Choosing the target loci : heat shock factors HSF1 and HSF2 as regulators of cell stress and development

Heat shock factors (HSFs) are an evolutionarily well conserved family of transcription factors that coordinate stress-induced gene expression and direct versatile physiological processes in eukaryote organisms. The essentiality of HSFs for cellular homeostasis has been well demonstrated, mainly through HSF1-induced transcription of heat shock protein (HSP) genes. HSFs are important regulators of many fundamental processes such as gametogenesis, metabolic control and aging, and are involved in pathological conditions including cancer progression and neurodegenerative diseases. In each of the HSF-mediated processes, however, the detailed mechanisms of HSF family members and their complete set of target genes have remained unknown. Recently, rapid advances in chromatin studies have enabled genome-wide characterization of protein binding sites in a high resolution and in an unbiased manner. In this PhD thesis, these novel methods that base on chromatin immunoprecipitation (ChIP) are utilized and the genome-wide target loci for HSF1 and HSF2 are identified in cellular stress responses and in developmental processes. The thesis and its original publications characterize the individual and shared target genes of HSF1 and HSF2, describe HSF1 as a potent transactivator, and discover HSF2 as an epigenetic regulator that coordinates gene expression throughout the cell cycle progression. In male gametogenesis, novel physiological functions for HSF1 and HSF2 are revealed and HSFs are demonstrated to control the expression of X- and Y-chromosomal multicopy genes in a silenced chromatin environment. In stressed human cells, HSF1 and HSF2 are shown to coordinate the expression of a wide variety of genes including genes for chaperone machinery, ubiquitin, regulators of cell cycle progression and signaling. These results highlight the importance of cell type and cell cycle phase in transcriptional responses, reveal the myriad of processes that are adjusted in a stressed cell and describe novel mechanisms that maintain transcriptional memory in mitotic cell division.

Osaamisen johtaminen - käytäntöjä ja kehittämistarpeita henkilöstön näkökulmasta

Tämän pro gradu -tutkimuksen tavoitteena oli tutkia osaamisen johtamisen käytäntöjä ja kehittämistarpeita kohdeorganisaatiossa henkilöstön näkökulmasta. Tutkimuksen tarkoituksena oli selvittää, miten tehtyjä henkilöstötutkimuksia on hyödynnetty kohdeorganisaatiossa ja näkyykö tämä hyödyntäminen käytännön johtamisessa henkilöstön mielestä. Tutkimus suoritettiin laadullisena tapaustutkimuksena ja empiirinen aineisto kerättiin kuudella teemahaastattelulla, jotka analysoitiin sisällönanalyysimenetelmällä. Tutkimuksessa kartoitettiin, millaisia osaamisen johtamisen käytäntöjä kohdeorganisaatiossa on. Tutkimuksen tuloksien perusteella osaamisen johtamisen peruselementit ovat olemassa: säännölliset palaverit koettiin tärkeiksi, mutta koulutuksien ja kehityskeskusteluiden järjestämisessä sekä jälkiseurannassa henkilöstö näki parannettavaa. Myös hiljaisen tiedon siirtäminen ja hyödyntäminen koettiin merkittäväksi tekijäksi organisaation onnistuneen toiminnan ja jatkuvuuden kannalta. Tutkimuksessa todettiin osaamisen johtamisen kehittämisen ja osaamisen kehittämisen menetelmien linkittyvän vahvasti toisiinsa ja tutkimuksen tuloksena esitettiin konkreettisia toimenpide-ehdotuksia osaamisen johtamisen kehittämisestä kohdeorganisaation johdolle. Tutkimuksen mukaan osaamisen johtaminen ja henkilöstöjohtaminen sulautuvat toisiinsa, eikä niitä voida tarkastella erikseen. Johdon ja henkilöstön välisellä vuorovaikutuksella on suuri merkitys onnistuneelle osaamisen johtamiselle. Keskeistä on kytkeä osaamisen johtaminen organisaation käytäntöihin ja varata sen implementointiin riittävästi resursseja.

Application and development of numerical methods for the modelling of innovative gas cooled fission reactors

Innovative gas cooled reactors, such as the pebble bed reactor (PBR) and the gas cooled fast reactor (GFR) offer higher efficiency and new application areas for nuclear energy. Numerical methods were applied and developed to analyse the specific features of these reactor types with fully three dimensional calculation models. In the first part of this thesis, discrete element method (DEM) was used for a physically realistic modelling of the packing of fuel pebbles in PBR geometries and methods were developed for utilising the DEM results in subsequent reactor physics and thermal-hydraulics calculations. In the second part, the flow and heat transfer for a single gas cooled fuel rod of a GFR were investigated with computational fluid dynamics (CFD) methods. An in-house DEM implementation was validated and used for packing simulations, in which the effect of several parameters on the resulting average packing density was investigated. The restitution coefficient was found out to have the most significant effect. The results can be utilised in further work to obtain a pebble bed with a specific packing density. The packing structures of selected pebble beds were also analysed in detail and local variations in the packing density were observed, which should be taken into account especially in the reactor core thermal-hydraulic analyses. Two open source DEM codes were used to produce stochastic pebble bed configurations to add realism and improve the accuracy of criticality calculations performed with the Monte Carlo reactor physics code Serpent. Russian ASTRA criticality experiments were calculated. Pebble beds corresponding to the experimental specifications within measurement uncertainties were produced in DEM simulations and successfully exported into the subsequent reactor physics analysis. With the developed approach, two typical issues in Monte Carlo reactor physics calculations of pebble bed geometries were avoided. A novel method was developed and implemented as a MATLAB code to calculate porosities in the cells of a CFD calculation mesh constructed over a pebble bed obtained from DEM simulations. The code was further developed to distribute power and temperature data accurately between discrete based reactor physics and continuum based thermal-hydraulics models to enable coupled reactor core calculations. The developed method was also found useful for analysing sphere packings in general. CFD calculations were performed to investigate the pressure losses and heat transfer in three dimensional air cooled smooth and rib roughened rod geometries, housed inside a hexagonal flow channel representing a sub-channel of a single fuel rod of a GFR. The CFD geometry represented the test section of the L-STAR experimental facility at Karlsruhe Institute of Technology and the calculation results were compared to the corresponding experimental results. Knowledge was gained of the adequacy of various turbulence models and of the modelling requirements and issues related to the specific application. The obtained pressure loss results were in a relatively good agreement with the experimental data. Heat transfer in the smooth rod geometry was somewhat under predicted, which can partly be explained by unaccounted heat losses and uncertainties. In the rib roughened geometry heat transfer was severely under predicted by the used realisable k − epsilon turbulence model. An additional calculation with a v2 − f turbulence model showed significant improvement in the heat transfer results, which is most likely due to the better performance of the model in separated flow problems. Further investigations are suggested before using CFD to make conclusions of the heat transfer performance of rib roughened GFR fuel rod geometries. It is suggested that the viewpoints of numerical modelling are included in the planning of experiments to ease the challenging model construction and simulations and to avoid introducing additional sources of uncertainties. To facilitate the use of advanced calculation approaches, multi-physical aspects in experiments should also be considered and documented in a reasonable detail.

Comparison of Different Concentrated Solar Power Collector Designs and Development of a Linear Fresnel Solar Collector Model

Concentrated solar power (CSP) is a renewable energy technology, which could contribute to overcoming global problems related to pollution emissions and increasing energy demand. CSP utilizes solar irradiation, which is a variable source of energy. In order to utilize CSP technology in energy production and reliably operate a solar field including thermal energy storage system, dynamic simulation tools are needed in order to study the dynamics of the solar field, to optimize production and develop control systems. The object of this Master’s Thesis is to compare different concentrated solar power technologies and configure a dynamic solar field model of one selected CSP field design in the dynamic simulation program Apros, owned by VTT and Fortum. The configured model is based on German Novatec Solar’s linear Fresnel reflector design. Solar collector components including dimensions and performance calculation were developed, as well as a simple solar field control system. The preliminary simulation results of two simulation cases under clear sky conditions were good; the desired and stable superheated steam conditions were maintained in both cases, while, as expected, the amount of steam produced was reduced in the case having lower irradiation conditions. As a result of the model development process, it can be concluded, that the configured model is working successfully and that Apros is a very capable and flexible tool for configuring new solar field models and control systems and simulating solar field dynamic behaviour.

Supplier segmentation and development in project business

The purpose of this study was to expand the applicability of supplier segmentation and development approaches to the project-driven construction industry. These practices are less exploited and not well documented in this operational environment compared to the process-centric manufacturing industry. At first, portfolio models to supply base segmentation and various supplier development efforts were investigated in literature review. A step-wise framework was structured for the empirical research. The empirical study employed multiple research methods in three case studies in a large Finnish construction company. The first study categorized the construction item classes into the purchasing portfolio and positioned suppliers to the power matrix by investigating buyer-supplier relations. Using statistical tests, the study also identified factors that affect suppliers’ performance. The final case study identified improvement areas of the interface between a main contractor and one if its largest suppliers. The final results indicate that only by assessing the supply base in a holistic manner and the power circumstances in it, buyers comprehend how to best establish appropriate supplier development strategies in the project environment.

Intellectual capital, knowledge management practices and firm performance

Researchers have widely recognised and accepted that firm performance is increasingly related to knowledge-based issues. Two separately developed literature streams, intellectual capital (IC) and knowledge management (KM), have been established as the key discussions related to knowledge-based competitive advantage of the firm. Intellectual capital has provided evidence on the strategic key intangible resources of the firm, which could be deployed to create competitive advantage. Knowledge management, in turn, has focused on the managerial processes and practices which can be used to leverage IC to create competitive advantage. Despite extensive literature on both issues, some notable research gaps remain to be closed. In effect, one major gap within the knowledge management research is the lack of understanding related to its influence on firm performance, while IC researchers have articulated a need to utilise more finegrained conceptual models to better understand the key strategic value-creating resources of the firm. In this dissertation, IC is regarded as the entire intellectual capacity, knowledge and competences of the firm that can be leveraged to achieve sustained competitive advantage. KM practices are defined as organisational and managerial activities that enable the firm to leverage its IC to create value. The objective of this dissertation is to answer the research question: “What is the relationship between intellectual capital, knowledge management practices and firm performance?” Five publications have addressed the research question using different approaches. The first two publications were systematic literature reviews of the extant empirical IC and KM research, which established the current state of understanding regarding the relationship between IC, KM practices and firm performance. Publications III and IV were empirical research articles that assessed the developed conceptual model related to IC, KM practices and firm performance. Finally, Publication V was among the first research papers to merge IC and KM disciplines in order to find out which configurations could yield organisational benefits in terms of innovation and market performance outcomes.