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

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

Space in Musical Semiosis : An Abductive Theory of the Musical Composition Process

Space in musical semiosis is a study of musical meaning, spatiality and composition. Earlier studies on musical composition have not adequately treated the problems of musical signification. Here, composition is considered an epitomic process of musical signification. Hence the core problems of composition theory are core problems of musical semiotics. The study employs a framework of naturalist pragmatism, based on C. S. Peirce’s philosophy. It operates on concepts such as subject, experience, mind and inquiry, and incorporates relevant ideas of Aristotle, Peirce and John Dewey into a synthetic view of esthetic, practic, and semiotic for the benefit of grasping musical signification process as a case of semiosis in general. Based on expert accounts, music is depicted as real, communicative, representational, useful, embodied and non-arbitrary. These describe how music and the musical composition process are mental processes. Peirce’s theories are combined with current morphological theories of cognition into a view of mind, in which space is central. This requires an analysis of space, and the acceptance of a relativist understanding of spatiality. This approach to signification suggests that mental processes are spatially embodied, by virtue of hard facts of the world, literal representations of objects, as well as primary and complex metaphors each sharing identities of spatial structures. Consequently, music and the musical composition process are spatially embodied. Composing music appears as a process of constructing metaphors—as a praxis of shaping and reshaping features of sound, representable from simple quality dimensions to complex domains. In principle, any conceptual space, metaphorical or literal, may set off and steer elaboration, depending on the practical bearings on the habits of feeling, thinking and action, induced in musical communication. In this sense, it is evident that music helps us to reorganize our habits of feeling, thinking, and action. These habits, in turn, constitute our existence. The combination of Peirce and morphological approaches to cognition serves well for understanding musical and general signification. It appears both possible and worthwhile to address a variety of issues central to musicological inquiry in the framework of naturalist pragmatism. The study may also contribute to the development of Peircean semiotics.

Meän tapa puhua : Tornionlaakso pellolaisnuorten subjektiivisena paikkana ja murrealueena

This folk linguistic and human geographic study deals with dialect awareness, dialect use and place attachment. The study discusses theoretical and methodological issues current in sociolinguistics suggesting that the study of attitudes should be regarded as a core area in the study of variation and change. Furthermore, it is suggested that instead of putting effort into improving mental mapping methodology (adopted into folk linguistics from behavioural geography of the 1960 s), the more up-to-date thinking of space in geography should be adopted. The region and the dialect are treated as perceptual constructs in the study. The dialect perceptions of high school seniors in the Finnish Tornio Valley are examined trough a triangulation method involving a questionnaire, interviews and dialect recognition test as the research methods. The h in non-initial syllables (e.g. lähethä(ä)n, saunhaan ~ sauhnaan let s go into sauna ) turns out, expectedly, as the most salient feature in the dialect awareness of the locals and in terms of local identity construction. This feature is no longer heard in most of the present dialects of Finnish but is still thriving in the Tornio Valley in the cross-border dialect area. The metathetic variant (saunhaan > sauhnaan into sauna , käymhään > käyhmään to go ) is a characteristic feature of the Tornio Valley dialect. However, individual differences have long been found in the use of the h. This study challenges the essentialist variationist view of social categories (gender) by analysing variation from a quantitative but emic and human geographic point of view. The study shows that the variation of the h is statistically significantly patterned in terms of the degree of feeling of insideness vs. outsideness. New light is shed on the gender differences found in earlier sociolinguistic studies: differences in dialect use between and inside gender groups are illuminated by the fact that, in this case, it is young women who are generally less attached to the local community than young men, but this does not hold for all the individuals. The ideological motivation for preservation of the h seems to be based on the imagined community of Tornio Valley covering both the Swedish and the Finnish valley area. The general image of the dialect area and it s speakers, the shared cognitive dialect boundaries of the locals and the particularly deep level of awaress of the linguistic variation of the h are notable resources of the Tornio valley identity. Hyperdialectic forms analogical to the most frequently attested metathetic forms are found in the interview data, predicting that in this dialect the h will be maintained also in the future.

Characterization of the mitochondrial active-site serine protein LACTB: filaments in the mitochondrial intermembrane space

Mitochondria have evolved from endosymbiotic alpha-proteobacteria. During the endosymbiotic process early eukaryotes dumped the major component of the bacterial cell wall, the peptidoglycan layer. Peptidoglycan is synthesized and maintained by active-site serine enzymes belonging to the penicillin-binding protein and the β-lactamase superfamily. Mammals harbor a protein named LACTB that shares sequence similarity with bacterial penicillin-binding proteins and β-lactamases. Since eukaryotes lack the synthesis machinery for peptidoglycan, the physiological role of LACTB is intriguing. Recently, LACTB has been validated in vivo to be causative for obesity, suggesting that LACTB is implicated in metabolic processes. The aim of this study was to investigate the phylogeny, structure, biochemistry and cell biology of LACTB in order to elucidate its physiological function. Phylogenetic analysis revealed that LACTB has evolved from penicillin binding-proteins present in the bacterial periplasmic space. A structural model of LACTB indicates that LACTB shares characteristic features common to all penicillin-binding proteins and β-lactamases. Recombinat LACTB protein expressed in E. coli was recovered in significant quantities. Biochemical and cell biology studies showed that LACTB is a soluble protein localized in the mitochondrial intermembrane space. Further analysis showed that LACTB preprotein underwent proteolytic processing disclosing an N-terminal tetrapeptide motif also found in a set of cell death-inducing proteins. Electron microscopy structural studies revealed that LACTB can polymerize to form stable filaments with lengths ranging from twenty to several hundred nanometers. These data suggest that LACTB filaments define a distinct microdomain in the intermembrane space. A possible role of LACTB filaments is proposed in the intramitochondrial membrane organization and microcompartmentation. The implications of these findings offer novel insight into the evolution of mitochondria. Further studies of the LACTB function might provide a tool to treat mitochondria-related metabolic diseases.

Quantum Space-Time and Noncommutative Gauge Field Theories

Arguments arising from quantum mechanics and gravitation theory as well as from string theory, indicate that the description of space-time as a continuous manifold is not adequate at very short distances. An important candidate for the description of space-time at such scales is provided by noncommutative space-time where the coordinates are promoted to noncommuting operators. Thus, the study of quantum field theory in noncommutative space-time provides an interesting interface where ordinary field theoretic tools can be used to study the properties of quantum spacetime. The three original publications in this thesis encompass various aspects in the still developing area of noncommutative quantum field theory, ranging from fundamental concepts to model building. One of the key features of noncommutative space-time is the apparent loss of Lorentz invariance that has been addressed in different ways in the literature. One recently developed approach is to eliminate the Lorentz violating effects by integrating over the parameter of noncommutativity. Fundamental properties of such theories are investigated in this thesis. Another issue addressed is model building, which is difficult in the noncommutative setting due to severe restrictions on the possible gauge symmetries imposed by the noncommutativity of the space-time. Possible ways to relieve these restrictions are investigated and applied and a noncommutative version of the Minimal Supersymmetric Standard Model is presented. While putting the results obtained in the three original publications into their proper context, the introductory part of this thesis aims to provide an overview of the present situation in the field.

Sensemaking in the Third Space - Essays on French-Finnish Bicultural Experiences in Organizations and Their Narratives (summary section only)

Research on cross-cultural and intercultural aspects in organizations has been traditionally conducted from an objectivist, functionalist perspective, with culture treated as an independent variable, and often the key explanatory factor. In order to do justice to the ontological relativity of the phenomena studied, more subjectivist research on intercultural interactions, and especially on their relationships with the dynamics of cultural identity construction, is needed. The present research seeks to address this gap by focusing on bicultural interactions in organizations, as they are experienced by the involved individuals. It is argued that such bicultural situations see the emergence of a space of hybridity, which is here called a ‘third space’, and which can be understood as providing ‘occasions for sensemaking’: it is this individual sensemaking that is of particular interest in the empirical narrative study. A first overall aim of the study is to reach an understanding of the dynamics of bicultural interactions in organizations; an understanding not only of the potential for learning and emancipatory sensemaking, but also of the possibility of conflict and alienatory ordering (this is mainly addressed in the theoretical essays 1 and 2). Further, a second overall aim of the study is to analyze the reflexive identity construction of four young French expatriates involved in such bicultural interactions in organizations in Finland, in order to examine the extent to which their expatriation experiences have allowed for an emancipatory opportunity in their cases (in essays 3 and 4). The primary theoretical contribution in this study lies in its new articulation of the dynamics of bicultural interactions in organizations. The ways in which the empirical material is analyzed bring about methodological contributions: since the expatriates’ accounts are bound to be some kind of construction, the analysis is made from angles that point to how the self-narratives construct reality. There are two such angles here: a ‘performative’ one and a ‘spatial’ one. The most important empirical contributions lie in the analysis of, on the one hand, the alternative uses that the young expatriates made of the notion of ‘national culture’ in their self-narratives, and, on the other hand, their ‘narrative practices of the third space’: their politics of escape or stabilization, their exploration of space or search for place, their emancipation from their origin or return to home as only horizon.

Gauge Field Theories, Quantum Space-Time and Some Applications

In this thesis, the possibility of extending the Quantization Condition of Dirac for Magnetic Monopoles to noncommutative space-time is investigated. The three publications that this thesis is based on are all in direct link to this investigation. Noncommutative solitons have been found within certain noncommutative field theories, but it is not known whether they possesses only topological charge or also magnetic charge. This is a consequence of that the noncommutative topological charge need not coincide with the noncommutative magnetic charge, although they are equivalent in the commutative context. The aim of this work is to begin to fill this gap of knowledge. The method of investigation is perturbative and leaves open the question of whether a nonperturbative source for the magnetic monopole can be constructed, although some aspects of such a generalization are indicated. The main result is that while the noncommutative Aharonov-Bohm effect can be formulated in a gauge invariant way, the quantization condition of Dirac is not satisfied in the case of a perturbative source for the point-like magnetic monopole.

Social networks for volunteered geographic information - A case study of OpenStreetMap

The world of mapping has changed. Earlier, only professional experts were responsible for map production, but today ordinary people without any training or experience can become map-makers. The number of online mapping sites, and the number of volunteer mappers has increased significantly. The development of the technology, such as satellite navigation systems, Web 2.0, broadband Internet connections, and smartphones, have had one of the key roles in enabling the rise of volunteered geographic information (VGI). As opening governmental data to public is a current topic in many countries, the opening of high quality geographical data has a central role in this study. The aim of this study is to investigate how is the quality of spatial data produced by volunteers by comparing it with the map data produced by public authorities, to follow what occurs when spatial data are opened for users, and to get acquainted with the user profile of these volunteer mappers. A central part of this study is OpenStreetMap project (OSM), which aim is to create a map of the entire world by volunteers. Anyone can become an OpenStreetMap contributor, and the data created by the volunteers are free to use for anyone without restricting copyrights or license charges. In this study OpenStreetMap is investigated from two viewpoints. In the first part of the study, the aim was to investigate the quality of volunteered geographic information. A pilot project was implemented by following what occurs when a high-resolution aerial imagery is released freely to the OpenStreetMap contributors. The quality of VGI was investigated by comparing the OSM datasets with the map data of The National Land Survey of Finland (NLS). The quality of OpenStreetMap data was investigated by inspecting the positional accuracy and the completeness of the road datasets, as well as the differences in the attribute datasets between the studied datasets. Also the OSM community was under analysis and the development of the map data of OpenStreetMap was investigated by visual analysis. The aim of the second part of the study was to analyse the user profile of OpenStreetMap contributors, and to investigate how the contributors act when collecting data and editing OpenStreetMap. The aim was also to investigate what motivates users to map and how is the quality of volunteered geographic information envisaged. The second part of the study was implemented by conducting a web inquiry to the OpenStreetMap contributors. The results of the study show that the quality of OpenStreetMap data compared with the data of National Land Survey of Finland can be defined as good. OpenStreetMap differs from the map of National Land Survey especially because of the amount of uncertainty, for example because of the completeness and uniformity of the map are not known. The results of the study reveal that opening spatial data increased notably the amount of the data in the study area, and both the positional accuracy and completeness improved significantly. The study confirms the earlier arguments that only few contributors have created the majority of the data in OpenStreetMap. The inquiry made for the OpenStreetMap users revealed that the data are most often collected by foot or by bicycle using GPS device, or by editing the map with the help of aerial imageries. According to the responses, the users take part to the OpenStreetMap project because they want to make maps better, and want to produce maps, which have information that is up-to-date and cannot be found from any other maps. Almost all of the users exploit the maps by themselves, most popular methods being downloading the map into a navigator or into a mobile device. The users regard the quality of OpenStreetMap as good, especially because of the up-to-dateness and the accuracy of the map.

Imagining Some Space

Some texts and a performance story. All motivated by the author’s interest in space, in this that surrounds, and that interest, in turn, originating from the author’s earlier studies in cultural anthropology, in observing and experiencing the surrounding animate and inanimate world. The texts in this thesis are alternating between academic and creative writing. They are texts written on a specific site on Suomenlinna island in Helsinki, Finland, as part of the performance ”Beyond the Wind in Front of Me / A Space Ship Journey” story or prologues to that, and the more academic ones supporting them or growing out of them, being accompanied also by the thoughts and practices of others. The main research questions and themes being How to perceive this that surrounds me? What is space, what does it consist of? Is it something that simply surrounds me? Am I a part of it or is it a part of me? How can a space be researched? How to activate a space? What kind of mental images do spaces/places create/uncover/open up in us? How to animate/make alive those images? Body giving meaning to space via actions created by the body. Physical environment contra emotional, imaginary, visionary one. Presence in a space/place. Physical and mental presence. Presence in memories.