Modulation of TGF-β signaling by Hypoxia

A tumor is a fast-growing malignant tissue. This creates areas inside the tumor that are distant from local blood vessels to be able to get enough oxygen. This hypoxic condition activates a transcription factor called hypoxia inducible factor (HIF). HIF responses help a cell to adapt to decreased oxygen by activating glycolytic and angiogenesis pathways and by regulating apoptotic responses. Hypoxia drives the upregulation of a growth factor called transforming growth factor beta (TGF-beta). Similar to a hypoxia response, TGF is an important regulator of cell fate. TGF-β and HIF pathways regulate partially overlapping target genes. This regulation can also be cooperative. The TGF-beta signal is initiated by activation of plasma membrane receptors that then activate effector proteins called small mothers against decapentaplegic (Smad) homologs. In healthy tissue, TGF-β keeps cell proliferation and growth under control. During cancer progression, TGF-beta has shown a dual role, whereby it inhibits initial tumor formation but, conversely, in an existent tumor, TGF-beta drives malignant progression. Along with HIF and TGF-beta also protein dephosphorylation is an important regulatory mechanism of cell fate. Protein dephosphorylation is catalyzed by protein phosphatases such as Protein phosphatase 2A (PP2A). PP2A is a ubiquitous phosphatase that can exist in various active forms. PP2A can specifically regulate TGF-beta signaling either by enhancing or inhibiting the receptor activity. This work demonstrates that during hypoxia, PP2A is able to fine-tune TGF-beta signal by specifically targeting Smad3 effector in a Smad7-dependent manner. Inactivation of Smad3 in hypoxia leads to malignant conversion of TGF-beta signaling.

Developing asset management in district heating and cooling business in a large energy company

The purpose of this Master´s Thesis is to develop asset management and its practices in case company. District heating and cooling systems operated by case company around Finland, Sweden, Poland and the Baltics form an enormous-sized asset base where some parts are starting to reach their end of life-cycles. Large-sized asset renewal actions are under discussion and maintenance spending is increasing. Financially justified decisions in changing business environment are needed. Asset management is one of the most important concepts for production organization which operates with capital-intensive production assets. Organizations profitability is highly dependent on assets´ performance. Such assets, like district heating and cooling systems, should be utilized as efficiently as possible within their life-cycles but also maintained and renewed optimally. In this qualitative thesis, empirical interview study was conducted to describe the current situation on how the assets are managed in the case company and to examine the readiness to implement a new, risk-based solution. Asset management revealed to be a very well-known concept. From proposed risk-based asset management point of view, several key observations were made. It was seen as a suitable solution, but further development will be needed. Based on the need and findings, several key processes and frameworks were created and also tested with a case study. Assets` condition monitoring should be improved, which would have a positive impact on event probability assessment. Risk acceptance is also a thing to be discussed further. When the evaluation becomes fluent in single investment cases, portfolio-level expansion should be considered and started. As a result, thesis proposes a solution how risk-based asset management could be performed practically in a capital-intensive case company in order to optimize the maintenance spending in a long run. Created practical framework is made universal: similar principles can be applied into multiple cases in case company but also in other energy companies. Risk-based asset management`s benefits could be utilized best in portfolio-level optimization where the capital would be invested to the most important objects from total risk point of view. Eventually, such approach would allow case company to optimize capital spending in a situation where funds are not adequate to cover all the mandatory needs and prioritization between the investment alternatives will truly be needed.

Solving large sparse linear systems over the field GF(2)

Nowadays problem of solving sparse linear systems over the field GF(2) remain as a challenge. The popular approach is to improve existing methods such as the block Lanczos method (the Montgomery method) and the Wiedemann-Coppersmith method. Both these methods are considered in the thesis in details: there are their modifications and computational estimation for each process. It demonstrates the most complicated parts of these methods and gives the idea how to improve computations in software point of view. The research provides the implementation of accelerated binary matrix operations computer library which helps to make the progress steps in the Montgomery and in the Wiedemann-Coppersmith methods faster.

A map or chart of the Gulfs of Finland and Livonia with their respective ports and harbours, together with a large Plan of Kroonstad and St. Petersburg, taken from an original drawing lately sent from St. Petersburg

Sold by M. Senex at the Globe over against St. Dunstans Church in Fleetstreet London.

Preparation and Investigation of Bio-coal Mixture Fuels Used in Large Diesel Engines

Coal slurry was of vital interest during the last century due to its potential as an alternative fuel where liquid fuels were necessary. Recently, environmental impacts of the traditional fuels, similarities of bio-coal to that of coal, and huge bio-coal supply has attracted the attention to prepare bio-coal slurries as a new fuel. Rudolf Diesel who invented the diesel engine on 1895 was of the opinion that diesel engines are capable to use different kinds of fuels due to the special design. He tried some kind of vegetable oil to operate on his IC engine. Recently, due to high energy density and more environmentally friendly fuel, researchers believe that bio-coal slurries could act as a new alternative fuel in large diesel engines. Loads of research on different kinds of bio-coal slurry were done by the other researchers worldwide and a lot of progress to boost slurry’s quality were achieved recently. The present study aims to achieve the ideal condition of different factors affecting on the quality of bio-coal slurry. One charcoal sample and two kinds of torrefied wood were used to investigate and compare the reaction of various factors. The results show a great gap between the quality of slurries made of different samples and more researches are necessary to fully understand the impact of the different parameter and improving the quality.