Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Transparent Network Interfaces to Mobile Peer-to-Peer Environment

The fact that most of new Personal Data Assistant (PDA) devices and smartphones have the ability to communicate via different wireless technologies has made several new applications possible. While traditional network model is based on the idea of static hosts, mobile devices can create decentralized, self-organizing ad-hoc networks and act as peers in the network. This kind of adapting network is suitable for mobile devices which can freely join and leave the networks. Because several different wireless communication technologies are involved, flexible changing of the networking technology must be handled in order to enable seamless communication between these networks. This thesis presents a transparent network interface to mobile Peer-to-Peer environment which is named as Virtual PeerHood. Different wireless technologies and aspects of providing a seamless connectivity between these technologies are explored. The result is a middleware platform for mobile Peer-to-Peer environment, capable of handling several networking technologies.

Regulation of self-renewal and detection of karyotypic changes of pluripotent human embryonic stem cells

Human embryonic stem cells are pluripotent cells capable of renewing themselves and differentiating to specialized cell types. Because of their unique regenerative potential, pluripotent cells offer new opportunities for disease modeling, development of regenerative therapies, and treating diseases. Before pluripotent cells can be used in any therapeutic applications, there are numerous challenges to overcome. For instance, the key regulators of pluripotency need to be clarified. In addition, long term culture of pluripotent cells is associated with the accumulation of karyotypic abnormalities, which is a concern regarding the safe use of the cells for therapeutic purposes. The goal of the work presented in this thesis was to identify new factors involved in the maintenance of pluripotency, and to further characterize molecular mechanisms of selected candidate genes. Furthermore, we aimed to set up a new method for analyzing genomic integrity of pluripotent cells. The experimental design applied in this study involved a wide range of molecular biology, genome-wide, and computational techniques to study the pluripotency of stem cells and the functions of the target genes. In collaboration with instrument and reagent company Perkin Elmer, KaryoliteTM BoBsTM was implemented for detecting karyotypic changes of pluripotent cells. Novel genes were identified that are highly and specifically expressed in hES cells. Of these genes, L1TD1 and POLR3G were chosen for further investigation. The results revealed that both of these factors are vital for the maintenance of pluripotency and self-renewal of the hESCs. KaryoliteTM BoBsTM was validated as a novel method to detect karyotypic abnormalities in pluripotent stem cells. The results presented in this thesis offer significant new information on the regulatory networks associated with pluripotency. The results will facilitate in understanding developmental and cancer biology, as well as creating stem cell based applications. KaryoliteTM BoBsTM provides rapid, high-throughput, and cost-efficient tool for screening of human pluripotent cell cultures.

Self-deposit, discovery, and delivery of scientific GIS datasets using GeoHydra

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

Printed platforms for paper-based analytical applications

Paper-based analytical technologies enable quantitative and rapid analysis of analytes from various application areas including healthcare, environmental monitoring and food safety. Because paper is a planar, flexible and light weight substrate, the devices can be transported and disposed easily. Diagnostic devices are especially valuable in resourcelimited environments where diagnosis as well as monitoring of therapy can be made even without electricity by using e.g. colorimetric assays. On the other hand, platforms including printed electrodes can be coupled with hand-held readers. They enable electrochemical detection with improved reliability, sensitivity and selectivity compared with colorimetric assays. In this thesis, different roll-to-roll compatible printing technologies were utilized for the fabrication of low-cost paper-based sensor platforms. The platforms intended for colorimetric assays and microfluidics were fabricated by patterning the paper substrates with hydrophobic vinyl substituted polydimethylsiloxane (PDMS) -based ink. Depending on the barrier properties of the substrate, the ink either penetrates into the paper structure creating e.g. microfluidic channel structures or remains on the surface creating a 2D analog of a microplate. The printed PDMS can be cured by a roll-ro-roll compatible infrared (IR) sintering method. The performance of these platforms was studied by printing glucose oxidase-based ink on the PDMS-free reaction areas. The subsequent application of the glucose analyte changed the colour of the white reaction area to purple with the colour density and intensity depending on the concentration of the glucose solution. Printed electrochemical cell platforms were fabricated on paper substrates with appropriate barrier properties by inkjet-printing metal nanoparticle based inks and by IR sintering them into conducting electrodes. Printed PDMS arrays were used for directing the liquid analyte onto the predetermined spots on the electrodes. Various electrochemical measurements were carried out both with the bare electrodes and electrodes functionalized with e.g. self assembled monolayers. Electrochemical glucose sensor was selected as a proof-of-concept device to demonstrate the potential of the printed electronic platforms.

Roll-to-roll atomic layer deposition process for flexible electronics applications

Atomic Layer Deposition (ALD) is the technology of choice where very thin and highquality films are required. Its advantage is its ability to deposit dense and pinhole-free coatings in a controllable manner. It has already shown promising results in a range of applications, e.g. diffusion barrier coatings for OLED displays, surface passivation layers for solar panels. Spatial Atomic Layer Deposition (SALD) is a concept that allows a dramatic increase in ALD throughput. During the SALD process, the substrate moves between spatially separated zones filled with the respective precursor gases and reagents in such a manner that the exposure sequence replicates the conventional ALD cycle. The present work describes the development of a high-throughput ALD process. Preliminary process studies were made using an SALD reactor designed especially for this purpose. The basic properties of the ALD process were demonstrated using the wellstudied Al2O3 trimethyl aluminium (TMA)+H2O process. It was shown that the SALD reactor is able to deposit uniform films in true ALD mode. The ALD nature of the process was proven by demonstrating self-limiting behaviour and linear film growth. The process behaviour and properties of synthesized films were in good agreement with previous ALD studies. Issues related to anomalous deposition at low temperatures were addressed as well. The quality of the coatings was demonstrated by applying 20 nm of the Al2O3 on to polymer substrate and measuring its moisture barrier properties. The results of tests confirmed the superior properties of the coatings and their suitability for flexible electronics encapsulation. Successful results led to the development of a pilot scale roll-to-roll coating system. It was demonstrated that the system is able to deposit superior quality films with a water transmission rate of 5x10-6 g/m2day at a web speed of 0.25 m/min. That is equivalent to a production rate of 180 m2/day and can be potentially increased by using wider webs. State-of-art film quality, high production rates and repeatable results make SALD the technology of choice for manufacturing ultra-high barrier coatings for flexible electronics.

Business intelligence – enabling self-service: A case study in a global manufacturing company

Business intelligence (BI) is an information process that includes the activities and applications used to transform business data into valuable business information. Today’s enterprises are collecting detailed data which has increased the available business data drastically. In order to meet changing customer needs and gain competitive advantage businesses try to leverage this information. However, IT departments are struggling to meet the increased amount of reporting needs. Therefore, recent shift in the BI market has been towards empowering business users with self-service BI capabilities. The purpose of this study was to understand how self-service BI could help businesses to meet increased reporting demands. The research problem was approached with an empirical single case study. Qualitative data was gathered with a semi-structured, theme-based interview. The study found out that case company’s BI system was mostly used for group performance reporting. Ad-hoc and business user-driven information needs were mostly fulfilled with self-made tools and manual work. It was felt that necessary business information was not easily available. The concept of self-service BI was perceived to be helpful to meet such reporting needs. However, it was found out that the available data is often too complex for an average user to fully understand. The respondents felt that in order to self-service BI to work, the data has to be simplified and described in a way that it can be understood by the average business user. The results of the study suggest that BI programs struggle in meeting all the information needs of today’s businesses. The concept of self-service BI tries to resolve this problem by allowing users easy self-service access to necessary business information. However, business data is often complex and hard to understand. Self-serviced BI has to overcome this challenge before it can reach its potential benefits.

Business intelligence – enabling self-service: A case study in a global manufacturing company

Business intelligence (BI) is an information process that includes the activities and applications used to transform business data into valuable business information. Today’s enterprises are collecting detailed data which has increased the available business data drastically. In order to meet changing customer needs and gain competitive advantage businesses try to leverage this information. However, IT departments are struggling to meet the increased amount of reporting needs. Therefore, recent shift in the BI market has been towards empowering business users with self-service BI capabilities. The purpose of this study was to understand how self-service BI could help businesses to meet increased reporting demands. The research problem was approached with an empirical single case study. Qualitative data was gathered with a semi-structured, theme-based interview. The study found out that case company’s BI system was mostly used for group performance reporting. Ad-hoc and business user-driven information needs were mostly fulfilled with self-made tools and manual work. It was felt that necessary business information was not easily available. The concept of self-service BI was perceived to be helpful to meet such reporting needs. However, it was found out that the available data is often too complex for an average user to fully understand. The respondents felt that in order to self-service BI to work, the data has to be simplified and described in a way that it can be understood by the average business user. The results of the study suggest that BI programs struggle in meeting all the information needs of today’s businesses. The concept of self-service BI tries to resolve this problem by allowing users easy self-service access to necessary business information. However, business data is often complex and hard to understand. Self-serviced BI has to overcome this challenge before it can reach its potential benefits.