Roles of forced nicotine exposure and Comt gene disruption in the development of addiction-related behavioural and neurochemical changes in mice

Activation of midbrain dopamine systems is thought to be critically involved in the addictive properties of abused substances. Drugs of abuse increase dopamine release in the nucleus accumbens and dorsal striatum, which are the target areas of mesolimbic and nigrostriatal dopamine pathways, respectively. Dopamine release in the nucleus accumbens is thought to mediate the attribution of incentive salience to rewards, and dorsal striatal dopamine release is involved in habit formation. In addition, changes in the function of prefrontal cortex (PFC), the target area of mesocortical dopamine pathway, may skew information processing and memory formation such that the addict pays an abnormal amount of attention to drug-related cues. In this study, we wanted to explore how long-term forced oral nicotine exposure or the lack of catechol-O-methyltransferase (COMT), one of the dopamine metabolizing enzymes, would affect the functioning of these pathways. We also wanted to find out how the forced nicotine exposure or the lack of COMT would affect the consumption of nicotine, alcohol, or cocaine. First, we studied the effect of forced chronic nicotine exposure on the sensitivity of dopamine D2-like autoreceptors in microdialysis and locomotor activity experiments. We found that the sensitivity of these receptors was unchanged after forced oral nicotine exposure, although an increase in the sensitivity was observed in mice treated with intermittent nicotine injections twice daily for 10 days. Thus, the effect of nicotine treatment on dopamine autoreceptor sensitivity depends on the route, frequency, and time course of drug administration. Second, we investigated whether the forced oral nicotine exposure would affect the reinforcing properties of nicotine injections. The chronic nicotine exposure did not significantly affect the development of conditioned place preference to nicotine. In the intravenous self-administration paradigm, however, the nicotine-exposed animals self-administered nicotine at a lower unit dose than the control animals, indicating that their sensitivity to the reinforcing effects of nicotine was enhanced. Next, we wanted to study whether the Comt gene knock-out animals would be a suitable model to study alcohol and cocaine consumption or addiction. Although previous work had shown male Comt knock-out mice to be less sensitive to the locomotor-activating effects of cocaine, the present study found that the lack of COMT did not affect the consumption of cocaine solutions or the development of cocaine-induced place preference. However, the present work did find that male Comt knock-out mice, but not female knock-out mice, consumed ethanol more avidly than their wild-type littermates. This finding suggests that COMT may be one of the factors, albeit not a primary one, contributing to the risk of alcoholism. Last, we explored the effect of COMT deficiency on dorsal striatal, accumbal, and prefrontal cortical dopamine metabolism under no-net-flux conditions and under levodopa load in freely-moving mice. The lack of COMT did not affect the extracellular dopamine concentrations under baseline conditions in any of the brain areas studied. In the prefrontal cortex, the dopamine levels remained high for a prolonged time after levodopa treatment in male, but not female, Comt knock-out mice. COMT deficiency induced accumulation of 3,4-dihydroxyphenylacetic acid, which increased further under levodopa load. Homovanillic acid was not detectable in Comt knock-out animals either under baseline conditions or after levodopa treatment. Taken together, the present results show that although forced chronic oral nicotine exposure affects the reinforcing properties of self-administered nicotine, it is not an addiction model itself. COMT seems to play a minor role in dopamine metabolism and in the development of addiction under baseline conditions, indicating that dopamine function in the brain is well-protected from perturbation. However, the role of COMT becomes more important when the dopaminergic system is challenged, such as by pharmacological manipulation.

Crystallization as a Tool for Controlling and Designing Properties of Pharmaceutical Solids

The ability to deliver the drug to the patient in a safe, efficacious and cost-effective manner depends largely on the physicochemical properties of the active pharmaceutical ingredient (API) in the solid state. In this context, crystallization is of critical importance in pharmaceutical industry, as it defines physical and powder properties of crystalline APIs. An improved knowledge of the various aspects of crystallization process is therefore needed. The overall goal of this thesis was to gain better understanding of the relationships between crystallization, solid-state form and properties of pharmaceutical solids with a focus on a crystal engineering approach to design technological properties of APIs. Specifically, solid-state properties of the crystalline forms of the model APIs, erythromycin A and baclofen, and the influence of solvent on their crystallization behavior were investigated. In addition, the physical phenomena associated with wet granulation and hot-melting processing of the model APIs were examined at the molecular level. Finally, the effect of crystal habit modification of a model API on its tabletting properties was evaluated. The thesis enabled the understanding of the relationship between the crystalline forms of the model APIs, which is of practical importance for solid-state control during processing and storage. Moreover, a new crystalline form, baclofen monohydrate, was discovered and characterized. Upon polymorph screening, erythromycin A demonstrated high solvate-forming propensity thus emphasizing the need for careful control of the solvent effects during formulation. The solvent compositions that yield the desirable crystalline form of erythromycin A were defined. Furthermore, new examples on solvent-mediated phase transformations taking place during wet granulation of baclofen and hot-melt processing of erythromycin A dihydrate with PEG 6000 are reported. Since solvent-mediated phase transformations involve the crystallization of a stable phase and hence affect the dissolution kinetics and possibly absorption of the API these transformations must be well documented. Finally, a controlled-crystallization method utilizing HPMC as a crystal habit modifier was developed for erythromycin A dihydrate. The crystals with modified habit were shown to posses improved compaction properties as compared with those of unmodified crystals. This result supports the idea of morphological crystal engineering as a tool for designing technological properties of APIs and is of utmost practical interest.

Interactions of natural products with β-lactoglobulins, members of the lipocalin family

Natural products constitute an important source of new drugs. The bioavailability of the drugs depends on their absorption, distribution, metabolism and elimination. To achieve good bioavailability, the drug must be soluble in water, stable in the gastrointestinal tract and palatable. Binding proteins may improve the solubility of drug compounds, masking unwanted properties, such as bad taste, bitterness or toxicity, transporting or protecting these compounds during processing and storage. The focus of this thesis was to study the interactions, including ligand binding and the effect of pH and temperature, of bovine and reindeer β-lactoglobulin (βLG) with such compounds as retinoids, phenolic compounds as well as with compounds from plant extracts, and to investigate the transport properties of the βLG-ligand complex. To examine the binding interactions of different ligands to βLG, new methods were developed. The fluorescence binding method for the evaluation of ligand binding to βLG was miniaturized from a quartz cell to a 96-well plate. A method of ultrafiltration sampling combined with high-performance liquid chromatography was developed to assess the binding of compounds from extracts. The interactions of phenolic compounds or retinoids and βLG were investigated using the 96-well plate method. The majority of flavones, flavonols, flavanones and isoflavones and all of the retinoids included were shown to bind to bovine and reindeer βLG. Phenolic compounds, contrary to retinol, were not released at acidic pH. Those results suggest that βLG may have more binding sites, probably also on the surface of βLG. An extract from Camellia sinensis (L.) O. Kunze (black tea), Urtica dioica L. (nettle) and Piper nigrum (black pepper) were used to evaluate whether βLG could bind compounds from plant extracts. Piperine from P. nigrum was found to bind tightly and rutin from U. dioica weakly to βLG. No components from C. sinensis bound to βLG in our experiment. The uptake and membrane permeation of bovine and reindeer βLG, free and bound with retinol, palmitic acid and cholesterol, were investigated using Caco-2 cell monolayers. Both bovine and reindeer βLG were able to cross the Caco-2 cell membrane. Free and βLG-bound retinol and palmitic acid were transported equally, whereas cholesterol could not cross the Caco-2 cell monolayer free or bound to βLG. Our results showed that βLG can bind different natural product compounds, but cannot enhance transport of retinol, palmitic acid or cholesterol through Caco-2 cells. Despite this, βLG, as a water-soluble binding protein, may improve the solubility of natural compounds, possibly protecting them from early degradation and transporting some of them through the stomach. Furthermore, it may decrease their bad or bitter taste during oral administration of drugs or in food preparations. βLG can also enhance or decrease the health benefits of herbal teas and food preparations by binding compounds from extracts.

Heated Nebulizer Microchips for Mass Spectrometry

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.

Upregulation and Functionality of Neuronal Nicotinic Acetylcholine Receptors

Cigarette smoking is, in developed countries, the leading cause of premature death. In tobacco smoke, the main addictive compound is nicotine, which in the brain binds to neuronal nicotinic acetylcholine receptors (neuronal nAChRs). These have been implicated in addiction, but also in several neurological disorders including Alzheimer's and Parkinson's diseases, Tourette's syndrome, attention-deficit hyperactivity disorder (ADHD), schizophrenia, pain, depression, and autosomal-dominant noctural frontal lobe epilepsy; all of which makes nAChRs an intriguing target of study. Chronic treatment with nicotine leads to an increase in the number of nAChRs (upregulation) in the brain and changes their functionality. Changes in the properties of nAChRs are likely to occur in smokers as well, since they are exposed to nicotine for long periods of time. Several nAChR subtypes likely play a role in the formation of nicotine addiction by participating in the release of dopamine in the striatum. The aim of this study was to clarify at cellular level the changes in nAChR characteristics resulting from chronic nicotine treatment. SH-SY5Y cells, endogenously several nAChR-expressing, and SH-EP1-h-alfa7 cells, transfected with the alfa 7 nAChR subunit gene were treated chronically with nicotine. The localisation of alfa 7 and beta2 subunits was studied with confocal and electron microscopy. Functionality of nAChRs was studied with calcium fluorometry. Effects of long-term treatment with opioid compounds on nAChRs were studied by means of ligand binding. Confocal microscopy showed that in SH-SY5Y cells, alfa7 and beta2 subunits formed clusters, unlike the case in SH-EP1-h alfa7 cells, where alfa7 nAChRs were distributed more diffusely. The majority of nAChR subunits localised on endoplasmic reticulum (ER). The isomers of methadone acted as agonists at alfa7 nAChRs. Acute morphine challenge also stimulated nAChRs. Chronic treatment with methadone or morphine led to an increased number of nAChRs. In animal studies, mice received nicotine for 7 weeks. Electron microscopical analysis of the localisation of nAChRs showed in the striatum that alfa7 and beta2 nAChR subunits localised synaptically, extrasynaptically, and intracellularly, with the majority localising extrasynaptically. Chronic nicotine treatment caused an increase in the number of nAChR subunits at all studied locations. These results suggest that the alfa7 nAChR and beta2 subunit-containing nAChRs respond to chronic nicotine treatment differently. This may indicate that the functional balance of various nAChR subtypes in control of the release of dopamine is altered as a result of chronic nicotine treatment. Compounds binding both to opioid and nACh receptors may be of clinical importance.

Community Pharmacies and the Needs of Mobile EU Citizens - A study on Finns living in Spain

Migration within the European Union (EU) has increased since the Union was established. Community pharmacies provide open access to health care services and can be the first, most frequently used or even the only contact with a nation s health care system among mobile community residents. In some of the mass-migration areas in Southern Europe, most of the customers may represent mobile citizens of foreign background. This has not always been taken into consideration in the development of community pharmacy services. Mobile patients have been on the EU's health policy agenda, but they have seldom been mentioned in the context of community pharmacies. In most of the EU member states, governments control the specific legislation concerning community pharmacies and there is no harmonised pharmaceutical policy or consistent minimal standards for community pharmacy services in the EU. The aim of this study was to understand medication use, the role of community pharmacies and the symptom mitigation process of mobile community residents. Finns living in Spain were used as an example to examine how community pharmacies in a EU member state meet the needs of mobile community residents. The data were collected by a survey in 2002 (response rate 53%, n= 533) and by five focus group discussions in 2006 (n=30). A large number (70%) of the respondents had moved to Spain for health reasons and suffered from chronic morbidity. Community pharmacies had an important role in the healthcare of mobile community residents and the respondents were mostly satisfied with these services. However, several medication safety risks related to community pharmacy practices were identified: 1) Availability of prescription medicines without prescription (e.g., antibiotics, sleeping pills, Viagra®, asthma medications, cardiovascular medicines, psoriasis medicines and analgesics); 2) Irrational use of medicines (e.g., 41% of antibiotic users had bought their antibiotics without a prescription, and the most common reasons for antibiotic self-medication were symptomatic common colds and sore throats); 3) Language barriers between patients and pharmacy professionals; 4) Lack of medication counselling; 5) Unqualified pharmacy personnel providing pharmacotherapy. A fifth of the respondents reported experiencing problems during pharmacy visits in Spain, and the lack of a common language was the source of most of these problems. The findings of this study indicate that regulations and their enforcement can play a crucial role in actually assuring the rational and safe use of medicines. These results can be used in the development of pharmaceutical and healthcare policies in the EU. It is important to define consistent minimum standards for community pharmacy services in the EU. Then, the increasing number of mobile community residents could access safe and high quality health care services, including community pharmacy services, in every member state within the EU.

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.

Die Personennamen und Titel der mittelmongolischen Dokumente : Eine lexikalische Untersuchung

The present research is an investigation into the corpus of personal names and titles that are found in sources from the Middle Mongolian period, that is the time from the 13th to the beginning of the 15th century. The entry for every name or title has been divided into three parts: occurence(s) of a given name in Middle Mongolian sources (primary sources), etymology, and occurence(s) in sources other than Middle Mongolian (secondary sources). Culturally and lingistically the corpus can be divided into six sub-groups: Mongolian, Turkic (Old, Middle and Modern), Arabo-Persian (Islamic), Indo-Iranian and Tibetan (Buddhist), as well as Chinese. Among these, the largest group is formed by Mongolian and Turkic, followed by Chinese (mostly titles), Indo-Iranian, Arabo-Persian and Tibetan. With regard to the primary and secondary occurences the research is based mainly on primary sources including text-publications and dictionaries. Every name or title is documented as completely as possible within a Central Asian framework. However, due to the divergency of the sources available as well as diachronical importance, each sub-group has been dealt with slightly differently, but consistently. The corpus of investigated names and titles gives a fairly correct picture of the multi-ethnical composition of the Mongolian world-empire. It also shows the foreign influences on Mongolian names and titles, being in this respect a mirror of the influences that are visible in other parts of the Middle Mongolian culture too. Furthermore, the investigated corpus reflects the transitory stage of the 13th to 15th century in Central Asian history, and includes thus material from the past (Indo-Iranian, Old and Middle Turkic), and material that points to the future (Arabo-Persian, Tibetan, Modern Turkic).

Huellas de Eros y Thánatos en la narrativa de Diamela Eltit : La palabra en movimiento en el juego entre tropos, metáforas y deconstrucciones lingüísticas

Väitöskirja analysoi espanjan kielen dekonstruktioita ruumiin metaforista ja troopeista koostuvassa aineistossa chileläisen kirjailijan Diamela Eltitin (1949 -) neljässä romaanissa: Lumpérica (1983), Vaca sagrada (1991), El infarto del alma (1994) ja Los trabajadores de la muerte (1998). Näkökulma on kielen muutoksessa Eltitin proosassa 1980- ja 1990-luvuilla alkaen kokeellisesta huippuvaiheesta 1983, jolloin hän julkaisi esikoisromaaninsa Lumpérica. Tutkimus korostaa Eltitin romaanien historiallista arvoa, kirjallisuuden tapaa murtaa kielen rakenteita ja sitä miten tämä murros kytkeytyy taideteoreettiseen muutokseen kulttuuridiskursseissa. Tutkimus tarkastelee Eltitin kehityskaarta kenraali Augusto Pinochetin sotilasvallankaappauksesta 1973 halki sotilashallituksen kauden (1973-1990) aina kansalaisyhteiskunnan vahvistumiseen ja vuoteen 1998. Tutkimus analysoi ruumiin troopeista ja metaforista koostuvaa tutkimusaineistoa lingvistiikan, kirjallisuustieteen, historian ja sukupuolen tutkimuksen monitieteisessä viitekehyksessä. Sen vuoksi väitöskirja liittyy espanjalaisen filologian, yleisen kirjallisuustieteen, Latinalaisen Amerikan tutkimuksen ja naistutkimuksen oppiaineisiin. Kolme tärkeintä oppiteoreettista runkoa ovat lingvistinen strukturalismi, dekonstruktio ja feministiset kirjallisuusteoriat. Dekonstruktiivinen lähestymistapa tekstiin korostaa kielen merkityksen muodostumisen filosofista perustaa. Se pyrkii selvittämään, miten merkitys muodostuu kirjoittajan, tekstin ja lukijan välillä. Tekstikritiikki koostuu semanttisesta ja dekonstruktiivisesta tekstianalyysistä, jonka metodologisen mallin perusta on tanskalaisen kielitieteilijän Louis Hjelmslevin (1899-1965) kielitieteellinen malli. Väitös ei käytä mallia suoraan, vaan soveltaa sitä kaunokirjallisuuden tutkimukseen. Oppiteoreettisen viitekehyksen osalta tutkimus sijoittuu strukturalismin ja poststrukturalismin murrokseen. Tutkimus korostaa Eltitin radikaalia muotokieltä ja teatraalisuutta, hänen kielensä visuaalisuutta ja ruumiin metaforien eroottista jännitettä, mikä ilmenee mm. falloksen metaforaksi tulkitun hehkuvan valon kuvissa romaanissa Lumpérica. Vanhat kreikkalaiset myytit Éros ja Thánatos kasvavat esille länsimaisen taidehistorian perinteestä ja kontekstualisoituvat uusiksi kielikuviksi Chilen kirjallisessa maaperässä. Ne muodostavat Eltitin taiteellisen tuotannon pysyvän aihepiirin ja luovat teoksiin synkkää ja karua virettä sekä tummia ja eroottisia sävyjä. Tutkimus osoittaa, että Eltit dekonstruoi kieltä, mutta dekonstruktiot eivät ole jatkuvia eivätkä samanlaisia kaikissa romaaneissa. Kielellisten dekonstruktioiden variaatio on laaja eikä Eltit murra kielen syntaktisia ja morfologisia rakenteita kaikissa teksteissään. Tutkimuksen perusteella väitän, että Eltitin kirjoituksesta puhuttaessa useat tutkijat käyttävät epämääräisesti dekonstruktio-termiä. Useiden tutkijoiden toteamus dekonstruktiosta Diamela Eltitin kirjallisessa tuotannossa pysyvänä piirteenä on epätäsmällinen. Sen sijaan dekonstruktiivinen kirjoitus tarkoittaa Eltitillä laajasti vaihtelevaa lähestymistapaa kieleen, mikä ilmenee kehityslinjana hänen tuotannossaan ja eri tavoin jokaisessa teoksessa.

Ufologia ja ufokokemukset uskonnollisina ilmiönä : Teoreettinen tutkimus

The main question of my doctoral thesis is whether ufology and UFO experiences are or can be explained as religious phenomena. My research is theoretical in the sense that I combine and systematise cultural scientific knowledge concerning the religiosity of ufology and UFO experiences and complete this theoretical effort with empirical subject matter. The research material for my study consists of theoretical literature and empirical texts written by ufologists and those who have had UFO experiences. I defined the material in a way that it became full and extensive with regard to ufology, stories about UFO experiences and the cultural scientific literature concerning them. In addition, I present a source criticism for the literature because it is in part informal. The method is analysing and synthesising the material in the context of spiral of hermeneutic inferential process. Definitions of religion, ufology and UFO experience, developed by myself, serve as guide lines for the process. The conclusions of my research are as follows. For the most part, ufology and UFO experiences belong to the category of religion and only a fraction of these instances can be explained as something else, for example psychiatric phenomena. From the religious viewpoint I explain ufology and UFO experiences on four different but interlinked levels: historical, comparative, sociological and psychological. Historically ufology and UFO experiences include esoteristic, Christian and folk religious elements. In addition UFO experiences have significant similarities with folk religious stories and shamanistic experiences. From the perspective of the sociology, of religion ufology and UFO experiences can be analysed as products of our scientific and technological Western culture. Social crisis and social psychological group mechanisms affect the appearance of ufological ideas and UFO experiences. Psychologically, in the background of religious UFO experiences there can be found several factors, such as wishful thinking. Concerning UFO sightings these are misinterpretations of certain ordinary and some rare or exotic natural and technical phenomena. Intense UFO experiences, such as UFO abductions, are stimulated for the most part by hallucinations, sleep paralysis disorders, lively fantasies (in case of fantasy prone personalities) and false memories. In group cases social pressure, small group delusion and the guilt of exposing the true nature of a story come into play. A UFO experience can be traumatising because of certain inferential mechanisms and cognitive dissonance involved in the process of conversion as a UFO experiencer. UFO religiosity is a cross cultural, widespread and a significant field of phenomena, which can offer insight about religious developments in the future. However, UFO religiosity has not been studied extensively. This research is one effort to address this lack of documentation. The motivation behind my thesis was to make ufology and UFO experiences more understandable.

Dancing and Professional Dancers in Roman Egypt

The main aim of the study is to create a many-sided view of dancing in Roman Egypt (1st - early 4th centuries AD) and especially of the dancers who earned their living by dancing as hired performers. Even though dancers and other performers played a central part in many kinds of festivities throughout the ancient world, research on ancient professional dancers is rare and tends to rest on the ancient literature, which reflects the opinions of the elite. Documentary written sources (i.e., papyri, ostraka) the core of the present study are mentioned rather superficially, easily resulting in a stereotypical view of the dancers. This study will balance the picture of professional dancers in antiquity and of ancient dancing in a more general sense. The second aim characterizes this study as basic research: to provide a corpus of written sources from Greco-Roman Egypt on dancing and to discuss pictorial sources contemporary with the texts. The study also takes into account the theoretical discussion that centres on dancing as a nonverbal communicative mode. Dancers are seen as significant conveyors of social and cultural matters. This study shows that dancers were hired to perform especially in religious contexts, where the local associations on the village level also played an important part as the employers of the performers. These performers had a better standard of living in economic terms than the average hired worker, and dancers were better paid than other performers. In the Egyptian villages and towns, where the dancers performed and lived, the dancers do not seem to have been marginal because they were professionals or because of some ethnic or social background. However, their possible marginality may have occurred for reasons related to the practicalities of their profession (e.g., the itinerant life style). The oriental background of performers was a literary topos reflecting partly the situation in the centres of the empire, especially Rome, where many performers were of other than Roman origin. The connection of dancing, prostitution and slavery reflects the essential link between dance, body and gender: dancers are equated with such professions or socio-legal statuses where the body is the focus of attention, a commodity and a source of sensual pleasure; this dimension is clearly observable in ancient literature. According to the Egyptian documentary sources, there is no watertight evidence that professional dancers would have been engaged in prostitution and very little, if any, evidence that the disapproval of the professional dancers expressed by the ancient authors was shared by the Egyptians. From the 4th century onwards the dancers almost disappear from the documentary sources, reflecting the political and religious changes in the Mediterranean east.

Il mundus muliebris nelle fonti latine e nei contesti Pompeiani

The subject of the study is the classical Latin concept 'mundus muliebris', usually translated simply as women’s toiletry items. The task of the research is, on one hand, to find a more accurate and comprehensive literary definition for the concept as used in the early Imperial period, and on the other, to examine whether it is possible to find corresponding groupings of material objects among the finds from Pompeian houses destroyed by the eruption of Mount Vesuvius in AD 79. The study is based on two different bodies of evidence, literary and material, and consequently uses two independent methods of research. In the philological part of the study, all occurrences of the concept 'mundus muliebris' in classical Latin texts were identified and analysed in their proper literary context, paying special attention to information about the nature of the objects included (name, owner, quantity, value, location in the house). On the basis of this analysis, mirrors were chosen as the key elements of the archaeological research, being ̶ hypothetically ̶ the most probable objects to be found among any extant 'mundus muliebris' contexts in Pompeian houses. In the archaeological part of the study, all mirrors deposited in the Archaeological Storerooms of Pompeii, mostly unpublished, were examined, together with their original find contexts. For more detailed documentation, classification, as well as quantitative and functional analysis, the fifty-nine best preserved household or shop contexts were chosen. Among these contexts, only a few ‘ideal’ groups closely corresponding to the literary definitions were found. However, in most cases a functional artifact pattern of toiletry items could indeed be found grouped together with the mirror. The arrangement of the contexts in the domestic space also revealed a clear pattern. Firstly, the contexts consistently seem to be found in the place of storage, inside locked boxes, not in the place of use. Secondly, they show that for the storage of such objects small closed rooms flanking the main entrance of the house were preferred. Culturally, 'mundus muliebris' can be described as a very complex multi-layered concept intimately interrelated with the female gender, an instrument of its bodily creation and a symbol of its nature. Concretely, it has at its core mirrors and instruments for the care of skin and hair, and includes, in more technical definitions, washing equipment as well. In the Roman domus, lacking specific women’s quarters, this box containing toiletries and other personal objects could be defined as the true, although mobile, private space of the household’s female members.

Precarious Creativity: Global Media, Local Labor

Precarious Creativity examines the seismic changes confronting media workers in an age of globalization and corporate conglomeration. This pathbreaking anthology peeks behind the hype and supposed glamor of screen media industries to reveal the intensifying pressures and challenges confronting actors, editors, electricians, and others. The authors take on pressing conceptual and methodological issues while also providing insightful case studies of workplace dynamics regarding creativity, collaboration, exploitation, and cultural difference. Furthermore, it examines working conditions and organizing efforts on all six continents, offering broad-ranging and comprehensive analysis of contemporary screen media labor in such places as Lagos, Prague, Hollywood, and Hyderabad. The collection also examines labor conditions across a range of job categories that includes, for example, visual effects, production services, and adult entertainment. With contributions from such leading scholars as John Caldwell, Vicki Mayer, Herman Gray, and Tejaswini Ganti, Precarious Creativity offers timely critiques of media globalization while also intervening in broader debates about labor, creativity, and precarity.

Roomalaista oikeutta kreikaksi 500-luvun Palestiinassa : Eräitä lakitermejä papyruksessa P. Petra inv. 83

Tutkimuksen tarkoituksena on analysoida eräitä lakitermejä, jotka esiintyvät papyruksessa P. Petra inv. 83. Kyseinen dokumentti, joka sisältää sopimuksen kahden naapuruksen välisen kiistan lopettamiseksi, ajoittuu todennäköisesti vuodelle 574 jKr. ja se kuuluu Jordanian Petrasta vuonna 1993 löydettyyn hiiltyneeseen papyrusarkistoon. Papyrus on tällä hetkellä vielä julkaisematon, ja tämä työ on osa siihen liittyvää perustutkimusta, jonka tarkoituksena on toisaalta selittää tekstin itsensä sisältö, toisaalta arvioida sen antaman informaation merkitystä laajemmassa historiallisessa kontekstissa. Papyrus on kirjoitettu kreikaksi, Bysantin eli Itä-Rooman valtakunnan virallisella kielellä, mutta itse lakitermeistä suurin osa liittyy alun perin latinan kielellä luotuun roomalaiseen oikeuteen. Paikallinen väestö puolestaan oli seemiläistä alkuperää, jolla ei ainoastaan ollut oma kieli, vaan jolla oli ollut ennen valtakuntaan liittämistä omat oikeustraditionsakin. Niinpä papyruksessa esiintyvien termien tutkimuksen kautta nousevat esille monenlaiset laajemmatkin kysymyksenasettelut. Lakitermejä analysoidaan pääasiassa kolmesta näkökulmasta. Ensisijaisena pyrkimyksenä on selvittää niiden tarkka merkitys asiayhteydessään, joka papyruksen fragmentaarisuuden vuoksi ei ole etukäteen selvä, ja siten edistää tekstissä puheena olevien asianhaarojen ymmärtämistä. Toiseksi termien käyttöä koskevat tulokset suhteutetaan yleiseen oikeushistoriaan ja pyritään arvioimaan niiden merkitystä Petrassa käytössä olleen oikeusjärjestelmän kannalta. Kolmas näkökulma on kielitieteellinen, sillä termien käyttö papyruksessa on nähtävä osana laajempaa kehitystä, jossa roomalaisen oikeuden vähittäinen muuttuminen bysanttilaiseksi johti kielten vaihtumiseen ja koko juridisen käsitteistön siirtymiseen latinasta kreikkaan. Siksi tässä työssä käytetään itse papyruksen analyysin lisäksi laajaa vertailumateriaalia, joka koostuu ennen kaikkea roomalaisesta ja bysanttilaisesta lakikirjallisuudesta sekä dokumentaarisesta lähdeaineistosta, etenkin egyptiläisistä papyruksista. Niin tässä papyruksessa kuin muissakin kreikankielisissä lähteissä esiintyvät roomalaiseen oikeuteen liittyvät termit voidaan jaotella suoriin lainoihin, käännöslainoihin sekä komparaatiolainoihin. Jälkimmäisillä tarkoitetaan kreikan kielessä jo aiemmin käytössä olleita termejä, jotka eivät sananmukaiselta merkitykseltään vastaa latinalaisia, mutta joita alettiin käyttää jonkin latinalaisen termin vastineina. Tutkimus tekee selväksi, että olipa kyse mistä lainakategoriasta tahansa, lakitermien siirtyessä kielestä toiseen tapahtui yleensä semanttisia muutoksia eikä termejä aina käytetty samalla tavalla kuin alkukielessä. Merkityskenttä saattoi esimerkiksi supistua taikka laajentua tai sanalle saattoi kehittyä lainautumisen jälkeen täysin uusiakin merkityksiä. Oikeushistorian suhteen on huomioitava ero virallisten säännösten ja provinsseissa noudatettujen käytäntöjen välillä. Kaiken kaikkaan Petra näyttää kuitenkin olleen kiinteä osa Bysantin valtakuntaa, jonka lakeja ainakin pääpiirteissään noudatettiin. Kaikkien termien käytötavat eivät tosin ole johdettavissa suoraan virallisiin lakikorpuksiin, mutta ne eivät myöskään sodi niitä vastaan. Roomalaisen oikeuden tuntemus näyttää olleen Petrassa jopa parempaa kuin esimerkiksi Egyptissä. Mitä tulee papyruksessa puheena oleviin konkreettisiin asianhaaroihin, termien merkityksen ymmärtäminen selventää joidenkin aspektien pääpiirteitä, kun taas yksityskohdat jäävät tekstin fragmentaarisuuden takia useimmiten epäselviksi. Avainsanat: papyrologia, Petra, roomalainen oikeus, terminologia, kreikan kieli, latinan kieli, lainasanat

Japanese Video Game Localization : A Case Study of Sony's Sairen Series

This thesis is a comparative case study in Japanese video game localization for the video games Sairen, Sairen 2 and Sairen Nyûtoransurêshon, and English-language localized versions of the same games as published in Scandinavia and Australia/New Zealand. All games are developed by Sony Computer Entertainment Inc. and published exclusively for Playstation2 and Playstation3 consoles. The fictional world of the Sairen games draws much influence from Japanese history, as well as from popular and contemporary culture, and in doing so caters mainly to a Japanese audience. For localization, i.e. the adaptation of a product to make it accessible to users outside the original market it was intended for in the first place, this is a challenging issue. Video games are media of entertainment, and therefore localization practice must preserve the games’ effects on the players’ emotions. Further, video games are digital products that are comprised of a multitude of distinct elements, some of which are part of the game world, while others regulate the connection between the player as part of the real world and the game as digital medium. As a result, video game localization is also a practice that has to cope with the technical restrictions that are inherent to the medium. The main theory used throughout the thesis is Anthony Pym’s framework for localization studies that considers the user of the localized product as a defining part of the localization process. This concept presupposes that localization is an adaptation that is performed to make a product better suited for use during a specific reception situation. Pym also addresses the factor that certain products may resist distribution into certain reception situations because of their content, and that certain aspects of localization aim to reduce this resistance through significant alterations of the original product. While Pym developed his ideas with mainly regular software in mind, they can also be adapted well to study video games from a localization angle. Since modern video games are highly complex entities that often switch between interactive and non-interactive modes, Pym’s ideas are adapted throughout the thesis to suit the particular elements being studied. Instances analyzed in this thesis include menu screens, video clips, in-game action and websites. The main research questions focus on how the games’ rules influence localization, and how the games’ fictional domain influences localization. Because there are so many peculiarities inherent to the medium of the video game, other theories are introduced as well to complement the research at hand. These include Lawrence Venuti’s discussions of foreiginizing and domesticating translation methods for literary translation, and Jesper Juul’s definition of games. Additionally, knowledge gathered from interviews with video game localization professionals in Japan during September and October 2009 is also utilized for this study. Apart from answering the aforementioned research questions, one of this thesis’ aims is to enrich the still rather small field of game localization studies, and the study of Japanese video games in particular, one of Japan’s most successful cultural exports.