31 resultados para ESI-FTICRMS

em Helda - Digital Repository of University of Helsinki


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Tutkielmassa tarkastellaan esi-isien merkitystä sukuma-nymawezi-alueen ennustajientyössä. Työ perustuu kenttätyömateriaaliin, joka on pääasiassa kerätty neljän kylän muodostamalta hallinnolliselta alueelta, Isakasta, joka sijaitsee sukuma-nyamwczi-alueen kes-kiosissa. Sukumat ja nyamwezit ovat Tansanian suurimmat kansat ja muodostavat kulttuurisesti hyvinkin yhtenäisen alueen. Isakan alue, jossa kenttätyö on tehty, on nopeasti kasvava keskus, jonka kasvun ovat mahdollistaneet erinomaiset liikenneyhteydet, joiden vaikutuksesta alueelle on muuttanut useiden kansojen edustajia lähinnä vaurastumisen toivossa. Mm. ennustajia alueella on runsaasti juuri tästä syystä. Tutkielmassa esitellään erilaisia näkökulmia ennustukseen ja esi-isien merkitykseen Isakassa. Ennustuksen asiantuntijoiden, ennustajien, lisäksi näitä näkökulmia tarjoavat alueen perinteisten tanssirituaalien johtajat sekä länsimaisen terveydenhuollon ja valtion kulttuuriviraston edustajat. Nämä eri tahot edustavat usein jopa vastakkaisia näkemyksiä ennustuksen merkitykseen yhteisössä. Tutkielmassa tarkastellaan kuitenkin sitä, miten nämä toisistaan poikkeavat näkemykset yhdistyvät yksilöiden (isakalaisten naisten) kohdalla erilaisiksi kokonaisuuksiksi, joissa erilaiset näkemykset täydentävät toisiaan. Isakassa ennustajat selvittävät erilaisten ennustusmenetelmien avulla asiakkaittensa ongelmat ja tarvittavat hoitomuodot. Ennustuksen lisäksi he tarjoavat usein asiakkailleen myöstarvittavan hoidon. Lähes poikkeuksetta ennustus tapahtuu esi-isien tai muiden henkienavulla. Ennustuksessa voidaan käyttää henkipossessiota, jolloin henki kertoo asiakkaanongelmat ennustajan ruumiin kautta. Myös käytettäessä muita ennustusmenetelmiä kuin henkipossessiota, on esi-isien merkitys suuri, sillä ennustajan kykyjen nähdään olevannäiltä peräisin. Tutkielmassa esi-isien ja mahdollisten muiden henkien merkitystä ennus-tustyössä valotetaan henkipossessioteorioiden avulla ja tarkastellaan mm. sitä, miten esi-isät kommentoivat yhteisön jäsenten elämää "historian äänenä". Sukuma-nyamwezi-kosmologiassa esi-isät ja noituus nähdään mahdollisina sairauksien j amuiden ongelmien aiheuttajina. Erityisesti näissä tapauksissa virallisen (länsimaisen) terveydenhuollon palveluja ei nähdä riittävinä. Tutkielmassa korostetaankin sitä, miten isakalaisille ennustajien ja virallisen terveydenhuollon palvelut näyttäytyvät toisiaan täydentävi-nä vaihtoehtoina etsittäessä ratkaisuja sairauksien tai muiden ongelmien alkuperään ja tar-vittavaan hoitoon. Avainsanat: Tansania; sukuma-nyamwczi; ennustus; esi-isät ja muut henget; noituus

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Tämän itsenäisistä osatutkimuksista koostuvan tutkimussarjan tavoitteena oli pyrkiä täydentämään kuvaa matemaattisilta taidoiltaan heikkojen lasten ja nuorten tiedonkäsittelyvalmiuksista selvittämällä, ovatko visuaalis-spatiaaliset työmuistivalmiudet yhteydessä matemaattiseen suoriutumiseen. Teoreettinen viitekehys rakentui Baddeleyn (1986, 1997) kolmikomponenttimallin ympärille. Työmuistikäsitys oli kuitenkin esikuvaansa laajempi sisällyttäen visuaalis-spatiaaliseen työmuistiin Cornoldin ja Vecchin (2003) termein sekä passiiviset varastotoiminnot että aktiiviset prosessointitoiminnot. Yhteyksiä työmuistin ja matemaattisten taitojen välillä tarkasteltiin viiden eri osatutkimuksen avulla. Kaksi ensimmäistä keskittyivät alle kouluikäisten lukukäsitteen hallinnan ja visuaalis-spatiaalisten työmuistivalmiuksen tutkimiseen ja kolme jälkimmäistä peruskoulun yhdeksäsluokkalaisten matemaattisten taitojen ja visuaalis-spatiaalisten työmuistitaitojen välisten yhteyksien selvittämiseen. Tutkimussarjan avulla pyrittiin selvittämään, ovatko visuaalis-spatiaaliset työmuistivalmiudet yhteydessä matemaattiseen suoriutumiseen sekä esi- että yläkouluiässä (osatutkimukset I, II, III, IV, V), onko yhteys spesifi rajoittuen tiettyjen visuaalis-spatiaalisten valmiuksien ja matemaattisen suoriutumisen välille vai onko se yleinen koskien matemaattisia taitoja ja koko visuaalis-spatiaalista työmuistia (osatutkimukset I, II, III, IV, V) tai työmuistia laajemmin (osatutkimukset II, III) sekä onko yhteys työmuistispesifi vai selitettävissä älykkyyden kaltaisella yleisellä päättelykapasiteetilla (osatutkimukset I, II, IV). Tutkimussarjan tulokset osoittavat, että kyky säilyttää ja käsitellä hetkellisesti visuaalis-spatiaalista informaatiota on yhteydessä matemaattiseen suoriutumiseen eikä yhteyttä voida selittää yksinomaan joustavalla älykkyydellä. Suoriutuminen visuaalis-spatiaalista työmuistia mittaavissa tehtävissä on yhteydessä sekä alle kouluikäisten esimatemaattisten taitojen hallintaan että peruskoulun yhdeksäsluokkalaisten matematiikan taitoihin. Matemaattisilta taidoiltaan heikkojen lasten ja nuorten visuaalis-spatiaalisten työmuistiresurssien heikkoudet vaikuttavat kuitenkin olevan sangen spesifejä rajoittuen tietyntyyppisissä muistitehtävissä vaadittaviin valmiuksiin; kaikissa visuaalis-spatiaalisen työmuistin valmiuksia mittaavissa tehtävissä suoriutuminen ei ole yhteydessä matemaattisiin taitoihin. Työmuistivalmiuksissa ilmenevät erot sekä alle kouluikäisten että kouluikäisten matemaattisilta taidoiltaan heikkojen ja normaalisuoriutujien välillä näyttävät olevan kuitenkin jossain määrin yhteydessä kielellisiin taitoihin viitaten vaikeuksien tietynlaiseen kasautumiseen; niillä matemaattisesti heikoilla, joilla on myös kielellisiä vaikeuksia, on keskimäärin laajemmat työmuistiheikkoudet. Osalla matematiikassa heikosti suoriutuvista on näin ollen selvästi keskimääräistä heikommat visuaalis-spatiaaliset työmuistivalmiudet, ja tämä heikkous saattaa olla yksi mahdollinen syy tai vaikeuksia lisäävä tekijä heikon matemaattisen suoriutumisen taustalla. Visuaalis-spatiaalisen työmuistin heikkous merkitsee konkreettisesti vähemmän mentaalista prosessointitilaa, joka rajoittaa oppimista ja suoritustilanteita. Tiedonkäsittelyvalmiuksien heikkous liittyy nimenomaan oppimisnopeuteen, ei asioiden opittavuuteen sinänsä. Mikäli oppimisympäristö ottaa huomioon valmiuksien rajallisuuden, työmuistiheikkoudet eivät todennäköisesti estä asioiden oppimista sinänsä. Avainsanat: Työmuisti, visuaalis-spatiaalinen työmuisti, matemaattiset taidot, lukukäsite, matematiikan oppimisvaikeudet

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Miniaturization of analytical instrumentation is attracting growing interest in response to the explosive demand for rapid, yet sensitive analytical methods and low-cost, highly automated instruments for pharmaceutical and bioanalyses and environmental monitoring. Microfabrication technology in particular, has enabled fabrication of low-cost microdevices with a high degree of integrated functions, such as sample preparation, chemical reaction, separation, and detection, on a single microchip. These miniaturized total chemical analysis systems (microTAS or lab-on-a-chip) can also be arrayed for parallel analyses in order to accelerate the sample throughput. Other motivations include reduced sample consumption and waste production as well as increased speed of analysis. One of the most promising hyphenated techniques in analytical chemistry is the combination of a microfluidic separation chip and mass spectrometer (MS). In this work, the emerging polymer microfabrication techniques, ultraviolet lithography in particular, were exploited to develop a capillary electrophoresis (CE) separation chip which incorporates a monolithically integrated electrospray ionization (ESI) emitter for efficient coupling with MS. An epoxy photoresist SU-8 was adopted as structural material and characterized with respect to its physicochemical properties relevant to chip-based CE and ESI/MS, namely surface charge, surface interactions, heat transfer, and solvent compatibility. As a result, SU-8 was found to be a favorable material to substitute for the more commonly used glass and silicon in microfluidic applications. In addition, an infrared (IR) thermography was introduced as direct, non-intrusive method to examine the heat transfer and thermal gradients during microchip-CE. The IR data was validated through numerical modeling. The analytical performance of SU-8-based microchips was established for qualitative and quantitative CE-ESI/MS analysis of small drug compounds, peptides, and proteins. The CE separation efficiency was found to be similar to that of commercial glass microchips and conventional CE systems. Typical analysis times were only 30-90 s per sample indicating feasibility for high-throughput analysis. Moreover, a mass detection limit at the low-attomole level, as low as 10E+5 molecules, was achieved utilizing MS detection. The SU-8 microchips developed in this work could also be mass produced at low cost and with nearly identical performance from chip to chip. Until this work, the attempts to combine CE separation with ESI in a chip-based system, amenable to batch fabrication and capable of high, reproducible analytical performance, have not been successful. Thus, the CE-ESI chip developed in this work is a substantial step toward lab-on-a-chip technology.

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The feasibility of different modern analytical techniques for the mass spectrometric detection of anabolic androgenic steroids (AAS) in human urine was examined in order to enhance the prevalent analytics and to find reasonable strategies for effective sports drug testing. A comparative study of the sensitivity and specificity between gas chromatography (GC) combined with low (LRMS) and high resolution mass spectrometry (HRMS) in screening of AAS was carried out with four metabolites of methandienone. Measurements were done in selected ion monitoring mode with HRMS using a mass resolution of 5000. With HRMS the detection limits were considerably lower than with LRMS, enabling detection of steroids at low 0.2-0.5 ng/ml levels. However, also with HRMS, the biological background hampered the detection of some steroids. The applicability of liquid-phase microextraction (LPME) was studied with metabolites of fluoxymesterone, 4-chlorodehydromethyltestosterone, stanozolol and danazol. Factors affecting the extraction process were studied and a novel LPME method with in-fiber silylation was developed and validated for GC/MS analysis of the danazol metabolite. The method allowed precise, selective and sensitive analysis of the metabolite and enabled simultaneous filtration, extraction, enrichment and derivatization of the analyte from urine without any other steps in sample preparation. Liquid chromatographic/tandem mass spectrometric (LC/MS/MS) methods utilizing electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) were developed and applied for detection of oxandrolone and metabolites of stanozolol and 4-chlorodehydromethyltestosterone in urine. All methods exhibited high sensitivity and specificity. ESI showed, however, the best applicability, and a LC/ESI-MS/MS method for routine screening of nine 17-alkyl-substituted AAS was thus developed enabling fast and precise measurement of all analytes with detection limits below 2 ng/ml. The potential of chemometrics to resolve complex GC/MS data was demonstrated with samples prepared for AAS screening. Acquired full scan spectral data (m/z 40-700) were processed by the OSCAR algorithm (Optimization by Stepwise Constraints of Alternating Regression). The deconvolution process was able to dig out from a GC/MS run more than the double number of components as compared with the number of visible chromatographic peaks. Severely overlapping components, as well as components hidden in the chromatographic background could be isolated successfully. All studied techniques proved to be useful analytical tools to improve detection of AAS in urine. Superiority of different procedures is, however, compound-dependent and different techniques complement each other.

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Miniaturized analytical devices, such as heated nebulizer (HN) microchips studied in this work, are of increasing interest owing to benefits like faster operation, better performance, and lower cost relative to conventional systems. HN microchips are microfabricated devices that vaporize liquid and mix it with gas. They are used with low liquid flow rates, typically a few µL/min, and have previously been utilized as ion sources for mass spectrometry (MS). Conventional ion sources are seldom feasible at such low flow rates. In this work HN chips were developed further and new applications were introduced. First, a new method for thermal and fluidic characterization of the HN microchips was developed and used to study the chips. Thermal behavior of the chips was also studied by temperature measurements and infrared imaging. An HN chip was applied to the analysis of crude oil – an extremely complex sample – by microchip atmospheric pressure photoionization (APPI) high resolution mass spectrometry. With the chip, the sample flow rate could be reduced significantly without loss of performance and with greatly reduced contamination of the MS instrument. Thanks to its suitability to high temperature, microchip APPI provided efficient vaporization of nonvolatile compounds in crude oil. The first microchip version of sonic spray ionization (SSI) was presented. Ionization was achieved by applying only high (sonic) speed nebulizer gas to an HN microchip. SSI significantly broadens the range of analytes ionizable with the HN chips, from small stable molecules to labile biomolecules. The analytical performance of the microchip SSI source was confirmed to be acceptable. The HN microchips were also used to connect gas chromatography (GC) and capillary liquid chromatography (LC) to MS, using APPI for ionization. Microchip APPI allows efficient ionization of both polar and nonpolar compounds whereas with the most popular electrospray ionization (ESI) only polar and ionic molecules are ionized efficiently. The combination of GC with MS showed that, with HN microchips, GCs can easily be used with MS instruments designed for LC-MS. The presented analytical methods showed good performance. The first integrated LC–HN microchip was developed and presented. In a single microdevice, there were structures for a packed LC column and a heated nebulizer. Nonpolar and polar analytes were efficiently ionized by APPI. Ionization of nonpolar and polar analytes is not possible with previously presented chips for LC–MS since they rely on ESI. Preliminary quantitative performance of the new chip was evaluated and the chip was also demonstrated with optical detection. A new ambient ionization technique for mass spectrometry, desorption atmospheric pressure photoionization (DAPPI), was presented. The DAPPI technique is based on an HN microchip providing desorption of analytes from a surface. Photons from a photoionization lamp ionize the analytes via gas-phase chemical reactions, and the ions are directed into an MS. Rapid analysis of pharmaceuticals from tablets was successfully demonstrated as an application of DAPPI.

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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.

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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.

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This doctoral dissertation examines the description of the North as it appears in the Old English Orosius (OE Or.) in the form of the travel accounts by Ohthere and Wulfstan and a catalogue of peoples of Germania. The description is discussed in the context of ancient and early medieval textual and cartographic descriptions of the North, with a special emphasis on Anglo-Saxon sources and the intellectual context of the reign of King Alfred (871-899). This is the first time that these sources, a multidisciplinary approach and secondary literature, also from Scandinavia and Finland, have been brought together. The discussion is source-based, and archaeological theories and geographical ideas are used to support the primary evidence. This study belongs to the disciplines of early medieval literature and (cultural) history, Anglo-Saxon studies, English philology, and historical geography. The OE Or. was probably part of Alfred s educational campaign, which conveyed royal ideology to the contemporary elite. The accounts and catalogue are original interpolations which represent a unique historical source for the Viking Age. They contain unparalleled information about peoples and places in Fennoscandia and the southern Baltic and sailing voyages to the White Sea, the Danish lands, and the Lower Vistula. The historical-philological analysis reveals an emphasis on wealth and property, rank, luxury goods, settlement patterns, and territorial divisions. Trade is strongly implied by the mentions of central places and northern products, such as walrus ivory. The references to such peoples as the Finnas, the Cwenas, and the Beormas appear in connection with information about geography and subsistence in the far North. Many of the topics in the accounts relate to Anglo-Saxon aristocratic culture and interests. The accounts focus on the areas associated with the Northmen, the Danes and the Este. These areas resonated in the Anglo-Saxon geographical imagination: they were curious about the northern margin of the world, their own continental ancestry and the geography of their homeland of Angeln, and they had an interest in the Goths and their connection with the southern Baltic in mythogeography. The non-judgemental representation of the North as generally peaceful and relatively normal place is related to Alfredian and Orosian ideas about the unity and spreading of Christendom, and to desires for unity among the Germani and for peace with the Vikings, who were settling in England. These intellectual contexts reflect the innovative and organizational forces of Alfred s reign. The description of the North in the OE Or. can be located in the context of the Anglo-Saxon worldview and geographical mindset. It mirrors the geographical curiosity expressed in other Anglo-Saxon sources, such as the poem Widsith and the Anglo-Saxon mappa mundi. The northern section of this early eleventh-century world map is analyzed in detail here for the first time. It is suggested that the section depicts the North Atlantic and the Scandinavian Peninsula. The survey of ancient and early medieval sources provides a comparative context for the OE Or. In this material, produced by such authors as Strabo, Pliny, Tacitus, Jordanes, and Rimbert, the significance of the North was related to the search for and definition of the northern edge of the world, universal accounts of the world, the northern homeland in the origin stories of the gentes, and Carolingian expansion and missionary activity. These frameworks were transmitted to Anglo-Saxon literary culture, where the North occurs in the context of the definition of Britain s place in the world.

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This study sets out to provide new information about the interaction between abstract religious ideas and actual acts of violence in the early crusading movement. The sources are asked, whether such a concept as religious violence can be sorted out as an independent or distinguishable source of aggression at the moment of actual bloodshed. The analysis concentrates on the practitioners of sacred violence, crusaders and their mental processing of the use of violence, the concept of the violent act, and the set of values and attitudes defining this concept. The scope of the study, the early crusade movement, covers the period from late 1080 s to the crusader conquest of Jerusalem in 15 July 1099. The research has been carried out by contextual reading of relevant sources. Eyewitness reports will be compared with texts that were produced by ecclesiastics in Europe. Critical reading of the texts reveals both connecting ideas and interesting differences between them. The sources share a positive attitude towards crusading, and have principally been written to propagate the crusade institution and find new recruits. The emphasis of the study is on the interpretation of images: the sources are not asked what really happened in chronological order, but what the crusader understanding of the reality was like. Fictional material can be even more crucial for the understanding of the crusading mentality. Crusader sources from around the turn of the twelfth century accept violent encounters with non-Christians on the grounds of external hostility directed towards the Christian community. The enemies of Christendom can be identified with either non-Christians living outside the Christian society (Muslims), non-Christians living within the Christian society (Jews) or Christian heretics. Western Christians are described as both victims and avengers of the surrounding forces of diabolical evil. Although the ideal of universal Christianity and gradual eradication of the non-Christian is present, the practical means of achieving a united Christendom are not discussed. The objective of crusader violence was thus entirely Christian: the punishment of the wicked and the restoration of Christian morals and the divine order. Meanwhile, the means used to achieve these objectives were not. Given the scarcity of written regulations concerning the use of force in bello, perceptions concerning the practical use of violence were drawn from a multitude of notions comprising an adaptable network of secular and ecclesiastical, pre-Christian and Christian traditions. Though essentially ideological and often religious in character, the early crusader concept of the practise of violence was not exclusively rooted in Christian thought. The main conclusion of the study is that there existed a definable crusader ideology of the use of force by 1100. The crusader image of violence involved several levels of thought. Predominantly, violence indicates a means of achieving higher spiritual rewards; eternal salvation and immortal glory.

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The thesis is connected with death, memory and ancestor commemoration during the Merovingian Period, the Viking Age and the beginning of the Crusade Period (AD 550-1150) in Finland. During this time, cremation was the dominant burial rite. It was not until the end of the Viking Age that inhumation became more common but both cremations and inhumations are performed even at the same sites throughout the time. Three different burial types 1) cremation cemeteries below level ground, 2) inhumation burials and 3) water burials are discussed in five articles. I consider these burial forms from three different viewpoints; collectivity-individuality, visibility-invisibility and cremation-inhumation. The thesis also discusses the topics of memory, memorialisation and monument re-use, which have been neglected subjects in Finnish archaeology until now. Both cremation cemeteries below level ground and inhumation burials have been re-used during their time of usage, and on most occasions are situated in a landscape that is overlaid by other monuments as well. The main questions of the thesis are: What kinds of ritual behaviour can we detect in the burials during the period (AD 550-1150)? How did people perceive the moraine hills that functioned as burial places? What kind of re-use can be detected in the Iron Age cemeteries? Why have ancient sites and artefacts been re-used? This thesis shows that it is possible to claim that both artefact and site re-use is a much more widespread phenomenon than has previously been thought in Finnish archaeology. It is also a conscious and deliberate behaviour that can be related to an ancestor cult and commemoration of the dead. The funerary rituals during this time period show great variation and complex, both regionally and nationally. Not only have the dead been buried using elaborate rituals, they have also been mourned and commemorated in intricate ways that proves that death was not an end product, but the start of something new.

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Epistemological foundationalism has for centuries attempted to unify all scientific inquiry into the context of one grand science, the first philosophy. One of the most important tasks of this tradition has been to ground all knowledge on absolutely certain foundations. In this master s thesis I ask the following question: To what extent and under what conditions is it possible to achieve absolute certainty in the sense of the attempts of Cartesian foundationalism? By examining how the 20th century philosophers, Edmund Husserl (1859-1938), Hannah Arendt (1906-1975) and Maurice Merleau-Ponty (1908-1961) interpret the epistemological methodology of René Descartes, I claim that the Cartesian achievement of absolute certainty rests on the implicit presupposition of an epistemologically prior form of faith in the world and trust (pistis) in other conscious beings. I show that knowledge is possible only within the context of a common world that is inhabited by several conscious beings that share a common linguistic system. This threefold element is shown to be the bedrock condition for any kind of philosophical inquiry. The main literature sources for this thesis are The Life of the Mind by Hannah Arendt, Le Visible et l invisible by Maurice Merleau-Ponty, Meditationes de Prima Philosophiae by René Descartes and Erfahrung und Urteil by Edmund Husserl.

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Tutkielmani käsittelee yhdysvaltalaisen kirjailijan Paul Austerin (s. 1947) romaanituotannossa esiintyviä esteitä ja rajatiloja. Erityisesti olen kiinnostunut siitä, miten Auster liittää nämä "marginaalitilat" amerikkalaiseen vapauden ja laajentumisen ideologiaan sekä kieleen ja kirjoittamiseen. Austerin romaaneissa esteiden ja rajatilojen käsittely voidaan jakaa kolmeen vaiheeseen. Ensimmäisessä vaiheessa henkilöt ovat vahvojen esteiden rajoittamia tai rakentavat niitä itse. Rajoittuneisuus ei kuitenkaan aina tunnu häiritsevän heitä - itse asiassa monet päähenkilöistä tuntevat itsensä onnellisiksi tai vähintäänkin tyytyväisiksi joutuessaan esteen takia pysähdyttämään vapaan liikkeensä. Toisessa vaiheessa henkilöt pyrkivät ylittämään tai rikkomaan esteen päästäkseen toiselle puolelle. Kuten amerikkalaiset esi-isänsä aikoinaan, he etsivät rajatonta, laajaa ja tyhjää tilaa - "suurta tuntematonta" valloitettavakseen. Tällaisen tilan kohdatessaan he joutuvat kuitenkin usein epävarmuuden valtaan. Kolmas vaihe on tutkielmani kannalta tärkein: välitila, josta käytän työssäni nimitystä "in-betweenity". Tähän vaiheeseen päästään kulkemalla ensin kahden muun vaiheen kautta. Juuri tietoisuus näistä kahdesta muusta vaiheesta synnyttää tämän kolmannen tilan, eräänlaisen rajatilan, jossa tajutaan sekä esteiden että esteettömyyden tärkeys. Tämä välitila on Austerille tyypillinen tila, joka kertoo paitsi amerikkalaisen unelman paradoksaalisuudesta myös (kaunokirjallisen) kielenkäytön prosessista. Monet Austerin kirjojen muurin rakentajista tai purkajista voidaan nähdä kirjailijahahmoina, joiden omituinen suhde esteisiin ja rajoihin kumpuaa juuri siitä rajatilasta, jonka asukkaita he kielentaiteilijoina väistämättä ovat. Tällaisen tilan/tilattomuuden kuvaaminen tekee Austerista oman postmodernin aikamme tärkeän kirjailijan - kirjailijan, joka sen sijaan, että pyrkisi eroon paradokseista, sijoittaa hahmonsa niiden sisään. Rajoihin ja esteisiin liittyvä problematiikka ei kuitenkaan ole pelkästään nykyajan ongelma vaan kysymys, joka ihmisen toisaalta rajoja kaipaavan toisaalta rajattomuutta kaipaavan luonteen vuoksi säilyy aina ajankohtaisena. Avainsanat: Paul Auster, este, muuri, raja, Yhdysvallat

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The purpose of this follow-up study is to analyse stages of learning and teaching of children with special needs in pre-school and the first two grades of elementary school. The target group included 270 children with special needs. The three year follow-up period for each child began during the pre-school year, and continued until the spring of the second grade in elementary school. Various diagnoses were detected among children in the study group. The disorders were categorised in six classes: the developmentally delayed, children with language development disorder, children with emotional and behavioural disorders, children with attention deficit, children with other non-cognitive disorders and children with extensive developmental disorders. The study's starting point was the situation in pre-school: how the children were placed in pre-school, and what kinds of support they were offered? The purpose of the study was to describe how children with special needs move from different types of groups in pre-school to the different types of classes in the first two grades of elementary school. I also examined how well the children with special needs succeeded in the first two grades of elementary school. An additional purpose was to find out what connections there may be between the paths taken by children with special needs when they move from pre-school to elementary school, the types of support they get, and how they succeed academically in elementary school. The data were gathered mainly by means of questionnaires. In addition the children were studied by means of tests designed to estimate their academic skills at the end of the second grade. In analysing the data I used both quantitative and qualitative methods. Six paths were identified among the children in the study group, based on whether a child was in a group or a class given special teaching or in an ordinary group or class during pre-school and the first two grades of elementary school. In this study, about 53% of the children with special needs moved from pre-school to a regular class in elementary school, and about 47% of the children received special education in elementary school. Among the ordinary groups (n = 69) in pre-school the majority of children (73 %) moved to a regular class in elementary school. Among the children receiving special education (n = 201) in pre-school, 46% moved to a regular class in elementary school. That path turned out to be the one followed by the greatest number of children. Only rarely did children move from an ordinary group in pre-school to a special education class in elementary school. Examination of the results according to the children's transition paths also links together with the viewpoint of integration and segregation. This study indicates that in pre-school special education groups, a significantly greater number of methods supporting children's development were used than in the conventional education groups. The difference was at its greatest inconnection with the use of so-called special rehabilitation methods. A quite wide range of variation was observed in how the children succeeded in elementary school. Success in the tests designed to estimate the children's academic skills was poor for 31% of the children (n = 230) in the first grade study group. For 69 % of the children, however, success in the tests was at least satisfactory. In the second grade study group 34 % of the children (N = 216) got through all the three tests estimating academic skills acceptably. According to this study, a number of children with special needs require special support throughout pre-school and the first two grades of elementary school. The results show that if the children received special support during the pre-school year, a number were able to participate in regular education in elementary school. Keywords: a child with special needs, measures of support, transitions, achievements in school

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We report here the structures and properties of heat-stable, non-protein, and mammalian cell-toxic compounds produced by spore-forming bacilli isolated from indoor air of buildings and from food. Little information is available on the effects and occurrence of heat-stable non-protein toxins produced by bacilli in moisture-damaged buildings. Bacilli emit spores that move in the air and can serve as the carriers of toxins, in a manner similar to that of the spores of toxic fungi found in contaminated indoor air. Bacillus spores in food cause problems because they tolerate the temperatures applied in food manufacture and the spores later initiate growth when food storage conditions are more favorable. Detection of the toxic compounds in Bacillus is based on using the change in mobility of boar spermatozoa as an indicator of toxic exposure. GC, LC, MS, and nuclear magnetic resonance NMR spectroscopy were used for purification, detection, quantitation, and analysis of the properties and structures of the compounds. Toxicity and the mechanisms of toxicity of the compounds were studied using boar spermatozoa, feline lung cells, human neural cells, and mitochondria isolated from rat liver. The ionophoric properties were studied using the BLM (black-lipid membrane) method. One novel toxin, forming ion channels permeant to K+ > Na+ > Ca2+, was found and named amylosin. It is produced by B. amyloliquefaciens isolated from indoor air of moisture-damaged buildings. Amylosin was purified with an RP-HPLC and a monoisotopic mass of 1197 Da was determined with ESI-IT-MS. Furthermore, acid hydrolysis of amylosin followed by analysis of the amino acids with the GS-MS showed that it was a peptide. The presence of a chromophoric polyene group was found using a NMR spectroscopy. The quantification method developed for amylosin based on RP-HPLC-UV, using the macrolactone polyene, amphotericin B (MW 924), as a reference compound. The B. licheniformis strains isolated from a food poisoning case produced a lipopeptide, lichenysin A, that ruptured mammalian cell membranes and was purified with a LC. Lichenysin A was identified by its protonated molecules and sodium- and potassium- cationized molecules with MALDI-TOF-MS. Its protonated forms were observed at m/z 1007, 1021 and 1035. The amino acids of lichenysin A were analyzed with ESI-TQ-MS/MS and, after acid hydrolysis, the stereoisomeric forms of the amino acids with RP-HPLC. The indoor air isolates of the strain of B. amyloliquefaciens produced not only amylosin but also lipopeptides: the cell membrane-damaging surfactin and the fungicidal fengycin. They were identified with ESI-IT-MS observing their protonated molecules, the sodium- and potassium-cationized molecules and analysing the MS/MS spectra. The protonated molecules of surfactin and fengycin showed m/z values of 1009, 1023, and 1037 and 1450, 1463, 1493, and 1506, respectively. Cereulide (MW 1152) was purified with RP-HPLC from a food poisoning strain of B. cereus. Cereulide was identified with ESI-TQ-MS according to the protonated molecule observed at m/z 1154 and the ammonium-, sodium- and potassium-cationized molecules observed at m/z 1171, 1176, and 1192, respectively. The fragment ions of the MS/MS spectrum obtained from the protonated molecule of cereulide at m/z 1154 were also interpreted. We developed a quantification method for cereulide, using RP-HPLC-UV and valinomycin (MW 1110, which structurally resembles cereulide) as the reference compound. Furthermore, we showed empirically, using the BLM method, that the emetic toxin cereulide is a specific and effective potassium ionophore of whose toxicity target is especially the mitochondria.

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When genome sections of wild Solanum species are bred into the cultivated potato (S. tuberosum L.) to obtain improved potato cultivars, the new cultivars must be evaluated for their beneficial and undesirable traits. Glycoalkaloids present in Solanum species are known for their toxic as well as for beneficial effects on mammals. On the other hand, glycoalkaloids in potato leaves provide natural protection against pests. Due to breeding, glycoalkaloid profile of the plant is affected. In addition, the starch properties in potato tubers can be affected as a result of breeding, because the crystalline properties are determined by the botanical source of the starch. Starch content and composition affect the texture of cooked and processed potatoes. In order to determine glycoalkaloid contents in Solanum species, simultaneous separation of glycoalkaloids and aglycones using reversed-phase high-performance liquid chromatography (HPLC) was developed. Clean-up of foliage samples was improved using a silica-based strong cation exchanger instead of octadecyl phases in solid-phase extraction. Glycoalkaloids alpha-solanine and alpha-chaconine were detected in potato tubers of cvs. Satu and Sini. The total glycoalkaloid concentration of non-peeled and immature tubers was at an acceptable level (under 20 mg/100 g of FW) in the cv. Satu, whereas concentration in cv. Sini was 23 mg/100 g FW. Solanum species (S. tuberosum, S. brevidens, S. acaule, and S. commersonii) and interspecific somatic hybrids (brd + tbr, acl + tbr, cmm + tbr) were analyzed for their glycoalkaloid contents using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The concentrations in the tubers of the brd + tbr and acl + tbr hybrids remained under 20 mg/100 g FW. Glycoalkaloid concentration in the foliage of the Solanum species was between 110 mg and 890 mg/100 g FW. However, the concentration in the foliage of S. acaule was as low as 26 mg/100 g FW. The total concentrations of brd + tbr, acl + tbr, and cmm + tbr hybrid foliages were 88 mg, 180 mg, and 685 mg/100 g FW, respectively. Glycoalkaloids of both parental plants as well as new combinations of aglycones and saccharides were detected in somatic hybrids. The hybrids contained mainly spirosolanes, and glycoalkaloid structures having no 5,6-double bond in the aglycone. Based on these results, the glycoalkaloid profiles of the hybrids may represent a safer and more beneficial spectrum of glycoalkaloids than that found in currently cultivated varieties. Starch nanostructure of three different cultivars (Satu, Saturna, and Lady Rosetta), a wild species S. acaule, and interspecific somatic hybrids were examined by wide-angle and small-angle X-ray scattering (WAXS, SAXS). For the first time, the measurements were conducted on fresh potato tuber samples. Crystallinity of starch, average crystallite size, and lamellar distance were determined from the X-ray patterns. No differences in the starch nanostructure between the three different cultivars were detected. However, tuber immaturity was detected by X-ray scattering methods when large numbers of immature and mature samples were measured and the results were compared. The present study shows that no significant changes occurred in the nanostructures of starches resulting from hybridizations of potato cultivars.