late Antiquity they have become vague, subjective, flexible, varied and even rhetorically or poetically coloured.