Pluripotency and genetic stability of human pluripotent stem cells

Pluripotent cells have the potential to differentiate into all somatic cell types. As the adult human body is unable to regenerate various tissues, pluripotent cells provide an attractive source for regenerative medicine. Human embryonic stem cells (hESCs) can be isolated from blastocyst stage embryos and cultured in the laboratory environment. However, their use in regenerative medicine is restricted due to problems with immunosuppression by the host and ethical legislation. Recently, a new source of pluripotent cells was established via the direct reprogramming of somatic cells. These human induced pluripotent stem cells (hiPSCs) enable the production of patient specific cell types. However, numerous challenges, such as efficient reprogramming, optimal culture, directed differentiation, genetic stability and tumor risk need to be solved before the launch of therapeutic applications. The main objective of this thesis was to understand the unique properties of human pluripotent stem cells. The specific aims were to identify novel factors involved in maintaining pluripotency, characterize the effects of low oxygen culture on hESCs, and determine the high resolution changes in hESCs and hiPSCs during culture and reprogramming. As a result, the previously uncharacterized protein L1TD1 was determined to be specific for pluripotent cells and essential for the maintenance of pluripotency. The low oxygen culture supported undifferentiated growth and affected expression of stem cell associated transcripts. High resolution screening of hESCs identified a number of culture induced copy number variations and loss of heterozygosity changes. Further, screening of hiPSCs revealed that reprogramming induces high resolution alterations. The results obtained in this thesis have important implications for stem cell and cancer biology and the therapeutic potential of pluripotent cells.

Applications and Benefits of Adaptive Pulsed GMAW

In ship and offshore terminal construction, welded cross sections are thick and the number of welds very high. Consequently, there are two aspects of great importance; cost and heat input. Reduction in the welding operation time decreases the costs of the work force and avoids excessive heat, preventing distortion and other weld defects. The need to increase productivity while using a single wire in the GMAW process has led to the use of a high current and voltage to improve the melting rate. Unfortunately, this also increases the heat input. Innovative GMAW processes, mostly implemented for sheet plate sections, have shown significant reduction in heat input (Q), low distortion and increase in welding speed. The aim of this study is to investigate adaptive pulsed GMAW processes and assess relevant applications in the high power range, considering possible benefits when welding thicker sections and high yield strength steel. The study experimentally tests the usability of adaptive welding processes and evaluates their effects on weld properties, penetration and shapes of the weld bead.The study first briefly reviews adaptive GMAW to evaluate different approaches and their applications and to identify benefits in adaptive pulsed. Experiments are then performed using Synergic Pulsed GMAW, WiseFusionTM and Synergic GMAW processes to weld a T-joint in a horizontal position (PB). The air gap between the parts ranges from 0 to 2.5 mm. The base materials are structural steel grade S355MC and filler material G3Si1. The experiment investigates heat input, mechanical properties and microstructure of the welded joint. Analysis of the literature reveals that different approaches have been suggested using advanced digital power sources with accurate waveform, current, voltage, and feedback control. In addition, studies have clearly indicated the efficiency of lower energy welding processes. Interest in the high power range is growing and a number of different approaches have been suggested. The welding experiments in this study reveal a significant reduction of heat input and a weld microstructure with the presence of acicular ferrite (AF) beneficial for resistance to crack propagation. The WiseFusion bead had higher dilution, due to the weld bead shape, and low defects. Adaptive pulse GMAW processes can be a favoured choice when welding structures with many welded joints. The total heat reduction mitigates residual stresses and the bead shape allows a higher amperage limit. The stability of the arc during the process is virtually spatter free and allows an increase in welding speed.

Mapping financial stability

The ongoing global financial crisis has demonstrated the importance of a systemwide, or macroprudential, approach to safeguarding financial stability. An essential part of macroprudential oversight concerns the tasks of early identification and assessment of risks and vulnerabilities that eventually may lead to a systemic financial crisis. Thriving tools are crucial as they allow early policy actions to decrease or prevent further build-up of risks or to otherwise enhance the shock absorption capacity of the financial system. In the literature, three types of systemic risk can be identified: i ) build-up of widespread imbalances, ii ) exogenous aggregate shocks, and iii ) contagion. Accordingly, the systemic risks are matched by three categories of analytical methods for decision support: i ) early-warning, ii ) macro stress-testing, and iii ) contagion models. Stimulated by the prolonged global financial crisis, today's toolbox of analytical methods includes a wide range of innovative solutions to the two tasks of risk identification and risk assessment. Yet, the literature lacks a focus on the task of risk communication. This thesis discusses macroprudential oversight from the viewpoint of all three tasks: Within analytical tools for risk identification and risk assessment, the focus concerns a tight integration of means for risk communication. Data and dimension reduction methods, and their combinations, hold promise for representing multivariate data structures in easily understandable formats. The overall task of this thesis is to represent high-dimensional data concerning financial entities on lowdimensional displays. The low-dimensional representations have two subtasks: i ) to function as a display for individual data concerning entities and their time series, and ii ) to use the display as a basis to which additional information can be linked. The final nuance of the task is, however, set by the needs of the domain, data and methods. The following ve questions comprise subsequent steps addressed in the process of this thesis: 1. What are the needs for macroprudential oversight? 2. What form do macroprudential data take? 3. Which data and dimension reduction methods hold most promise for the task? 4. How should the methods be extended and enhanced for the task? 5. How should the methods and their extensions be applied to the task? Based upon the Self-Organizing Map (SOM), this thesis not only creates the Self-Organizing Financial Stability Map (SOFSM), but also lays out a general framework for mapping the state of financial stability. This thesis also introduces three extensions to the standard SOM for enhancing the visualization and extraction of information: i ) fuzzifications, ii ) transition probabilities, and iii ) network analysis. Thus, the SOFSM functions as a display for risk identification, on top of which risk assessments can be illustrated. In addition, this thesis puts forward the Self-Organizing Time Map (SOTM) to provide means for visual dynamic clustering, which in the context of macroprudential oversight concerns the identification of cross-sectional changes in risks and vulnerabilities over time. Rather than automated analysis, the aim of visual means for identifying and assessing risks is to support disciplined and structured judgmental analysis based upon policymakers' experience and domain intelligence, as well as external risk communication.

Model-Based Tracking Initialization in Ship Building Environment

An augmented reality (AR) device must know observer’s location and orientation, i.e. observer’s pose, to be able to correctly register the virtual content to observer’s view. One possible way to determine and continuously follow-up the pose is model-based visual tracking. It supposes that a 3D model of the surroundings is known and that there is a video camera that is fixed to the device. The pose is tracked by comparing the video camera image to the model. Each new pose estimate is usually based on the previous estimate. However, the first estimate must be found out without a prior estimate, i.e. the tracking must be initialized, which in practice means that some model features must be identified from the image and matched to model features. This is known in literature as model-to-image registration problem or simultaneous pose and correspondence problem. This report reviews visual tracking initialization methods that are suitable for visual tracking in ship building environment when the ship CAD model is available. The environment is complex, which makes the initialization non-trivial. The report has been done as part of MARIN project.

The Straits of Seniavine : Behring Straits by the U.S. Ship Vincennes

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Stability of Natural Colorants of Plant Origin

In recent years, there have been studies that show a correlation between the hyperactivity of children and use of artificial food additives, including colorants. This has, in part, led to preference of natural products over products with artificial additives. Consumers have also become more aware of health issues. Natural food colorants have many bioactive functions, mainly vitamin A activity of carotenoids and antioxidativity, and therefore they could be more easily accepted by the consumers. However, natural colorant compounds are usually unstable, which restricts their usage. Microencapsulation could be one way to enhance the stability of natural colorant compounds and thus enable better usage for them as food colorants. Microencapsulation is a term used for processes in which the active material is totally enveloped in a coating or capsule, and thus it is separated and protected from the surrounding environment. In addition to protection by the capsule, microencapsulation can also be used to modify solubility and other properties of the encapsulated material, for example, to incorporate fat-soluble compounds into aqueous matrices. The aim of this thesis work was to study the stability of two natural pigments, lutein (carotenoid) and betanin (betalain), and to determine possible ways to enhance their stability with different microencapsulation techniques. Another aim was the extraction of pigments without the use of organic solvents and the development of previously used extraction methods. Stability of pigments in microencapsulated pigment preparations and model foods containing these were studied by measuring the pigment content after storage in different conditions. Preliminary studies on the bioavailability of microencapsulated pigments and sensory evaluation for consumer acceptance of model foods containing microencapsulated pigments were also carried out. Enzyme-assisted oil extraction was used to extract lutein from marigold (Tagetes erecta) flower without organic solvents, and the yield was comparable to solvent extraction of lutein from the same flowers. The effects of temperature, extraction time, and beet:water ratio on extraction efficiency of betanin from red beet (Beta vulgaris) were studied and the optimal conditions for maximum yield and maximum betanin concentration were determined. In both cases, extraction at 40 °C was better than extraction at 80 °C and the extraction for five minutes was as efficient as 15 or 30 minutes. For maximum betanin yield, the beet:water ratio of 1:2 was better, with possibly repeated extraction, but for maximum betanin concentration, a ratio of 1:1 was better. Lutein was incorporated into oil-in-water (o/w) emulsions with a polar oil fraction from oat (Avena sativa) as an emulsifier and mixtures of guar gum and xanthan gum or locust bean gum and xanthan gum as stabilizers to retard creaming. The stability of lutein in these emulsions was quite good, with 77 to 91 percent of lutein being left after storage in the dark at 20 to 22°C for 10 weeks whereas in spray dried emulsions the retention of lutein was 67 to 75 percent. The retention of lutein in oil was also good at 85 percent. Betanin was incorporated into the inner w1 water phase of a water1-in-oil-inwater2 (w1/o/w2) double emulsion with primary w1/o emulsion droplet size of 0.34 μm and secondary w1/o/w2 emulsion droplet size of 5.5 μm and encapsulation efficiency of betanin of 89 percent. In vitro intestinal lipid digestion was performed on the double emulsion, and during the first two hours, coalescence of the inner water phase droplets was observed, and the sizes of the double emulsion droplets increased quickly because of aggregation. This period also corresponded to gradual release of betanin, with a final release of 35 percent. The double emulsion structure was retained throughout the three-hour experiment. Betanin was also spray dried and incorporated into model juices with different pH and dry matter content. Model juices were stored in the dark at -20, 4, 20–24 or 60 °C (accelerated test) for several months. Betanin degraded quite rapidly in all of the samples and higher temperature and a lower pH accelerated degradation. Stability of betanin was much better in the spray dried powder, with practically no degradation during six months of storage in the dark at 20 to 24 °C and good stability also for six months in the dark at 60 °C with 60 percent retention. Consumer acceptance of model juices colored with spray dried betanin was compared with similar model juices colored with anthocyanins or beet extract. Consumers preferred beet extract and anthocyanin colored model juices over juices colored with spray dried betanin. However, spray dried betanin did not impart any off-odors or off-flavors into the model juices contrary to the beet extract. In conclusion, this thesis describes novel solvent-free extraction and encapsulation processes for lutein and betanin from plant sources. Lutein showed good stability in oil and in o/w emulsions, but slightly inferior in spray dried emulsions. In vitro intestinal lipid digestion showed a good stability of w1/o/w2 double emulsion and quite high retention of betanin during digestion. Consumer acceptance of model juices colored with spray dried betanin was not as good as model juices colored with anthocyanins, but addition of betanin to real berry juice could produce better results with mixture of added betanin and natural berry anthocyanins could produce a more acceptable color. Overall, further studies are needed to obtain natural colorants with good stability for the use in food products.

St. Lawrence Bay showing Lutke's Harbor by the U.S. Ship Vincennes : lieutenant John Rodgers September 1855

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Part of the Arctic Ocean reconnoitered in the U.S. Ship Vincennes

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Stability Analysis in Multicriteria Discrete Portfolio Optimization.

Almost every problem of design, planning and management in the technical and organizational systems has several conflicting goals or interests. Nowadays, multicriteria decision models represent a rapidly developing area of operation research. While solving practical optimization problems, it is necessary to take into account various kinds of uncertainty due to lack of data, inadequacy of mathematical models to real-time processes, calculation errors, etc. In practice, this uncertainty usually leads to undesirable outcomes where the solutions are very sensitive to any changes in the input parameters. An example is the investment managing. Stability analysis of multicriteria discrete optimization problems investigates how the found solutions behave in response to changes in the initial data (input parameters). This thesis is devoted to the stability analysis in the problem of selecting investment project portfolios, which are optimized by considering different types of risk and efficiency of the investment projects. The stability analysis is carried out in two approaches: qualitative and quantitative. The qualitative approach describes the behavior of solutions in conditions with small perturbations in the initial data. The stability of solutions is defined in terms of existence a neighborhood in the initial data space. Any perturbed problem from this neighborhood has stability with respect to the set of efficient solutions of the initial problem. The other approach in the stability analysis studies quantitative measures such as stability radius. This approach gives information about the limits of perturbations in the input parameters, which do not lead to changes in the set of efficient solutions. In present thesis several results were obtained including attainable bounds for the stability radii of Pareto optimal and lexicographically optimal portfolios of the investment problem with Savage's, Wald's criteria and criteria of extreme optimism. In addition, special classes of the problem when the stability radii are expressed by the formulae were indicated. Investigations were completed using different combinations of Chebyshev's, Manhattan and Hölder's metrics, which allowed monitoring input parameters perturbations differently.

Stability and properties of cellulose-sodium hydroxide solution systems

Since cellulose is a linear macromolecule it can be used as a material for regenerated cellulose fiber products e.g. in textile fibers or film manufacturing. Cellulose is not thermoformable, thus the manufacturing of these regenerated fibers is mainly possible through dissolution processes preceding the regeneration process. However, the dissolution of cellulose in common solvents is hindered due to inter- and intra-molecular hydrogen bonds in the cellulose chains, and relatively high crystallinity. Interestingly at subzero temperatures relatively dilute sodium hydroxide solutions can be used to dissolve cellulose to a certain extent. The objective of this work was to investigate the possible factors that govern the solubility of cellulose in aqueous NaOH and the solution stability. Cellulose-NaOH solutions have the tendency to form a gel over time and at elevated temperature, which creates challenges for further processing. The main target of this work was to achieve high solubility of cellulose in aqueous NaOH without excessively compromising the solution stability. In the literature survey an overview of the cellulose dissolution is given and possible factors contributing to the solubility and solution properties of cellulose in aqueous NaOH are reviewed. Furthermore, the concept of solution rheology is discussed. In the experimental part the focus was on the characterization of the used materials and properties of the prepared solutions mainly concentrating on cellulose solubility and solution stability.

Effect of ambient conditions on dimensional stability and stiffness of commercial paperboard and paperboard trays

The objective of this study was to develop laboratory test methods for characterizing the effects of changed moisture content on paperboard trays produced by press-forming process. Influence of moisture on the properties of unconverted paperboard such as bending stiffness, bursting strength, and curling was studied. Paperboard and tray samples were tested after storing in different relative humidity conditions (35, 50, 65, 80 and 95% RH). The effect of PE and PET extrusion coatings on these properties was also studied. It was found that increase in moisture content of paperboard decreases bending and bursting strength, dimensional stability and stiffness of paperboard trays. Such physical and mechanical properties as bending stiffness and curling of paperboard seem to define the stiffness of ready-made trays and their dimensional stability. Paperboards and trays with extruded PE and PET one sided coatings demonstrated higher strength properties but at the same time had lower dimensional stability comparing to uncoated paperboards. Samples with smaller polymer coat weight had better dimensional stability than respective samples with higher coat weight. It was also found that preconditioning of paperboard in lower humidity environment before press-forming could improve dimensional stability and stiffness of ready-made tray.

Stability and predictive ability of beta

The purpose of this paper is to examine the stability and predictive abilities of the beta coefficients of individual equities in the Finnish stock market. As beta is widely used in several areas of finance, including risk management, asset pricing and performance evaluation among others, it is important to understand its characteristics and find out whether its estimates can be trusted and utilized.

The way to organizational longevity - Balancing stability and change in Shinise firms

THE WAY TO ORGANIZATIONAL LONGEVITY – Balancing stability and change in Shinise firms The overall purpose of this dissertation is to investigate the secret of longevity in Shinise firms. On the basic assumption that organizational longevity is about balancing stability and change, the theoretical perspectives incorporate routine practice, organizational culture, and organizational identity. These theories explain stability and change in an organization separately and in combination. Qualitative inductive theory building was used in the study. Overall, the empirical data comprised 75 in-depth and semi-structured interviews, 137 archival materials, and observations made over 17 weeks. According to the empirical findings, longevity in Shinise firms is attributable to the internal mechanisms (Shinise tenacity, stability in motion, and emergent change) to secure a balance between stability and change, the continuing stability of the socio-cultural environment in the local community, and active interaction between organizational and local cultures. The contribution of the study to the literature on organizational longevity and the alternative theoretical approaches is first, in theorizing the mechanisms of Shinise tenacity and cross-level cultural dynamism, and second, in pointing out the critical role of: the way firms set their ultimate goal, the dynamism in culture, and the effect of history of the firm to the current business in securing longevity. KEY WORDS Change; Culture; Organizational identity; Organizational longevity; Routines; Shinise firms; Stability; Qualitative research

“Who is steering the ship and which constellation guides the way? Exploring transparency in the European Central Bank during the time of crisis”

This paper explores transparency in the decision-making of the European Central Bank (ECB). According to ECB´s definition, transparency means that the central bank provides the general public with all relevant information on its strategy, assessments and policy decisions as well as its procedures in an open, clear and timely manner. In this paper, however, the interpretation of transparency is somewhat broader: Information is freely available and directly accessible to those who will be affected by the decisions. Moreover, the individuals shall be able to master this material. ECB´s negative attitude towards publication of documents has demonstrated central bank´s reluctance to strive towards more extensive transparency. By virtue of the definition adopted by the ECB the bank itself is responsible for determining what is considered as relevant information. On the grounds of EU treaties, this paper assesses ECB`s accountability concentrating especially on transparency by employing principal-agent theory and constitutional approach. Traditionally, the definite mandate and the tenet of central bank independence have been used to justify the limited accountability. The de facto competence of the ECB has, however, considerably expanded as the central bank has decisively resorted to non-standard measures in order to combat the economic turbulences facing Europe. It is alleged that non-standard monetary policy constitutes a grey zone occasionally resembling economic policy or fiscal policy. Notwithstanding, the European Court of Justice has repeatedly approved these measures. This dynamic interpretation of the treaties seems to allow temporarily exceptions from the central bank´s primary objective during extraordinary times. Regardless, the paper suggests that the accountability nexus defined in the treaties is not sufficient in order to guarantee the accountability of the ECB after the adoption of the new, more active role. Enhanced transparency would help the ECB to maintain its credibility. Investing in the quality of monetary dialogue between the Parliament and the ECB appears to constitute the most adequate and practicable method to accomplish this intention. As a result of upgraded transparency the legitimacy of the central bank would not solely rest on its policy outputs.