Performance analysis of software run-time behaviour using 3D-visualisation

Monimutkaisen tietokonejärjestelmän suorituskykyoptimointi edellyttää järjestelmän ajonaikaisen käyttäytymisen ymmärtämistä. Ohjelmiston koon ja monimutkaisuuden kasvun myötä suorituskykyoptimointi tulee yhä tärkeämmäksi osaksi tuotekehitysprosessia. Tehokkaampien prosessorien käytön myötä myös energiankulutus ja lämmöntuotto ovat nousseet yhä suuremmiksi ongelmiksi, erityisesti pienissä, kannettavissa laitteissa. Lämpö- ja energiaongelmien rajoittamiseksi on kehitetty suorituskyvyn skaalausmenetelmiä, jotka edelleen lisäävät järjestelmän kompleksisuutta ja suorituskykyoptimoinnin tarvetta. Tässä työssä kehitettiin visualisointi- ja analysointityökalu ajonaikaisen käyttäytymisen ymmärtämisen helpottamiseksi. Lisäksi kehitettiin suorituskyvyn mitta, joka mahdollistaa erilaisten skaalausmenetelmien vertailun ja arvioimisen suoritusympäristöstä riippumatta, perustuen joko suoritustallenteen tai teoreettiseen analyysiin. Työkalu esittää ajonaikaisesti kerätyn tallenteen helposti ymmärrettävällä tavalla. Se näyttää mm. prosessit, prosessorikuorman, skaalausmenetelmien toiminnan sekä energiankulutuksen kolmiulotteista grafiikkaa käyttäen. Työkalu tuottaa myös käyttäjän valitsemasta osasta suorituskuvaa numeerista tietoa, joka sisältää useita oleellisia suorituskykyarvoja ja tilastotietoa. Työkalun sovellettavuutta tarkasteltiin todellisesta laitteesta saatua suoritustallennetta sekä suorituskyvyn skaalauksen simulointia analysoimalla. Skaalausmekanismin parametrien vaikutus simuloidun laitteen suorituskykyyn analysoitiin.

Linea omnes dati generis determinato sub angulo secans in spatio trium dimensionum investigans

Dedikaatio: Fredrika Wilhelmina Stjernvall född Charpentier [ruots.].

Impingement jet cooling of end windings in a high-speed electric machine

The rotational speed of high-speed electric machines is over 15 000 rpm. These machines are compact in size when compared to the power rate. As a consequence, the heat fluxes are at a high level and the adequacy of cooling becomes an important design criterion. In the high-speed machines, the air gap between the stator and rotor is a narrow flow channel. The cooling air is produced with a fan and the flow is then directed to the air gap. The flow in the gap does not provide sufficient cooling for the stator end windings, and therefore additional cooling is required. This study investigates the heat transfer and flow fields around the coil end windings when cooling jets are used. As a result, an innovative and new assembly is introduced for the cooling jets, with the benefits of a reduced amount of hot spots, a lower pressure drop, and hence a lower power need for the cooling fan. The gained information can also be applied to improve the cooling of electric machines through geometry modifications. The objective of the research is to determine the locations of the hot spots and to find out induced pressure losses with different jet alternatives. Several possibilities to arrange the extra cooling are considered. In the suggested approach cooling is provided by using a row of air jets. The air jets have three main tasks: to cool the coils effectively by direct impingement jets, to increase and cool down the flow that enters the coil end space through the air gap, and to ensure the correct distribution of the flow by forming an air curtain with additional jets. One important aim of this study is the arrangement of cooling jets in such manner that hot spots can be avoided to wide extent. This enables higher power density in high-speed motors. This cooling system can also be applied to the ordinary electric machines when efficient cooling is needed. The numerical calculations have been performed using a commercial Computational Fluid Dynamics software. Two geometries have been generated: cylindrical for the studied machine and Cartesian for the experimental model. The main parameters include the positions, arrangements and number of jets, the jet diameters, and the jet velocities. The investigated cases have been tested with two widely used turbulence models and using a computational grid of over 500 000 cells. The experimental tests have been made by using a simplified model for the end winding space with cooling jets. In the experiments, an emphasis has been given to flow visualisation. The computational analysis shows good agreement with the experimental results. Modelling of the cooling jet arrangement enables also a better understanding of the complex system of heat transfer at end winding space.

Imaging techniques applied for detection of secretion, transgene delivery and G proteincoupled receptors in reproductive and endocrine cells in vivo and in vitro

Post-testicular sperm maturation occurs in the epididymis. The ion concentration and proteins secreted into the epididymal lumen, together with testicular factors, are believed to be responsible for the maturation of spermatozoa. Disruption of the maturation of spermatozoa in the epididymis provides a promising strategy for generating a male contraceptive. However, little is known about the proteins involved. For drug development, it is also essential to have tools to study the function of these proteins in vitro. One approach for screening novel targets is to study the secretory products of the epididymis or the G protein-coupled receptors (GPCRs) that are involved in the maturation process of the spermatozoa. The modified Ca2+ imaging technique to monitor release from PC12 pheochromocytoma cells can also be applied to monitor secretory products involved in the maturational processes of spermatozoa. PC12 pheochromocytoma cells were chosen for evaluation of this technique as they release catecholamines from their cell body, thus behaving like endocrine secretory cells. The results of the study demonstrate that depolarisation of nerve growth factor -differentiated PC12 cells releases factors which activate nearby randomly distributed HEL erythroleukemia cells. Thus, during the release process, the ligands reach concentrations high enough to activate receptors even in cells some distance from the release site. This suggests that communication between randomly dispersed cells is possible even if the actual quantities of transmitter released are extremely small. The development of a novel method to analyse GPCR-dependent Ca2+ signalling in living slices of mouse caput epididymis is an additional tool for screening for drug targets. By this technique it was possible to analyse functional GPCRs in the epithelial cells of the ductus epididymis. The results revealed that, both P2X- and P2Y-type purinergic receptors are responsible for the rapid and transient Ca2+ signal detected in the epithelial cells of caput epididymides. Immunohistochemical and reverse transcriptase-polymerase chain reaction (RTPCR) analyses showed the expression of at least P2X1, P2X2, P2X4 and P2X7, and P2Y1 and P2Y2 receptors in the epididymis. Searching for epididymis-specific promoters for transgene delivery into the epididymis is of key importance for the development of specific models for drug development. We used EGFP as the reporter gene to identify proper promoters to deliver transgenes into the epithelial cells of the mouse epididymis in vivo. Our results revealed that the 5.0 kb murine Glutathione peroxidase 5 (GPX5) promoter can be used to target transgene expression into the epididymis while the 3.8 kb Cysteine-rich secretory protein-1 (CRISP-1) promoter can be used to target transgene expression into the testis. Although the visualisation of EGFP in living cells in culture usually poses few problems, the detection of EGFP in tissue sections can be more difficult because soluble EGFP molecules can be lost if the cell membrane is damaged by freezing, sectioning, or permeabilisation. Furthermore, the fluorescence of EGFP is dependent on its conformation. Therefore, fixation protocols that immobilise EGFP may also destroy its usefulness as a fluorescent reporter. We therefore developed a novel tissue preparation and preservation techniques for EGFP. In addition, fluorescence spectrophotometry with epididymal epithelial cells in suspension revealed the expression of functional purinergic, adrenergic, cholinergic and bradykinin receptors in these cell lines (mE-Cap27 and mE-Cap28). In conclusion, we developed new tools for studying the role of the epididymis in sperm maturation. We developed a new technique to analyse GPCR dependent Ca2+ signalling in living slices of mouse caput epididymis. In addition, we improved the method of detecting reporter gene expression. Furthermore, we characterised two epididymis-specific gene promoters, analysed the expression of GPCRs in epididymal epithelial cells and developed a novel technique for measurement of secretion from cells.

Mitä jos... -musiikkivideon suunnittelu ja toteutus

Opinnäytetyössä tarkastellaan ensikertalaisen tekemää musiikkivideoprojektia ammattilaisten musiikkivideon tekemiseen. Toimin teososassa käsikirjoittajana, ohjaajana ja tuottajana. Työssä kerrotaan musiikkivideon historiasta ja kehityksestä maailmalla ja Suomessa lyhyesti. Käydään koko musiikkivideon tuotantokaari kappaleen valinnasta, käsikirjoituksesta, kuvakerronnan suunnittelusta, työryhmän ja esiintyjien valitsemisesta aina kuvauspäiviin ja jälkikäsittelyyn. Jokaista eri tuotantovaihetta verrataan ammattilaisten musiikkivideon tekemiseen. Pohditaan, miten saatiin tehtyä koko tuotantokaaren osa-alueet ammattimaisesti, vaikka budjetin olemattomuus asetti haasteita prosessin tekemiselle. Musiikkivideon tarkoitus on promotoida artistia tai yhtyettä ja luoda heille jonkinlainen imago. Artistin tyylin ratkaisee lähinnä musiikki, jollaista hän esittää. Työ vertailee erilaisia musiikkivideotyylejä ja pohtii, miksi kyseisessä musiikkivideossa oli valittu juuri tarinallinen tyyli. Tutkitaan myös miten kuvaussuunnittelu onnistui musiikkivideon tarinan näkökulmasta. Vaihe vaiheelta käydään läpi kuvauspäivien tapahtumat. Kerrotaan, millaisia ongelmia prosessi tuotti ja miten ne saatiin ratkaistua. - Opinnäytetyössä on liitteenä musiikkivideon käsikirjoitus, kuvausaikataulu ja osa kuvakäsikirjoituksesta. - Opinnäytetyöhön kuuluu teososa, musiikkivideo Mitä jos...

The impact of bioavailability limitations on microbial stable isotope fractionation in a multiphase system

Stable isotope fractionation analysis of contaminants is a promising method for assessing biodegradation of contaminants in natural systems. However, standard procedures to determine stable isotope fractionation factors, so far, neglect the influence of pollutant bioavailability on stable isotope fractionation. On a microscale, bioavailability may vary due to the spatio-temporal variability of local contaminant concentrations, limited effective diffusivities of the contaminants and cell densities, and thus, the pollutant supply might not meet the intrinsic degradation capacity of the microorganisms. The aim of this study was to demonstrate the effect of bioavailability on the apparent stable isotope fractionation, using a multiphase laboratory setup. The data gained show that the apparent isotope fractionation factors observed during biodegradation processes depend on the amount of biomass and/or the rate of toluene mass transfer from a second to the aqueous phase. They indicate that physico-chemical processes need to be taken into account when stable isotope fractionation analysis is used for the quantification of environmental contaminant degradation.

Factors Regulating Chondrogenic Differentiation

Chondrogenesis is a co-ordinated differentiation process in which mesenchymal cells condensate, differentiate into chondrocytes and begin to secrete molecules that form the extracellular matrix. It is regulated in a spatio-temporal manner by cellular interactions and growth and differentiation factors that modulate cellular signalling pathways and transcription of specific genes. Moreover, post-transcriptional regulation by microRNAs (miRNAs) has appeared to play a central role in diverse biological processes, but their role in skeletal development is not fully understood. Mesenchymal stromal cells (MSCs) are multipotent cells present in a variety of adult tissues, including bone marrow and adipose tissue. They can be isolated, expanded and, under defined conditions, induced to differentiate into multiple cell lineages including chondrocytes, osteoblasts and adipocytes in vitro and in vivo. Owing to their intrinsic capability to self-renew and differentiate into functional cell types, MSCs provide a promising source for cell-based therapeutic strategies for various degenerative diseases, such as osteoarthritis (OA). Due to the potential therapeutic applications, it is of importance to better understand the MSC biology and the regulatory mechanisms of their differentiation. In this study, an in vitro assay for chondrogenic differentiation of mouse MSCs (mMSCs) was developed for the screening of various factors for their chondrogenic potential. Conditions were optimized for pellet cultures by inducing mMSC with different bone morphogenetic proteins (BMPs) that were selected based on their known chondrogenic relevance. Characterization of the surface epitope profile, differentiation capacity and molecular signature of mMSCs illustrated the importance of cell population composition and the interaction between different populations in the cell fate determination and differentiation of MSCs. Regulation of Wnt signalling activity by Wnt antagonist sFRP-1 was elucidated as a potential modulator of lineage commitment. Delta-like 1 (dlk1), a factor regulating adipogenesis and osteogenesis, was shown to exhibit stage-specific expression during embryonic chondrogenesis and identified as a novel regulator of chondrogenesis, possibly through mediating the effect of TGF-beta1. Moreover, miRNA profiling demonstrated that MSCs differentiating into a certain lineage exhibit a specific miRNA expression profile. The complex regulatory network between miRNAs and transcription factors is suggested to play a crucial role in fine-tuning the differentiation of MSCs. These results demonstrate that commitment of mesenchymal stromal cells and further differentiation into specific lineages is regulated by interactions between MSCs, various growth and transcription factors, and miRNA-mediated translational repression of lineage-specific genes.

Parallella, dynamiska representationer i gymnasiefysiken : implementering av ett interaktivt datorverktyg i didaktiska situationer och uppfattning av effektivt lärande

The computer is a useful tool in the teaching of upper secondary school physics, and should not have a subordinate role in students' learning process. However, computers and computer-based tools are often not available when they could serve their purpose best in the ongoing teaching. Another problem is the fact that commercially available tools are not usable in the way the teacher wants. The aim of this thesis was to try out a novel teaching scenario in a complicated subject in physics, electrodynamics. The didactic engineering of the thesis consisted of developing a computer-based simulation and training material, implementing the tool in physics teaching and investigating its effectiveness in the learning process. The design-based research method, didactic engineering (Artigue, 1994), which is based on the theoryof didactical situations (Brousseau, 1997), was used as a frame of reference for the design of this type of teaching product. In designing the simulation tool a general spreadsheet program was used. The design was based on parallel, dynamic representations of the physics behind the function of an AC series circuit in both graphical and numerical form. The tool, which was furnished with possibilities to control the representations in an interactive way, was hypothesized to activate the students and promote the effectiveness of their learning. An effect variable was constructed in order to measure the students' and teachers' conceptions of learning effectiveness. The empirical study was twofold. Twelve physics students, who attended a course in electrodynamics in an upper secondary school, participated in a class experiment with the computer-based tool implemented in three modes of didactical situations: practice, concept introduction and assessment. The main goal of the didactical situations was to have students solve problems and study the function of AC series circuits, taking responsibility for theirown learning process. In the teacher study eighteen Swedish speaking physics teachers evaluated the didactic potential of the computer-based tool and the accompanying paper-based material without using them in their physics teaching. Quantitative and qualitative data were collected using questionnaires, observations and interviews. The result of the studies showed that both the group of students and the teachers had generally positive conceptions of learning effectiveness. The students' conceptions were more positive in the practice situation than in the concept introduction situation, a setting that was more explorative. However, it turned out that the students' conceptions were also positive in the more complex assessment situation. This had not been hypothesized. A deeper analysis of data from observations and interviews showed that one of the students in each pair was more active than the other, taking more initiative and more responsibilityfor the student-student and student-computer interaction. These active studentshad strong, positive conceptions of learning effectiveness in each of the threedidactical situations. The group of less active students had a weak but positive conception in the first iv two situations, but a negative conception in the assessment situation, thus corroborating the hypothesis ad hoc. The teacher study revealed that computers were seldom used in physics teaching and that computer programs were in short supply. The use of a computer was considered time-consuming. As long as physics teaching with computer-based tools has to take place in special computer rooms, the use of such tools will remain limited. The affordance is enhanced when the physical dimensions as well as the performance of the computer are optimised. As a consequence, the computer then becomes a real learning tool for each pair of students, smoothly integrated into the ongoing teaching in the same space where teaching normally takes place. With more interactive support from the teacher, the computer-based parallel, dynamic representations will be efficient in promoting the learning process of the students with focus on qualitative reasoning - an often neglected part of the learning process of the students in upper secondary school physics.

A Farewell to Flat Biology. Three-dimensional Cell Culture Models in Cancer Drug Target Identification and Validation

Cells of epithelial origin, e.g. from breast and prostate cancers, effectively differentiate into complex multicellular structures when cultured in three-dimensions (3D) instead of conventional two-dimensional (2D) adherent surfaces. The spectrum of different organotypic morphologies is highly dependent on the culture environment that can be either non-adherent or scaffold-based. When embedded in physiological extracellular matrices (ECMs), such as laminin-rich basement membrane extracts, normal epithelial cells differentiate into acinar spheroids reminiscent of glandular ductal structures. Transformed cancer cells, in contrast, typically fail to undergo acinar morphogenic patterns, forming poorly differentiated or invasive multicellular structures. The 3D cancer spheroids are widely accepted to better recapitulate various tumorigenic processes and drug responses. So far, however, 3D models have been employed predominantly in the Academia, whereas the pharmaceutical industry has yet to adopt a more widely and routine use. This is mainly due to poor characterisation of cell models, lack of standardised workflows and high throughput cell culture platforms, and the availability of proper readout and quantification tools. In this thesis, a complete workflow has been established entailing well-characterised 3D cell culture models for prostate cancer, a standardised 3D cell culture routine based on high-throughput-ready platform, automated image acquisition with concomitant morphometric image analysis, and data visualisation, in order to enable large-scale high-content screens. Our integrated suite of software and statistical analysis tools were optimised and validated using a comprehensive panel of prostate cancer cell lines and 3D models. The tools quantify multiple key cancer-relevant morphological features, ranging from cancer cell invasion through multicellular differentiation to growth, and detect dynamic changes both in morphology and function, such as cell death and apoptosis, in response to experimental perturbations including RNA interference and small molecule inhibitors. Our panel of cell lines included many non-transformed and most currently available classic prostate cancer cell lines, which were characterised for their morphogenetic properties in 3D laminin-rich ECM. The phenotypes and gene expression profiles were evaluated concerning their relevance for pre-clinical drug discovery, disease modelling and basic research. In addition, a spontaneous model for invasive transformation was discovered, displaying a highdegree of epithelial plasticity. This plasticity is mediated by an abundant bioactive serum lipid, lysophosphatidic acid (LPA), and its receptor LPAR1. The invasive transformation was caused by abrupt cytoskeletal rearrangement through impaired G protein alpha 12/13 and RhoA/ROCK, and mediated by upregulated adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A, and Rac/ PAK pathways. The spontaneous invasion model tangibly exemplifies the biological relevance of organotypic cell culture models. Overall, this thesis work underlines the power of novel morphometric screening tools in drug discovery.

The revival of international solidarity : the Internationale Arbeiterhilfe, Willi Münzenberg and the Comintern in Weimar Germany, 1921-1933

The aim of the study is to write the first comprehensive history of the Internationale Arbeiterhilfe (International Workers’ Relief) and its message of international solidarity during the Weimar Republic, 1921–1933. The Arbeiterhilfe was the Communist International’s (Comintern) primary international solidarity organisation of the time. The work is identified as a contribution to the transnational history of the interwar period as its main focus is not on governmental politics or intra-state relations, but is focused on the transnational world of an international organisation. The history of the Arbeiterhilfe provides the main springboard from which to write a contextually-based analysis of international solidarity during the Weimar Republic. The study highlights for the first time the importance of the German communist Willi Münzenberg (1889–1940), as the leader of the Arbeiterhilfe, in the history of international solidarity. The main question of this study is how an explicit use of language coupled with the visualisation and practices of solidarity were created through the Arbeiterhilfe. How was solidarity actually envisaged, organised and brought to life by the Arbeiterhilfe in Weimar Germany? How did its expressions of solidarity change over time? Throughout the thesis, the changing and complex character of solidarity is analysed. How was the Arbeiterhilfe’s message of solidarity created and changed in relation to the Comintern and the Soviet Union’s policies? How did the Arbeiterhilfe create a new culture of international solidarity thought film, cinema, illustrated newspapers and the organising of mass spectacles of international solidarity? The Arbeiterhilfe had its international headquarters in Berlin which functioned as the base, one could argue, for some of the inter-war period’s most spectacular solidarity campaigns. The Arbeiterhilfe constitutes a significant case study of an early international organisation as it was one of the first international organisations for global (albeit not universal) international solidarity which had unparalleled prospects to develop new transnational identifications and social ties. It could consequently be suggested that the Arbeiterhilfe in several ways could be perceived as a predecessor to several post-1945 transnational solidarity organisations and International Non-Governmental Organisations (INGOs).

Membrane properties of structurally modified ceramides : effects on lipid lateral distribution and sphingomyelin-interactions in artificial bilayer membranes

Ceramides comprise a class of sphingolipids that exist only in small amounts in cellular membranes, but which have been associated with important roles in cellular signaling processes. The influences that ceramides have on the physical properties of bilayer membranes reach from altered thermodynamical behavior to significant impacts on the molecular order and lateral distribution of membrane lipids. Along with the idea that the membrane physical state could influence the physiological state of a cell, the membrane properties of ceramides have gained increasing interest. Therefore, membrane phenomena related to ceramides have become a subject of intense study both in cellular as well as in artificial membranes. Artificial bilayers, the so called model membranes, are substantially simpler in terms of contents and spatio-temporal variation than actual cellular membranes, and can be used to give detailed information about the properties of individual lipid species in different environments. This thesis focuses on investigating how the different parts of the ceramide molecule, i.e., the N-linked acyl chain, the long-chain sphingoid base and the membrane-water interface region, govern the interactions and lateral distribution of these lipids in bilayer membranes. With the emphasis on ceramide/sphingomyelin(SM)-interactions, the relevance of the size of the SMhead group for the interaction was also studied. Ceramides with methylbranched N-linked acyl chains, varying length sphingoid bases, or methylated 2N (amide-nitrogen) and 3O (C3-hydroxyl) at the interface region, as well as SMs with decreased head group size, were synthesized and their bilayer properties studied by calorimetric and fluorescence spectroscopic techniques. In brief, the results showed that the packing of the ceramide acyl chains was more sensitive to methyl-branching in the mid part than in the distal end of the N-linked chain, and that disrupting the interfacial structure at the amide-nitrogen, as opposed to the C3-hydroxyl, had greater effect on the interlipid interactions of ceramides. Interestingly, it appeared that the bilayer properties of ceramides could be more sensitive to small alterations in the length of the long-chain base than what was previously reported for the N-linked acyl chain. Furthermore, the data indicated that the SM-head group does not strongly influence the interactions between SMs and ceramides. The results in this thesis illustrate the pivotal role of some essential parts of the ceramide molecules in determining their bilayer properties. The thesis provides increased understanding of the molecular aspects of ceramides that possibly affect their functions in biological membranes, and could relate to distinct effects on cell physiology.

Post-processing and analysis of tracked hand trajectories

In this thesis, the suitability of different trackers for finger tracking in high-speed videos was studied. Tracked finger trajectories from the videos were post-processed and analysed using various filtering and smoothing methods. Position derivatives of the trajectories, speed and acceleration were extracted for the purposes of hand motion analysis. Overall, two methods, Kernelized Correlation Filters and Spatio-Temporal Context Learning tracking, performed better than the others in the tests. Both achieved high accuracy for the selected high-speed videos and also allowed real-time processing, being able to process over 500 frames per second. In addition, the results showed that different filtering methods can be applied to produce more appropriate velocity and acceleration curves calculated from the tracking data. Local Regression filtering and Unscented Kalman Smoother gave the best results in the tests. Furthermore, the results show that tracking and filtering methods are suitable for high-speed hand-tracking and trajectory-data post-processing.