Molecular Evolution of Metazoan Hypoxia-inducing Factors

Most metazoans rely on aerobic energy production, which is dependent on adequate oxygen supply. In the case of reduced oxygen supply (hypoxia), the most profound changes in gene expression are mediated by transcription factors named hypoxia-inducible factors (HIF alpha). These proteins are post-translationally regulated by prolyl-4-hydroxylase (PHD) enzymes that are direct “sensors” of cellular oxygen levels. This thesis examines the molecular evolution of metazoan HIF systems. In early metazoans the HIF system emerged from pre-existing PHD oxygen sensors and early bHLH-PAS transcription factors. In invertebrates our analysis revealed an unexpected diversity of PHD genes and HIF alpha sequence characteristics. An early branching vertebrate, the epaulette shark (Hemiscyllium ocellatum) was chosen for sequencing and hypoxia preconditioning studies of HIF alpha and PHD genes. As no quantitative PCR reference genes were available, this thesis includes the first study of reference genes in cartilaginous fish species. Applying multiple statistical analysis we also discoveredthat commonly used reference gene software may perform poorly with some data sets. Novel reference genes allowed accurate measurements of the mRNAlevels of the studied target genes. Cartilaginous fishes have three genomic duplicates of both HIF alpha and PHD genes like mammals and teleost fishes. Combining functional divergence and selection analyses it was possible to describe how sequence changes in both HIF alpha and PHD duplicates may have contributed to the differential oxygen sensitivityof HIF alphas. Additionally, novel teleost HIF-1 alpha sequences were produced and used to reveal the molecular evolution of HIF-1 alpha in this lineage rich with hypoxia tolerant species.

Contextualizing entrepreneurial intentions : a multiple case study on entrepreneurial cognition and perception

Avhandlingen behandlar entreprenöriella intentioner och individens uppfattningar om entreprenörskap. Om vi vill främja entreprenörskap så räcker det inte att vi förstår vilken nytta samhället kan ha av entreprenörer (arbetsplatser, mera skatteinkomster osv.). Vi måste förstå varför entreprenörskap är intressant och attraktiv ur individens synvinkel. Just den frågan har varit central inom kognitiv entreprenörskapsforskning de senaste 10 åren har vår förståelse för entreprenörer ökat betydligt tack vare den forskningen. Problemet med existerande forskning är att uppfattad genomförbarhet och uppfattad attraktivitet, dvs. de attityder som sägs leda till entreprenöriella intentioner, beskriver enbart vilken attityd individen generellt har till entreprenörskap. Enligt tidigare forskningsresultat så är det skillnad på generella attityder till en handling och attityder till att genomföra just den handlingen. Vill vi veta om individen kan tänka sig starta och driva ett företag så måste vi alltså studera individens attityd till att utföra just den specifika handlingen. Enligt avhandlingens forskningsresultat så kan vi lära oss mera om attityder till entreprenörskap genom att studera också motivation och mål. På så sätt kan vi förstå varför en del väljer att bli entreprenörer medan andra väljer att låta bli, även om de utåt sett har samma möjligheter att bli entreprenörer.

Autologous Stem Cell Transplantation In Multiple Myeloma

Background. Multiple myeloma (MM) is the second most common hematologic malignancy after lymphomas In Finland: the annual incidence of MM is approximately 200. For three decades the median survival remained at 3 to 4 years from diagnosis until high-dose melphalan treatment supported by autologous stem cell transplantation (ASCT) became the standard of care for newly diagnosed MM since the mid 1990’s and the median survival increased to 5 – 6 years. This study focuses on three important aspects of ASCT, namely 1) stem cell mobilization, 2) single vs. double ASCT as initial treatment, and 3) the role of minimal residual disease (MRD) for longterm outcome. Aim. The aim of this series of studies was to evaluate the outcomes of MM patients and the ASCT procedure at the Turku University Central Hospital, Finland. First, we tried to identify which factors predict unsuccessful mobilization of autologous stem cells. Second, we compared the use of short-acting granulocyte-colony stimulating factor (GCSF) with long-acting G-CSF as mobilization agents. Third, one and two successive ASCTs were compared in 100 patients with MM. Fourth, for patients in complete response (CR) after stem cell transplantation (SCT), patient-specific probes for quantitative allele-specific oligonucleotide polymerase-chain reaction (qASO-PCR) measurements were designed to evaluate MRD and its importance for long-term outcome. Results. The quantity of previous chemotherapy and previous interferon use were significant pre-mobilization factors that predicted mobilization failure, together with some factors related to mobilization therapy itself, such as duration and degree of cytopenias and occurrence of sepsis. Short-acting and long-acting G-CSF combined with chemotherapy were comparable as stem cells mobilizers. The progression free (PFS) and overall survival (OS) tended to be longer after double ASCT than after single ASCT with a median follow-up time of 4 years, but this difference disappeared as the follow-up time increased. qASO-PCR was a good and sensitive divider of the CR patients into two prognostic groups: MRD low/negative (≤ 0.01%) and MRD high (>0.01%) groups with a significant difference in PFS and suggestively also in OS. Conclusions. When the factors prediciting a poor outcome of stem cell mobilization prevail, it is possible to identify those patients who need specific efforts to maximize the mobilization efficacy. Long-acting pegfilgrastim is a practical and effective alternative to short-acting filgrastim for mobilization therapy. There is no need to perform double ASCT on all eligible patients. MRD assessment with qASO-PCR is a sensitive method for evaluation of the depth of the CR response and can be used to predict long-term outcome after ACST.

Comparison and Evaluation of Eddy Current Sensors

In the work eddy current sensors are described and evaluated. Theoretical part includes physical basics of the eddy currents, overview of available commercial products and technologies. Industrial sensors operation was assessed based on several working modes. Apart from this, the model was created in Matlab Simulink with Xilinx Blockset and then translated into a Xilinx ISE Design Suite compatible project. The performance of the resulting implementation was compared to the existing implementation in the Xilinx Spartan 3 FPGA board with the custom made sensor. Additionally, an introduction to FPGAs and VHDL is presented.

Comparative analysis of different meat traceability systems using multiple criteria and a social network approach

The adoption of a proper traceability system is being incorporated into meat production practices as a method of gaining consumer confidence. The various partners operating in the chain of meat production can be considered a social network, and they have the common goal of generating a communication process that can ensure each characteristic of the product, including safety. This study aimed to select the most appropriate meat traceability system “from farm to fork” that could be applied to Brazilian beef and pork production for international trade. The research was done in three steps. The first used the analytical hierarchy process (AHP) for selecting the best on-farm livestock traceability. In the second step, the actors in the meat production chain were identified to build a framework and defined each role in the network. In the third step, the selection of the traceability system was done. Results indicated that with an electronic traceability system, it is possible to acquire better connections between the links in the chain and to provide the means for managing uncertainties by creating structures that facilitate information flow more efficiently.

Tactile-Proprioceptive Robotic Grasping

Robotic grasping has been studied increasingly for a few decades. While progress has been made in this field, robotic hands are still nowhere near the capability of human hands. However, in the past few years, the increase in computational power and the availability of commercial tactile sensors have made it easier to develop techniques that exploit the feedback from the hand itself, the sense of touch. The focus of this thesis lies in the use of this sense. The work described in this thesis focuses on robotic grasping from two different viewpoints: robotic systems and data-driven grasping. The robotic systems viewpoint describes a complete architecture for the act of grasping and, to a lesser extent, more general manipulation. Two central claims that the architecture was designed for are hardware independence and the use of sensors during grasping. These properties enables the use of multiple different robotic platforms within the architecture. Secondly, new data-driven methods are proposed that can be incorporated into the grasping process. The first of these methods is a novel way of learning grasp stability from the tactile and haptic feedback of the hand instead of analytically solving the stability from a set of known contacts between the hand and the object. By learning from the data directly, there is no need to know the properties of the hand, such as kinematics, enabling the method to be utilized with complex hands. The second novel method, probabilistic grasping, combines the fields of tactile exploration and grasp planning. By employing well-known statistical methods and pre-existing knowledge of an object, object properties, such as pose, can be inferred with related uncertainty. This uncertainty is utilized by a grasp planning process which plans for stable grasps under the inferred uncertainty.

SOCIAL MEDIA IN INTERNATIONAL BRAND COMMUNICATION OF SMES - A multiple case study of small Finnish design-intensive companies

Social media is a rather new phenomenon which has revolutionised the world of online communication. However, academic research on how companies can benefit from social media is lacking. The research objective of this thesis was to examine the use of social media in international brand communication of small Finnish design-intensive companies. Therefore, this research contributes also to the research gap in SME branding. The focus was on communication targeted at consumers. The research was carried out as a mixed methods research employing the questionnaire and multiple case study methods. The questionnaire was used to gather preliminary information on Finnish design-intensive companies and to provide an eligible list of companies for deeper examination. Then, four case companies were studied in more depth. The empirical evidence of the case companies was mainly gathered through theme interviews. The results of the questionnaire shed light on the internationalisation of small Finnish designintensive companies. On average, the companies had internationalised rather quickly after they had been founded. However, the share of exports was rather low in most of the companies. The results revealed also that social media was already used widely in the exporting companies and the use can be expected to grow in future. The findings of the multiple case study suggest that branding activities in small Finnish designintensive companies are constrained by limited resources and skills. In addition, the branding activities are strongly guided by the vision and values of the entrepreneur(s) rather than extensive marketing research. The brand structure was simple in all case companies and they aimed at having a standardised brand image across markets. However, all case companies had faced a need for some adaptation of their international brand communication. Internationally important brand communication channels were international fairs, the internet, word-of-mouth and social media. Social media offered a cost-effective brand communication channel for the case companies. It was used for various purposes, such as creating brand awareness and affecting how the brand is perceived. The entrepreneurs found the use of social media to be rather easy and the case companies had not faced any major challenges. However, the companies had recognised that communication in social media requires consistency and planning. The planning was rather informal and stayed on a general level. Overall, the utilisation of social media in the case companies was limited by a lack of resources. It seemed to affect especially the follow-up of brand communication in social media which stayed rather superficial.

AMB system for high-speed motors using automatic commissioning

The general trend towards increasing e ciency and energy density drives the industry to high-speed technologies. Active Magnetic Bearings (AMBs) are one of the technologies that allow contactless support of a rotating body. Theoretically, there are no limitations on the rotational speed. The absence of friction, low maintenance cost, micrometer precision, and programmable sti ness have made AMBs a viable choice for highdemanding applications. Along with the advances in power electronics, such as signi cantly improved reliability and cost, AMB systems have gained a wide adoption in the industry. The AMB system is a complex, open-loop unstable system with multiple inputs and outputs. For normal operation, such a system requires a feedback control. To meet the high demands for performance and robustness, model-based control techniques should be applied. These techniques require an accurate plant model description and uncertainty estimations. The advanced control methods require more e ort at the commissioning stage. In this work, a methodology is developed for an automatic commissioning of a subcritical, rigid gas blower machine. The commissioning process includes open-loop tuning of separate parts such as sensors and actuators. The next step is to apply a system identi cation procedure to obtain a model for the controller synthesis. Finally, a robust model-based controller is synthesized and experimentally evaluated in the full operating range of the system. The commissioning procedure is developed by applying only the system components available and a priori knowledge without any additional hardware. Thus, the work provides an intelligent system with a self-diagnostics feature and an automatic commissioning.

Do induced twin pregnancies influence the obstetric and neonatal results of multiple births born before 32 weeks? Comparison to spontaneous gestation

PURPOSE: To compare obstetric outcomes of induced preterm twin births (under 32 weeks gestation) with those spontaneously conceived. METHODS: Prospective study of twin pregnancies (25 induced and 157 spontaneously conceived) developed over a period of 16 years in a tertiary obstetric center. Demographic factors, obstetric complications, gestational age at delivery, mode of delivery, birth weight and immediate newborn outcome were compared. RESULTS: The analysis of obstetrical complications concerning urinary or other infections, hypertensive disorders of pregnancy, gestational diabetes, fetal malformations, intrauterine fetal death, intrauterine growth restriction and intrauterine discordant growth reveal no significant statistical differences between the two groups. First trimester bleeding was higher in the induced group (24 versus 8.3%, p=0.029). The cesarean delivery rate was 52.2% in spontaneous gestations and 64% in induced gestations. Gestational age at delivery, birth weight, Apgar scores at first and fifth minutes, admissions to Neonatal Intensive Care Unit and puerperal complications show no statistically significant differences between the two groups. These results were independent of chorionicity and induction method. CONCLUSION: The mode of conception did not influence obstetric and neonatal outcomes. Although induced pregnancies have higher risk of first trimester bleeding, significant differences were not observed regarding other obstetric and puerperal complications and neonatal results.

Magnetic Resocance Imaging Methods in the Follow-up of Multiple Sclerosis and in Farby Disease

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system. MS is the most common disabling central nervous system (CNS) disease of young adults in the Western world. In Finland, the prevalence of MS ranges between 1/1000 and 2/1000 in different areas. Fabry disease (FD) is a rare hereditary metabolic disease due to mutation in a single gene coding α-galactosidase A (alpha-gal A) enzyme. It leads to multi-organ pathology, including cerebrovascular disease. Currently there are 44 patients with diagnosed FD in Finland. Magnetic resonance imaging (MRI) is commonly used in the diagnostics and follow-up of these diseases. The disease activity can be demonstrated by occurrence of new or Gadolinium (Gd)-enhancing lesions in routine studies. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are advanced MR sequences which can reveal pathologies in brain regions which appear normal on conventional MR images in several CNS diseases. The main focus in this study was to reveal whether whole brain apparent diffusion coefficient (ADC) analysis can be used to demonstrate MS disease activity. MS patients were investigated before and after delivery and before and after initiation of diseasemodifying treatment (DMT). In FD, DTI was used to reveal possible microstructural alterations at early timepoints when excessive signs of cerebrovascular disease are not yet visible in conventional MR sequences. Our clinical and MRI findings at 1.5T indicated that post-partum activation of the disease is an early and common phenomenon amongst mothers with MS. MRI seems to be a more sensitive method for assessing MS disease activity than the recording of relapses. However, whole brain ADC histogram analysis is of limited value in the follow-up of inflammatory conditions in a pregnancy-related setting because the pregnancy-related physiological effects on ADC overwhelm the alterations in ADC associated with MS pathology in brain tissue areas which appear normal on conventional MRI sequences. DTI reveals signs of microstructural damage in brain white matter of FD patients before excessive white matter lesion load can be observed on conventional MR scans. DTI could offer a valuable tool for monitoring the possible effects of enzyme replacement therapy in FD.

Modelling of potentiometric ion sensors

Potentiometric ion sensors are a very important subgroup of electrochemical sensors, very attractive for practical applications due to their small size, portability, low-energy consumption, relatively low cost and not changing the sample composition. They are investigated by the researchers from many fields of science. The continuous development of this field creates the necessity for a detailed description of sensor response and the electrochemical processes important in the practical applications of ion sensors. The aim of this thesis is to present the existing models available for the description of potentiometric ion sensors as well as their applicability and limitations. This includes the description of the diffusion potential occurring at the reference electrodes. The wide range of existing models, from most idealised phase boundary models to most general models, including migration, is discussed. This work concentrates on the advanced modelling of ion sensors, namely the Nernst-Planck-Poisson (NPP) model, which is the most general of the presented models, therefore the most widely applicable. It allows the modelling of the transport processes occurring in ion sensors and generating the potentiometric response. Details of the solution of the NPP model (including the numerical methods used) are shown. The comparisons between NPP and the more idealized models are presented. The applicability of the model to describe the formation of diffusion potential in reference electrode, the lower detection limit of both ion-exchanger and neutral carrier electrodes and the effect of the complexation in the membrane are discussed. The model was applied for the description of both types of electrodes, i.e. with the inner filling solution and solidcontact electrodes. The NPP model allows the electrochemical methods other than potentiometry to be described. Application of this model in Electrochemical Impedance Spectroscopy is discussed and a possible use in chrono-potentiometry is indicated. By combining the NPP model with evolutionary algorithms, namely Hierarchical Genetic Strategy (HGS), a novel method allowing the facilitation of the design of ion sensors was created. It is described in detail in this thesis and its possible applications in the field of ion sensors are indicated. Finally, some interesting effects occurring in the ion sensors (i.e. overshot response and influence of anionic sites) as well as the possible applications of NPP in biochemistry are described.

Product placement on personal blogs: a multiple case study from companies’ perspective

As traditional advertising is losing its value in corporations’ marketing, new and growing social media marketing channels are increasing their importance. The growing interest in the media and the lack of research on the subject create a clear need for this study. The objectives are to increase understanding about product placement in personal blogs and examine the benefits as well as the downsides created by this marketing channel and present the requirements for success. The study also takes a stand on what kind of things a successful product placement strategy in personal blogs includes and what points should be considered when creating a strategy. The study’s empirical part consists of seven thematic interviews with case companies’ representatives and one agent. The study’s personal blogs were delimited to consist only lifestyle and fashion blogs. The results show that product placement on personal lifestyle and fashion blogs is a strongly growing marketing channel and it is best suited to reach young women. It is also a very good channel to change and improve brand image. Via personal blogs it is possible to reach a large number of consumers with a very cost-efficient manner. Thus utilizing the channel is suitable for all companies regardless of the size of the marketing budget. Of course, companies have to consider the suitability of their product to the themes of blogs. Executing a successful campaign in this media requires good relationship management skills and understanding of this particular media as the final content is not in advertiser’s hands. As a marketing channel, personal blogs differ highly from traditional marketing channels because of their constantly changing nature and multidirectional quality where several parties are in interaction.

Multiple scales analysis of nonlinear oscillations of a portal frame foundation for several machines

An analytical study of the nonlinear vibrations of a multiple machines portal frame foundation is presented. Two unbalanced rotating machines are considered, none of them resonant with the lower natural frequencies of the supporting structure. Their combined frequencies is set in such a way as to excite, due to nonlinear behavior of the frame, either the first anti-symmetrical mode (sway) or the first symmetrical mode. The physical and geometrical characteristics of the frame are chosen to tune the natural frequencies of these two modes into a 1:2 internal resonance. The problem is reduced to a two degrees of freedom model and its nonlinear equations of motions are derived via a Lagrangian approach. Asymptotic perturbation solutions of these equations are obtained via the Multiple Scales Method.

Characterization of capacitive sensors for measurements of the moisture in irrigated soils

The irrigation is a technique developed to supply the hydric needs of the plants. The use of the water should be optimized so that the culture just has enough for its growth, avoiding waste. The objective of this work was to characterize the behavior of capacitive sensors of humidity to monitor the moisture in the soils. In first instance, it was appraised sensors with dielectric built of synthetic pomes stone (Rd = 0,4 and Rd = 0,8) and of soil samples (Rd = 0,8 and Rd = 1,0), being the Rd parameter a geometric factor that relates the distance between the capacitor plates with radius of the plates. For the calibration, the sensors were installed in PVC recipient of cylindrical shape, filled with soil. The set (sensor and soil) was humidified by capillary effect and submitted by a natural drying very slowly. The parameter readings were taken daily, which allowed obtain the curves relating the humidity percentage, expressed in terms of dry weight, with the output voltage fort the sensor. The experiments were performed in sand soil and in dark red latossolo. The obtained results allowed to infer that the behavior of the sensor has a specific feature for each type of soil, being, therefore, necessary to develop a own calibration curve for the sensor, when used in soil with specific characteristic.