Effect of water vapour stabilization of raw materials on the quality of the inhalation product

Generation of raw materials for dry powder inhalers by different size reduction methods can be expected to influence physical and chemical properties of the powders. This can cause differences in particle size, size distribution, shape, crystalline properties, surface texture and energy. These physical properties of powders influence the behaviour of particles before and after inhalation. Materials with an amorphous surface have different surface energy compared to materials with crystalline surface. This can affect the adhesion and cohesion of particles. Changes in the surface nature of the drug particles results in a change in product performance. By stabilization of the raw materials the amorphous surfaces are converted into crystalline surfaces. The primary aim of the study was to investigate the influence of the surface properties of the inhalation particles on the quality of the product. The quality of the inhalation product is evaluated by measuring the fine particle dose (FPD). FDP is the total dose of particles with aerodynamic diameters smaller than 5,0 μm. The secondary aim of this study was to achieve the target level of the FPD and the stability of the FPD. This study was also used to evaluate the importance of the stabilization of the inhalation powders. The study included manufacturing and analysing drug substance 200 μg/dose inhalation powder batches using non-stabilized or stabilized raw materials. The inhaler formulation consisted of micronized drug substance, lactose <100μm and micronized lactose <10μm. The inhaler device was Easyhaler®. Stabilization of the raw materials was done in different relative humidity, temperature and time. Surface properties of the raw materials were studied by dynamic vapour sorption, scanning electron microscopy and three-point nitrogen adsorption technique. Particle size was studied by laser diffraction particle size analyzer. Aerodynamic particle size distribution from inhalers was measured by new generation impactor. Stabilization of all three raw materials was successful. A clear difference between nonstabilized and stabilized raw materials was achieved for drug substance and lactose <10μm. However for lactose <100μm the difference wasn’t as clear as wanted. The surface of the non-stabilized drug substance was more irregular and the particles had more roughness on the surface compared to the stabilized drug substances particles surface. The surface of the stabilized drug particles was more regular and smoother than non-stabilized. Even though a good difference between stabilized and non-stabilized raw materials was achieved, a clear evidence of the effect of the surface properties of the inhalation particles on the quality of the product was not observed. Stabilization of the raw materials didn’t lead to a higher FPD. Possible explanations for the unexpected result might be too rough conditions in the stabilization of the drug substance or smaller than wanted difference in the degree of stabilization of the main component of the product <100μm. Despite positive effects on the quality of the product were not seen there appears to be some evidence that stabilized drug substance results in smaller particle size of dry powder inhalers.

Ruumiinkuvia! : Suomalainen performanssi- ja kehotaide 1980- ja1990-luvulla psykoanalyysin valossa

My PhD-thesis Body Images! Psychoanalytical Analysis of Finnish Performance and Body Art in the 1980s and 1990s considers Finnish performance and body art performed mainly by visual artists. In Part I, I chart the historical construction of performance art and its extension since the beginning of the 21st century. There are several wievs of the historical background of performance art. I introduce three different genealogies of performance art. One is Rose-Lee Goldberg s view. She connects performance art with the European avant-garde already at the beginning of the 20th century from futurists and dadaists to Russian avant-garde and the Bauhaus. I prefer to present performance art as contemporary art, which began to take shape in connection with visual arts in the 1950s and 1960s. The focus on the body is apparent in nearly all performance art. Nevertheless, throug the concept of body art I want to empasize the artist s body as the place of art. Body art (as part of performance art) functions as thematic and interpretive concept, which allows me to focus on performances where the questions of body image, narcissism, desire, language and pleasure are incorporated in particular intensive ways. In Part II, I explore the arrival of performance art in Finnish visual arts in the 1980s. I study the new generation s relation to earlier Finnish happenings (1960s) and performative actions in 1970 s. I briefly introduce performance groups of the 1980s art scene and consider their reception in media. The main focus is on the group Jack Helen Brut, in which I see many similarities to the so- called Theatre of Images. The goal of this part II is to provide historical context for the performance analysis that follows. In Part III, I develop the concept of body image which is my main theoretical term. The concept of body image is used according to Lacanian psychoanalytical theory, especially his considerations of mirror stages. My first mapping of body image, which I call imaginary body image, is based on Lacan s famous mirror stage article (1949). According to my reading, body image is narcistic and aggressive. The important concepts here are ego, imaginary, méconnaisance and alienation. In 1953 Lacan began to develop different version on mirror stage, in which he emphasized the primacy of symbolic dimension. It is not image, but language which constructs the foundations of body image. Central concepts in this chater are Other as language, ego-ideal, demand and desire. In the last chapter I connect the third version of the mirror stage to concepts of gaze, phantasy, real, jouissance and object a. In previous chapters I had considered body image in relation to ego. Now I explore it in relation to subject. In my reading the body image is fragile phenomen, which oscillates between yearning for coherence and phantasies of fragmented images. Part IV of the thesis begins with an introduction to the central concepts and debates in performace studies over the last few decades. Important concepts are presence, performativity and theatricality. The main substance of my thesis, however, is the performance analysis, which focuses on works by three Finnish artists and one Finnish group. The first analysis concerns the performance (1992) of Kimmo Schroderus. I discuss the relationship between narcissism and body art and the changes in demands projected on body images of men in recent decades in a Euro-American context. I also explore this performance in relation to the myth of Narcissus, which I reinterpret through Narcissus s aggression against his own body. The group Homo S is the main subject of the next analysis. I discuss the relationship between feminist art and performance art, especially in the United States in the 1960s and 1970s. Homo S is different from this early performance art because of its anarchism, humor and rejection of all ideals. Homo S characterizes its performance Body Body (1983) as liberating vulgar feminism . Sociality and performance of erotic relations between women are central in Body Body. Pia Lindman s performances are the subjects of my third analysis. I study three of her performances: Olen muoto (1993), 17 and in love (1994) and Arranged views (1995). I interpret these performances as efforts to disperse the imaginary and symbolic structures of the body image. She constructs the peculiar object a and phantasy space of her own. In the last analysis I move from questions of image and gaze to a study of language, sound and jouissance. I discuss at a general level the performance of orality and helplesness (Hilflosigkeit) in body art. The central elements in Pentti Otto Koskinen s performances are the ear, listening and receptive gestures and postions. Perseveraatio (1998) can be understood representing as submission to the super-ego s power, which compels one to enjoy. I examine particularly closely the performance Maissi on hyvää ei missään nimessä maissia (1995), which I interpret as the return of a baby s body image to the liminal site of choice: language or jouissance?

Suunnittelunäkemys metsäorganisaatioissa ja sen vaikutus tietojärjestelmälle asetettaviin vaatimuksiin

Department of Forest Resource Management in the University of Helsinki has in years 2004?2007 carried out so-called SIMO -project to develop a new generation planning system for forest management. Project parties are organisations doing most of Finnish forest planning in government, industry and private owned forests. Aim of this study was to find out the needs and requirements for new forest planning system and to clarify how parties see targets and processes in today's forest planning. Representatives responsible for forest planning in each organisation were interviewed one by one. According to study the stand-based system for managing and treating forests continues in the future. Because of variable data acquisition methods with different accuracy and sources, and development of single tree interpretation, more and more forest data is collected without field work. The benefits of using more specific forest data also calls for use of information units smaller than tree stand. In Finland the traditional way to arrange forest planning computation is divided in two elements. After updating the forest data to present situation every stand unit's growth is simulated with different alternative treatment schedule. After simulation, optimisation selects for every stand one treatment schedule so that the management program satisfies the owner's goals in the best possible way. This arrangement will be maintained in the future system. The parties' requirements to add multi-criteria problem solving, group decision support methods as well as heuristic and spatial optimisation into system make the programming work more challenging. Generally the new system is expected to be adjustable and transparent. Strict documentation and free source code helps to bring these expectations into effect. Variable growing models and treatment schedules with different source information, accuracy, methods and the speed of processing are supposed to work easily in system. Also possibilities to calibrate models regionally and to set local parameters changing in time are required. In future the forest planning system will be integrated in comprehensive data management systems together with geographic, economic and work supervision information. This requires a modular method of implementing the system and the use of a simple data transmission interface between modules and together with other systems. No major differences in parties' view of the systems requirements were noticed in this study. Rather the interviews completed the full picture from slightly different angles. In organisation the forest management is considered quite inflexible and it only draws the strategic lines. It does not yet have a role in operative activity, although the need and benefits of team level forest planning are admitted. Demands and opportunities of variable forest data, new planning goals and development of information technology are known. Party organisations want to keep on track with development. One example is the engagement in extensive SIMO-project which connects the whole field of forest planning in Finland.

Sources and concentrations of volatile organic compounds

Volatile organic compounds (VOCs) have a great influence on tropospheric chemistry; they affect ozone formation and they or their reaction products are able to take part in secondary organic aerosol formation; some of the VOCs are themselves toxic. Knowing the concentrations and sources of different reactive volatile organic compounds is essential for the development of ozone control strategies and for studies of secondary organic aerosol formation. The objective of this work was to study volatile organic compounds in urban air, develop and validate determination methods for them, characterize their concentrations and estimate the contributions of different VOC sources. Of the different compound groups detected in the urban air of Helsinki, alkanes were found to have the highest concentrations, but when the concentrations were scaled against the reactivity with hydroxyl radicals (OH), aromatic hydrocarbons and alkenes were found to have the greatest effect on local chemistry. Comparisons with rural sites showed that concentrations at Utö and Hyytiälä were generally lower than those in Helsinki, especially for the alkenes and aromatic hydrocarbons, but concentrations of halogenated hydrocarbons at Utö and carbonyls at Hyytiälä were at the same level as in Helsinki. Most halogenated hydrocarbons do not have any significant sources in Helsinki, and carbonyls are formed in the atmosphere in the reactions of other VOCs, and are therefore also produced in other than urban areas. At Hyytiälä carbonyls were found to have an important role in the local chemistry. The contribution of carbonyls as an OH sink was higher than that of the monoterpenes and aromatic hydrocarbons. Based on the emission profile and concentration measurements, the contributions of different sources were estimated at urban (Helsinki) and residential (Järvenpää) sites using a chemical mass balance (CMB) receptor model. It was shown that it is possible to apply CMB in the case of a large number of different compounds with different properties. According to the CMB analysis, the major sources for these VOCs in Helsinki were traffic and distant sources. At the residential site in Järvenpää, the contribution due to traffic was minor, while distant sources, liquid gasoline and wood combustion made higher contributions. It was also shown that wood combustion can be an important source at some locations of VOCs usually considered as traffic-related compounds (e.g., benzene).

Inhomogeneity of asteroid 2008 TC3 (Almahata Sitta meteorites) revealed through magnetic susceptibility measurements

Magnetic susceptibility measurements were performed on freshly fallen Almahata Sitta meteorites. Most recovered samples are polymict ureilites. Those found in the first four months since impact, before the meteorites were exposed to rain, have a magnetic susceptibility in the narrow range of 4.92 ± 0.08 log 10-9 Am2/kg close to the range of other ureilite falls 4.95 ± 0.14 log 10-9 Am2/kg reported by Rochette et al. (2009). The Almahata Sitta samples collected one year after the fall have similar values (4.90 ± 0.06 log 10-9 Am2/kg), revealing that the effect of one-year of terrestrial weathering was not severe yet. However, our reported values are higher than derived from polymict (brecciated) ureilites 4.38 ± 0.47 log 10-9 Am2/kg (Rochette et al. 2009) containing both falls and finds confirming that these are significantly weathered. Additionally other fresh-looking meteorites of non-ureilitic compositions were collected in the Almahata Sitta strewn field. Magnetic susceptibility measurements proved to be a convenient non-destructive method for identifying non-ureilitic meteorites among those collected in the Almahata Sitta strewn field, even among fully crusted. Three such meteorites, no. 16, 25, and 41, were analyzed and their composition determined as EH6, H5 and EL6 respectively (Zolensky et al., 2010). A high scatter of magnetic susceptibility values among small (< 5 g) samples revealed high inhomogeneity within the 2008 TC3 material at scales below 1-2 cm.

Rough Justice or Zero Tolerance? - Reassessing the Nature of Copyright in Light of Collective Licensing (Part I)

Starting point in the European individualistic copyright ideology is that an individual author creates a work and controls the use of it. However, this paper argues that it is (and has always been) impossible to control the use of works after their publication. This has also been acknowledged by the legislator, who has introduced collective licensing agreements because of this impossibility. Since it is impossible to rigorously control the use of works this writing "Rough Justice or Zero Tolerance - Reassessing the Nature of Copyright in Light of Collective Licensing" examines what reality of copyright is actually about. Finding alternative (and hopefully more "true") ways to understand copyright helps us to create alternative solutions in order to solve possible problems we have as it comes e.g. to use of content in online environment. The paper makes a claim that copyright is actually about defining negotiation points for different stakeholders and that nothing in the copyright reality prevents us from defining e.g. a new negotiation point where representatives of consumers would meet representatives of right holders in order to agree on the terms of use for certain content types in online environment.

Discovery of oxidative enzymes for food engineering : Tyrosinase and sulfhydryl oxidase

Enzymes offer many advantages in industrial processes, such as high specificity, mild treatment conditions and low energy requirements. Therefore, the industry has exploited them in many sectors including food processing. Enzymes can modify food properties by acting on small molecules or on polymers such as carbohydrates or proteins. Crosslinking enzymes such as tyrosinases and sulfhydryl oxidases catalyse the formation of novel covalent bonds between specific residues in proteins and/or peptides, thus forming or modifying the protein network of food. In this study, novel secreted fungal proteins with sequence features typical of tyrosinases and sulfhydryl oxidases were iden-tified through a genome mining study. Representatives of both of these enzyme families were selected for heterologous produc-tion in the filamentous fungus Trichoderma reesei and biochemical characterisation. Firstly, a novel family of putative tyrosinases carrying a shorter sequence than the previously characterised tyrosinases was discovered. These proteins lacked the whole linker and C-terminal domain that possibly play a role in cofactor incorporation, folding or protein activity. One of these proteins, AoCO4 from Aspergillus oryzae, was produced in T. reesei with a production level of about 1.5 g/l. The enzyme AoCO4 was correctly folded and bound the copper cofactors with a type-3 copper centre. However, the enzyme had only a low level of activity with the phenolic substrates tested. Highest activity was obtained with 4-tert-butylcatechol. Since tyrosine was not a substrate for AoCO4, the enzyme was classified as catechol oxidase. Secondly, the genome analysis for secreted proteins with sequence features typical of flavin-dependent sulfhydryl oxidases pinpointed two previously uncharacterised proteins AoSOX1 and AoSOX2 from A. oryzae. These two novel sulfhydryl oxidases were produced in T. reesei with production levels of 70 and 180 mg/l, respectively, in shake flask cultivations. AoSOX1 and AoSOX2 were FAD-dependent enzymes with a dimeric tertiary structure and they both showed activity on small sulfhydryl compounds such as glutathione and dithiothreitol, and were drastically inhibited by zinc sulphate. AoSOX2 showed good stabil-ity to thermal and chemical denaturation, being superior to AoSOX1 in this respect. Thirdly, the suitability of AoSOX1 as a possible baking improver was elucidated. The effect of AoSOX1, alone and in combi-nation with the widely used improver ascorbic acid was tested on yeasted wheat dough, both fresh and frozen, and on fresh water-flour dough. In all cases, AoSOX1 had no effect on the fermentation properties of fresh yeasted dough. AoSOX1 nega-tively affected the fermentation properties of frozen doughs and accelerated the damaging effects of the frozen storage, i.e. giving a softer dough with poorer gas retention abilities than the control. In combination with ascorbic acid, AoSOX1 gave harder doughs. In accordance, rheological studies in yeast-free dough showed that the presence of only AoSOX1 resulted in weaker and more extensible dough whereas a dough with opposite properties was obtained if ascorbic acid was also used. Doughs containing ascorbic acid and increasing amounts of AoSOX1 were harder in a dose-dependent manner. Sulfhydryl oxidase AoSOX1 had an enhancing effect on the dough hardening mechanism of ascorbic acid. This was ascribed mainly to the produc-tion of hydrogen peroxide in the SOX reaction which is able to convert the ascorbic acid to the actual improver dehydroascorbic acid. In addition, AoSOX1 could possibly oxidise the free glutathione in the dough and thus prevent the loss of dough strength caused by the spontaneous reduction of the disulfide bonds constituting the dough protein network. Sulfhydryl oxidase AoSOX1 is therefore able to enhance the action of ascorbic acid in wheat dough and could potentially be applied in wheat dough baking.

Drug epidemiology, interactions and pharmacogenetics : A post-mortem database study

Use of adverse drug combinations, abuse of medicinal drugs and substance abuse are considerable social problems that are difficult to study. Prescription database studies might fail to incorporate factors like use of over-the-counter drugs and patient compliance, and spontaneous reporting databases suffer from underreporting. Substance abuse and smoking studies might be impeded by poor participation activity and reliability. The Forensic Toxicology Unit at the University of Helsinki is the only laboratory in Finland that performs forensic toxicology related to cause-of-death investigations comprising the analysis of over 6000 medico-legal cases yearly. The analysis repertoire covers most commonly used drugs and drugs of abuse, and the ensuing database contains also background information and information extracted from the final death certificate. In this thesis, the data stored in this comprehensive post-mortem toxicology database was combined with additional metabolite and genotype analyses that were performed to complete the profile of selected cases. The incidence of drug combinations possessing serious adverse drug interactions was generally low (0.71%), but it was notable for the two individually studied drugs, a common anticoagulant warfarin (33%) and a new generation antidepressant venlafaxine (46%). Serotonin toxicity and adverse cardiovascular effects were the most prominent possible adverse outcomes. However, the specific role of the suspected adverse drug combinations was rarely recognized in the death certificates. The frequency of bleeds was observed to be elevated when paracetamol and warfarin were used concomitantly. Pharmacogenetic factors did not play a major role in fatalities related to venlafaxine, but the presence of interacting drugs was more common in cases showing high venlafaxine concentrations. Nicotine findings in deceased young adults were roughly three times more prevalent than the smoking frequency estimation of living population. Contrary to previous studies, no difference in the proportion of suicides was observed between nicotine users and non-nicotine users. However, findings of abused substances, including abused prescription drugs, were more common in the nicotine users group than in the non-nicotine users group. The results of the thesis are important for forensic and clinical medicine, as well as for public health. The possibility of drug interactions and pharmacogenetic issues should be taken into account in cause-of-death investigations, especially in unclear cases, medical malpractice suspicions and cases where toxicological findings are scarce. Post-mortem toxicological epidemiology is a new field of research that can help to reveal problems in drug use and prescription practises.