Alpha2-adrenoceptors: Structure and ligand binding properties at the molecular level

Alpha₂-Adrenoceptors: structure and ligand binding properties at the molecular level The mouse is the most frequently used animal model in biomedical research, but the use of zebrafish as a model organism to mimic human diseases is on the increase. Therefore it is considered important to understand their pharmacological differences from humans also at the molecular level. The zebrafish Alpha_2-adrenoceptors were expressed in mammalian cells and the binding affinities of 20 diverse ligands were determined and compared to the corresponding human receptors. The pharmacological properties of the human and zebrafish Alpha_2--adrenoceptors were found to be quite well conserved. Receptor models based on the crystal structures of bovine rhodopsin and the human Beta₂-adrenoceptor revealed that most structural differences between the paralogous and orthologous Alpha_2--adrenoceptors were located within the second extracellular loop (XL2). Reciprocal mutations were generated in the mouse and human Alpha_2--adrenoceptors. Ligand binding experiments revealed that substitutions in XL2 reversed the binding profiles of the human and mouse Alpha_2--adrenoceptors for yohimbine, rauwolscine and RS-79948-197, evidence for a role for XL2 in the determination of species-specific ligand binding. Previous mutagenesis studies had not been able to explain the subtype preference of several large Alpha_2--adrenoceptor antagonists. We prepared chimaeric Alpha_2--adrenoceptors where the first transmembrane (TM1) domain was exchanged between the three human Alpha_2--adrenoceptor subtypes. The binding affinities of spiperone, spiroxatrine and chlorpromazine were observed to be significantly improved by TM1 substitutions of the Alpha_2a--adrenoceptor. Docking simulations indicated that indirect effects, such as allosteric modulation, are more likely to be involved in this phenomenon rather than specific side-chain interactions between ligands and receptors.

Atomic level phenomena on transition metal surfaces

In this study we discuss the atomic level phenomena on transition metal surfaces. Transition metals are widely used as catalysts in industry. Therefore, reactions occuring on transition metal surfaces have large industrial intrest. This study addresses problems in very small size and time scales, which is an important part in the overall understanding of these phenomena. The publications of this study can be roughly divided into two categories: The adsorption of an O2 molecule to a surface, and surface structures of preadsorbed atoms. These two categories complement each other, because in the realistic case there are always some preadsorbed atoms at the catalytically active surfaces. However, all transition metals have an active d-band, and this study is also a study of the in uence of the active d-band on other atoms. At the rst part of this study we discuss the adsorption and dissociation of an O2 molecule on a clean stepped palladium surface and a smooth palladium surface precovered with sulphur and oxygen atoms. We show how the reactivity of the surface against the oxygen molecule varies due to the geometry of the surface and preadsorbed atoms. We also show how the molecular orbitals of the oxygen molecule evolve when it approaches the di erent sites on the surface. In the second part we discuss the surface structures of transition metal surfaces. We study the structures that are intresting on account of the Rashba e ect and charge density waves. We also study the adsorption of suphur on a gold surface, and surface structures of it. In this study we use ab-initio based density functional theory methods to simulate the results. We also compare the results of our methods to the results obtained with the Low-Energy-Electron-Difraction method.

Shared Services at National Level - What, Why, For Whom?

Kristiina Hormia-Poutasen esitys UKSG:n (United Kingdom Serials Group) yhteisiä palveluita käsittelevässä konferenssissa 16.11.2011

Loss Modelling of Three-Level Inverters controlled with Space Vector Modulation Technique

The objective of this master’s thesis is to investigate the loss behavior of three-level ANPC inverter and compare it with conventional NPC inverter. The both inverters are controlled with mature space vector modulation strategy. In order to provide the comparison both accurate and detailed enough NPC and ANPC simulation models should be obtained. The similar control model of SVM is utilized for both NPC and ANPC inverter models. The principles of control algorithms, the structure and description of models are clarified. The power loss calculation model is based on practical calculation approaches with certain assumptions. The comparison between NPC and ANPC topologies is presented based on results obtained for each semiconductor device, their switching and conduction losses and efficiency of the inverters. Alternative switching states of ANPC topology allow distributing losses among the switches more evenly, than in NPC inverter. Obviously, the losses of a switching device depend on its position in the topology. Losses distribution among the components in ANPC topology allows reducing the stress on certain switches, thus losses are equally distributed among the semiconductors, however the efficiency of the inverters is the same. As a new contribution to earlier studies, the obtained models of SVM control, NPC and ANPC inverters have been built. Thus, this thesis can be used in further more complicated modelling of full-power converters for modern multi-megawatt wind energy conversion systems.

The effect of dynamic capabilities on operational-level innovation – Empirical study in magazine publishing industry

This master’s thesis aims to examine the relationship between dynamic capabilities and operational-level innovations. In addition, measures for the concept of dynamic capabilities are developed. The study was executed in the magazine publishing industry which is considered favourable for examining dynamic capabilities, since the sector is characterized by rapid change. As a basis for the study and the measure development, a literary review was conducted. Data for the empirical section was gathered by a survey targeted to chief-editors of Finnish consumer magazines. The relationship between dynamic capabilities and innovation was examined by multiple linear regression. The results indicate that dynamic capabilities have effect on the emergence of radical innovations. Environmental dynamism’s effect on radical innovations was not detected. Also, dynamic capabilities’ effect on innovation was not greater in turbulent operating environment.

Shared and not shared : Providing repository services on a national level

Presentation at the Open Repositories 2012 conference

MASTER DATA MANAGEMENT MATURITY AND TECHNOLOGY ASSESSMENT - From theory to practice, case Ineo Oy

After decades of mergers and acquisitions and successive technology trends such as CRM, ERP and DW, the data in enterprise systems is scattered and inconsistent. Global organizations face the challenge of addressing local uses of shared business entities, such as customer and material, and at the same time have a consistent, unique, and consolidate view of financial indicators. In addition, current enterprise systems do not accommodate the pace of organizational changes and immense efforts are required to maintain data. When it comes to systems integration, ERPs are considered “closed” and expensive. Data structures are complex and the “out-of-the-box” integration options offered are not based on industry standards. Therefore expensive and time-consuming projects are undertaken in order to have required data flowing according to business processes needs. Master Data Management (MDM) emerges as one discipline focused on ensuring long-term data consistency. Presented as a technology-enabled business discipline, it emphasizes business process and governance to model and maintain the data related to key business entities. There are immense technical and organizational challenges to accomplish the “single version of the truth” MDM mantra. Adding one central repository of master data might prove unfeasible in a few scenarios, thus an incremental approach is recommended, starting from areas most critically affected by data issues. This research aims at understanding the current literature on MDM and contrasting it with views from professionals. The data collected from interviews revealed details on the complexities of data structures and data management practices in global organizations, reinforcing the call for more in-depth research on organizational aspects of MDM. The most difficult piece of master data to manage is the “local” part, the attributes related to the sourcing and storing of materials in one particular warehouse in The Netherlands or a complex set of pricing rules for a subsidiary of a customer in Brazil. From a practical perspective, this research evaluates one MDM solution under development at a Finnish IT solution-provider. By means of applying an existing assessment method, the research attempts at providing the company with one possible tool to evaluate its product from a vendor-agnostics perspective.

Evaluating the Maturity of Data Management Practices in a Major Energy Provider Company

Data is the most important asset of a company in the information age. Other assets, such as technology, facilities or products can be copied or reverse-engineered, employees can be brought over, but data remains unique to every company. As data management topics are slowly moving from unknown unknowns to known unknowns, tools to evaluate and manage data properly are developed and refined. Many projects are in progress today to develop various maturity models for evaluating information and data management practices. These maturity models come in many shapes and sizes: from short and concise ones meant for a quick assessment, to complex ones that call for an expert assessment by experienced consultants. In this paper several of them, made not only by external inter-organizational groups and authors, but also developed internally at a Major Energy Provider Company (MEPC) are juxtaposed and thoroughly analyzed. Apart from analyzing the available maturity models related to Data Management, this paper also selects the one with the most merit and describes and analyzes using it to perform a maturity assessment in MEPC. The utility of maturity models is two-fold: descriptive and prescriptive. Besides recording the current state of Data Management practices maturity by performing the assessments, this maturity model is also used to chart the way forward. Thus, after the current situation is presented, analysis and recommendations on how to improve it based on the definitions of higher levels of maturity are given. Generally, the main trend observed was the widening of the Data Management field to include more business and “soft” areas (as opposed to technical ones) and the change of focus towards business value of data, while assuming that the underlying IT systems for managing data are “ideal”, that is, left to the purely technical disciplines to design and maintain. This trend is not only present in Data Management but in other technological areas as well, where more and more attention is given to innovative use of technology, while acknowledging that the strategic importance of IT as such is diminishing.

System-level characterization of Th2 cell development and immune cell responses to ZnO and TiO2 nanoparticles

Asthma and allergy are common diseases and their prevalence is increasing. One of the hypotheses that explains this trend is exposure to inhalable chemicals such as traffi c-related air pollution. Epidemiological research supports this theory, as a correlation between environmental chemicals and allergic respiratory diseases has been found. In addition to ambient airborne particles, one may be exposed to engineered nanosized materials that are actively produced due to their favorable physico-chemical properties compared to their bulk size counterparts. On the cellular level, improper activity of T helper (Th) cells has been connected to allergic reactions. Th cells can differentiate into functionally different effector subsets, which are identifi ed according to their characteristic cytokine profi les resulting in specifi c ability to communicate with other cells. Th2 cells activate humoral immunity and stimulate eradication of extracellular pathogens. However, persistent predominance of Th2 cells is involved in a development of number of allergic diseases. The cytokine environment at the time of antigen recognition is the major factor determining the polarization of a naïve Th cell. Th2 cell differentiation is initiated by IL4, which signals via transcription factor STAT6. Although the importance of this pathway has been evaluated in the mouse studies, the signaling components involved have been largely unknown. The aim of this thesis was to identify molecules, which are under the control of IL4 and STAT6 in Th cells. This was done by using system-level analysis of STAT6 target genes at genome, mRNA and protein level resulting in identifi cation of various genes previously not connected to Th2 cell phenotype acquisition. In the study, STAT6-mediated primary and secondary target genes were dissection from each other and a detailed transcriptional kinetics of Th2 cell polarization of naïve human CD4+ T cells was collected. Integration of these data revealed the hierarchy of molecular events that mediates the differentiation towards Th2 cell phenotype. In addition, the results highlighted the importance of exploiting proteomics tools to complement the studies on STAT6 target genes identifi ed through transcriptional profi ling. In the last subproject, the effects of the exposure with ZnO and TiO2 nanoparticles was analyzed in Jurkat T cell line and in primary human monocyte-derived macrophages and dendritic cells to evaluate their toxicity and potential to cause infl ammation. Identifi cation of ZnO-derived gene expression showed that the same nanoparticles may elicit markedly distinctive responses in different cell types, thus underscoring the need for unbiased profi ling of target genes and pathways affected. The results gave additional proof that the cellular response to nanosized ZnO is due to leached Zn2+ ions. The approach used in ZnO and TiO2 nanoparticle study demonstrated the value of assessing nanoparticle responses through a toxicogenomics approach. The increased knowledge of Th2 cell signaling will hopefully reveal new therapeutic nodes and eventually improve our possibilities to prevent and tackle allergic infl ammatory diseases.

Mathematical modeling of level of anaesthesia from EEG measurements

Problem of modeling of anaesthesia depth level is studied in this Master Thesis. It applies analysis of EEG signals with nonlinear dynamics theory and further classification of obtained values. The main stages of this study are the following: data preprocessing; calculation of optimal embedding parameters for phase space reconstruction; obtaining reconstructed phase portraits of each EEG signal; formation of the feature set to characterise obtained phase portraits; classification of four different anaesthesia levels basing on previously estimated features. Classification was performed with: Linear and quadratic Discriminant Analysis, k Nearest Neighbours method and online clustering. In addition, this work provides overview of existing approaches to anaesthesia depth monitoring, description of basic concepts of nonlinear dynamics theory used in this Master Thesis and comparative analysis of several different classification methods.

Assessment of purchasing maturity in spare parts supply chain

To describe the change of purchasing moving from administrative to strategic function academics have put forward maturity models which help practitioners to compare their purchasing activities to industry top performers and best practices. However, none of the models aim to distinguish the purchasing maturity from the after-sales point of view, even though after-sales activities are acknowledged as a relevant source of revenue, profit and competitive advantage in most manufacturing firms. The maturity of purchasing and supply management practices have a large impact to the overall performance of the spare parts supply chain and ultimately to the value creation and relationship building for the end customer. The research was done as a case study for a European after-sales organization which is part of a globally operating industrial firm specialized in heavy machinery. The study mapped the current state of the purchasing practices in the case organization and also distinguished the relevant areas for future development. The study was based on the purchasing maturity model developed by Schiele (2007) and investigated also how applicable is the maturity model in the spare parts supply chain context. Data for the assessment was gathered using five expert interviews inside the case organization and other parties involved in the company’s spare parts supply chain. Inventory management dimension was added to the original maturity model in order to better capture the important areas in a spare parts supply chain. The added five questions were deduced from the spare parts management literature and verified as relevant areas by the case organization’s personnel. Results indicate that largest need for development in the case organization are: better collaboration between sourcing and operative procurement functions, use of installed base information in the spare parts management, training plan development for new buyers, assessment of aligned KPI’s between the supply chain parties and better defining the role of after-sales sourcing. The purchasing maturity model used in this research worked well in H&R Leading, Controlling and Inventory Management dimensions. The assessment was more difficult to conduct in the Supplier related processes, Process integration and Organizational structure –dimensions, mainly because the assessment in these sections would for some parts require more company-wide assessment. Results indicate also that the purchasing maturity model developed by Schiele (2007) captures the relevant areas in the spare parts supply as well.