Generation and Characterization of Knockout Mice and Analysis of Patient Material Demonstrates a Role for Tissue Inhibitor of Metalloproteinases 4 (Timp4) in the Cardiovascular System and Tumor Metastasis

This thesis focuses on tissue inhibitor of metalloproteinases 4 (TIMP4) which is the newest member of a small gene and protein family of four closely related endogenous inhibitors of extracellular matrix (ECM) degrading enzymes. Existing data on TIMP4 suggested that it exhibits a more restricted expression pattern than the other TIMPs with high expression levels in heart, brain, ovary and skeletal muscle. These observations and the fact that the ECM is of special importance to provide the cardiovascular system with structural strength combined with elasticity and distensibility, prompted the present molecular biologic investigation on TIMP4. In the first part of the study the murine Timp4 gene was cloned and characterized in detail. The structure of murine Timp4 genomic locus resembles that in other species and of the other Timps. The highest Timp4 expression was detected in heart, ovary and brain. As the expression pattern of Timp4 gives only limited information about its role in physiology and pathology, Timp4 knockout mice were generated next. The analysis of Timp4 knockout mice revealed that Timp4 deficiency has no obvious effect on the development, growth or fertility of mice. Therefore, Timp4 deficient mice were challenged using available cardiovascular models, i.e. experimental cardiac pressure overload and myocardial infarction. In the former model, Timp4 deficiency was found to be compensated by Timp2 overexpression, whereas in the myocardial infarct model, Timp4 deficiency resulted in increased mortality due to increased susceptibility for cardiac rupture. In the wound healing model, Timp4 deficiency was shown to result in transient retardation of re-epithelialization of cutaneous wounds. Melanoma tumor growth was similar in Timp4 deficient and control mice. Despite of this, lung metastasis of melanoma cells was significantly increased in Timp4 null mice. In an attempt to translate the current findings to patient material, TIMP4 expression was studied in human specimens representing different inflammatory cardiovascular pathologies, i.e. giant cell arteritis, atherosclerotic coronary arteries and heart allografts exhibiting signs of chronic rejection. The results showed that cardiovascular expression of TIMP4 is elevated particularly in areas exhibiting inflammation. The results of the present studies suggest that TIMP4 has a special role in the regulation of tissue repair processes in the heart, and also in healing wounds and metastases. Furthermore, evidence is provided suggesting the usefulness of TIMP4 as a novel systemic marker for vascular inflammation.

En generation intellektuella i uppror

Kirjallisuusarvostelu

Building object-oriented software with the D-Bus messaging system

Object-oriented programming is a widely adopted paradigm for desktop software development. This paradigm partitions software into separate entities, objects, which consist of data and related procedures used to modify and inspect it. The paradigm has evolved during the last few decades to emphasize decoupling between object implementations, via means such as explicit interface inheritance and event-based implicit invocation. Inter-process communication (IPC) technologies allow applications to interact with each other. This enables making software distributed across multiple processes, resulting in a modular architecture with benefits in resource sharing, robustness, code reuse and security. The support for object-oriented programming concepts varies between IPC systems. This thesis is focused on the D-Bus system, which has recently gained a lot of users, but is still scantily researched. D-Bus has support for asynchronous remote procedure calls with return values and a content-based publish/subscribe event delivery mechanism. In this thesis, several patterns for method invocation in D-Bus and similar systems are compared. The patterns that simulate synchronous local calls are shown to be dangerous. Later, we present a state-caching proxy construct, which avoids the complexity of properly asynchronous calls for object inspection. The proxy and certain supplementary constructs are presented conceptually as generic object-oriented design patterns. The e ect of these patterns on non-functional qualities of software, such as complexity, performance and power consumption, is reasoned about based on the properties of the D-Bus system. The use of the patterns reduces complexity, but maintains the other qualities at a good level. Finally, we present currently existing means of specifying D-Bus object interfaces for the purposes of code and documentation generation. The interface description language used by the Telepathy modular IM/VoIP framework is found to be an useful extension of the basic D-Bus introspection format.

Legal challenges for next generation science

Presentation at the Nordic Perspectives on Open Access and Open Science seminar, Helsinki, October 15, 2013

Building Next Generation Consortium Services – part 3: The National Metadata Repository, Discovery Service Finna, and the New Library System

Kristiina Hormia-Poutasen esitys CBUC-konferenssissa Barcelonassa 12.4.2013.

Building Next Generation Consortium Services – part 1: Background for Change

Kristiina Hormia-Poutasen esitys CBUC-konferenssissa Barcelonassa 12.4.2013.

Building Next Generation Consortium Services – part 2: Next Generation IT-services – Why, What, When?

Kristiina Hormia-Poutasen esitys CBUC-konferenssissa Barcelonassa 12.4.2013.

Building Next Generation Consortium Services – Introduction to the seminar

Kristiina Hormia-Poutasen esitys CBUC-konferenssissa 12.4.2013 Barcelonassa.

Creating generation Y sources of motivation for enhanced performance

New challenges have been created in the modern work environment as the diversity of the workforce is greater than ever in terms of generations. There will become a large demand of generation Y employees as the baby boomer generation employees retire at an accelerated rate. The purpose of this study is to investigate Y generation specific characteristics and to identify motivational systems to enhance performance. The research questions are: 1. What are Y generation characteristics? 2. What motivational systems organizations can form to motivate Y generation employees and in turn, create better performance? The Y generation specific characteristics identified from the literature include; achievement oriented; confident; educated; multitasking; having a need for feedback; needing management support; sociable and tech savvy. The proposed motivational systems can be found in four areas of the organization; HRM, training and development, communication and decision making policies. Three focus groups were held to investigate what would motivate generation Y employees to achieve better performance. Two of these focus groups were Finnish natives and the third consisted of international students. The HRM systems included flexibility and a culture of fun. It was concluded that flexibility within the workplace and role was a great source of motivation. Culture of fun was not responded to as favorably although most focus group participants rated enjoyableness as one of their top motivating factors. Training and development systems include training programs and mentoring as sources of potential motivation. Training programs were viewed as a mode to gain a better position and were not necessarily seen as motivational systems. Mentoring programs were not concluded to have a significant effect on motivation. Communication systems included keeping up with technology, clarity and goals as well as feedback. Keeping up with technology was seen as an ineffective tool to motivate. Clarity and goal setting was seen as very important to be able to perform but not necessarily motivating. Feedback had a highly motivating effect on these focus groups. Decision making policies included collaboration and teamwork as well as ownership. Teams were familiar and meet the social needs of Y generation employees and are motivating. Ownership was equated with trust and responsibility and was highly valued as well as motivating to these focus group participants.

Reaching influential early adopters effectively in Finland : Rock Science – new generation board game

Innovations diffuse at different speed among the members of a social system through various communication channels. The group of early adopters can be seen as the most influential reference group for majority of people to base their innovation adoption decisions on. Thus, the early adopters can often accelerate the diffusion of innovations. The purpose of this research is to discover means of diffusion for an innovative product in Finnish market through the influential early adopters in respect to the characteristics of the case product. The purpose of the research can be achieved through the following sub objectives:  Who are the potential early adopters for the case product and why?  How the potential early adopters of the case product should be communicated with?  What would be the expectations, preferences, and experiences of the early adopters of the case product? The case product examined in this research is a new board game called Rock Science which is considered to be incremental innovation bringing board gaming and hard rock music together in a new way. The research was conducted in two different parts using both qualitative and quantitative research methods. This mixed method research began with expert interviews of six music industry experts. The information gathered from the interviews enabled researcher to compose the questionnaire for the quantitative part of the study. Internet survey that was sent out resulted with a sample of 97 responses from the targeted population. The key findings of the study suggest that (1) the potential early adopters for the case product are more likely to be young adults from the capital city area with great interest in rock music, (2) the early adopters can be reached effectively through credible online sources of information, and (3) the respondents overall product feedback is highly positive, except in the case of quality-price ratio of the product. This research indicates that more effective diffusion of Rock Science board game in Finland can be reached through (1) strategic alliances with music industry and media partnerships, (2) pricing adjustments, (3) use of supporting game formats, and (4) innovative use of various social media channels.

Software and Code Finder: making research outputs visible

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

VVER-440 Thermal Hydraulics as a Computer Code Validation Challenge

This thesis concentrates on the validation of a generic thermal hydraulic computer code TRACE under the challenges of the VVER-440 reactor type. The code capability to model the VVER-440 geometry and thermal hydraulic phenomena specific to this reactor design has been examined and demonstrated acceptable. The main challenge in VVER-440 thermal hydraulics appeared in the modelling of the horizontal steam generator. The major challenge here is not in the code physics or numerics but in the formulation of a representative nodalization structure. Another VVER-440 specialty, the hot leg loop seals, challenges the system codes functionally in general, but proved readily representable. Computer code models have to be validated against experiments to achieve confidence in code models. When new computer code is to be used for nuclear power plant safety analysis, it must first be validated against a large variety of different experiments. The validation process has to cover both the code itself and the code input. Uncertainties of different nature are identified in the different phases of the validation procedure and can even be quantified. This thesis presents a novel approach to the input model validation and uncertainty evaluation in the different stages of the computer code validation procedure. This thesis also demonstrates that in the safety analysis, there are inevitably significant uncertainties that are not statistically quantifiable; they need to be and can be addressed by other, less simplistic means, ultimately relying on the competence of the analysts and the capability of the community to support the experimental verification of analytical assumptions. This method completes essentially the commonly used uncertainty assessment methods, which are usually conducted using only statistical methods.

Development of an HTR-10 model in the Serpent reactor physics code

The use of exact coordinates of pebbles and fuel particles of pebble bed reactor modelling becoming possible in Monte Carlo reactor physics calculations is an important development step. This allows exact modelling of pebble bed reactors with realistic pebble beds without the placing of pebbles in regular lattices. In this study the multiplication coefficient of the HTR-10 pebble bed reactor is calculated with the Serpent reactor physics code and, using this multiplication coefficient, the amount of pebbles required for the critical load of the reactor. The multiplication coefficient is calculated using pebble beds produced with the discrete element method and three different material libraries in order to compare the results. The received results are lower than those from measured at the experimental reactor and somewhat lower than those gained with other codes in earlier studies.