Quantitative Analysis of Novel Prostate Cancer Markers in Tissue

Prostate cancer is a heterogeneous disease affecting an increasing number of men all over the world, but particularly in the countries with the Western lifestyle. The best biomarker assay currently available for the diagnosis of the disease, the measurement of prostate specific antigen (PSA) levels from blood, lacks specificity, and even when combined with invasive tests such as digital rectal exam and prostate tissue biopsies, these methods can both miss cancers, and lead to overdiagnosis and subsequent overtreatment of cancers. Moreover, they cannot provide an accurate prognosis for the disease. Due to the high prevalence of indolent prostate cancers, the majority of men affected by prostate cancer would be able to live without any medical intervention. Their latent prostate tumors would not cause any clinical symptoms during their lifetime, but few are willing to take the risk, as currently there are no methods or biomarkers to reliably differentiate the indolent cancers from the aggressive, lethal cases that really are in need of immediate medical treatment. This doctoral work concentrated on validating 12 novel candidate genes for use as biomarkers for prostate cancer by measuring their mRNA expression levels in prostate tissue and peripheral blood of men with cancer as well as unaffected individuals. The panel of genes included the most prominent markers in the current literature: PCA3 and the fusion gene TMPRSS2-ERG, in addition to BMP-6, FGF-8b, MSMB, PSCA, SPINK1, and TRPM8; and the kallikrein-related peptidase genes 2, 3, 4, and 15. Truly quantitative reverse-transcription PCR assays were developed for each of the genes for the purpose, time-resolved fluorometry was applied in the real-time detection of the amplification products, and the gene expression data were normalized by using artificial internal RNA standards. Cancer-related, statistically significant differences in gene transcript levels were found for TMPRSS2-ERG, PCA3, and in a more modest scale, for KLK15, PSCA, and SPINK1. PCA3 RNA was found in the blood of men with metastatic prostate cancer, but not in localized cases of cancer, suggesting limitations for using this method for early cancer detection in blood. TMPRSS2-ERG mRNA transcripts were found more frequently in cancerous than in benign prostate tissues, but they were present also in 51% of the histologically benign prostate tissues of men with prostate cancer, while being absent in specimens from men without any signs of prostate cancer. PCA3 was shown to be 5.8 times overexpressed in cancerous tissue, but similarly to the fusion gene mRNA, its levels were upregulated also in the histologically benign regions of the tissue if the corresponding prostate was harboring carcinoma. These results indicate a possibility to utilize these molecular assays to assist in prostate cancer risk evaluation especially in men with initially histologically negative biopsies.

Forecasting financial weather - can we foresee market sentiment? Quantitative analysis of nodal prices in the New Zealand Electricity Spot Market

Time series of hourly electricity spot prices have peculiar properties. Electricity is by its nature difficult to store and has to be available on demand. There are many reasons for wanting to understand correlations in price movements, e.g. risk management purposes. The entire analysis carried out in this thesis has been applied to the New Zealand nodal electricity prices: offer prices (from 29 May 2002 to 31 March 2009) and final prices (from 1 January 1999 to 31 March 2009). In this paper, such natural factors as location of the node and generation type in the node that effects the correlation between nodal prices have been reviewed. It was noticed that the geographical factor affects the correlation between nodes more than others. Therefore, the visualisation of correlated nodes was done. However, for the offer prices the clear separation of correlated and not correlated nodes was not obtained. Finally, it was concluded that location factor most strongly affects correlation of electricity nodal prices; problems in visualisation probably associated with power losses when the power is transmitted over long distance.

Children at psychiatric risk and their families in Bucharest, in the context of 25 years of changes after December 89’ Romanian Revolution

The aim of the present dissertation was to capture a picture of child and adolescent mental health in Romania, in the context of almost 25 years of changes following the Romanian Revolution of December ’89. A three-part study was carried out in order to provide consistent answers to the pre-defined objectives: to appraise the development of child and adolescent mental health services in Romania (Part I), to explore the characteristics of clinically-referred patients in a Romanian child and adolescent psychiatry department (Part II), to examine the children’s mental health state and its connections with family functioning and associated risk factors (Part III). A multi-method research approach was used, comprising one qualitative analysis and two quantitative research studies. Part I consisted of a comparative qualitative analysis of the answers given by 10 mental health professionals at a 12-questions open ended interview about the current situation in child and adolescent mental health in Romania, on three topics: changes, challenges, solutions. Part II involved a descriptive quantitative analysis of certain variables (e.g. age, gender, primary diagnosis, co-morbidities, time of hospitalization) conducted on the patients who had been admitted to the Child and Adolescent Psychiatry Department at “Prof. Dr. Alexandru Obregia” Psychiatry Hospital, Bucharest in 1991 and in 2013. Part III was conducted on 342 subjects enrolled in two clinical groups and one school group, this study being performed through a cross-sectional analysis on multi-informant child and adolescent mental health problems and competencies (CBCL, YSR, SDQ P, SDQ SR) and their interrelation with household information (HQ) and family functioning (FAD). Outlining the results it can be stated that: 1) The CAMH System in Romania is definitely set on the path of reorganization, including a higher involvement of beneficiaries and of the community. 2) The characteristics of the admitted patients have changed significantly during the last almost 25 years since `89 December Revolution, under the influence of word wide trends in child psychiatry and of administrative aspects of the mental health network in Romania. 3) The rates of main diagnoses and co-morbidities confirm the reports in literature, with Autism Spectrum Disorder being the most frequent childhood psychiatric disorders in this study. 4) The children’s mental health problems in the psychiatry group are comparable to those reported for other clinical populations. 5) Significant score differences were observed according to various household features and also meaningful associations between a child’s clinical status and different aspects of family functioning. The Romanian Child and Adolescent Psychiatry has started to adopt the norms and standards of the European Union. In the 25 years that have elapsed after the 1989 Revolution, many changes have occurred in Romanian CAMH, but many unresolved issues have also risen. Therefore, the major contribution of this thesis is that it provides a coherent and updated overview of the present-day situation from three different perspectives- those of mental healthcare professionals, the one observed in clinical patients and the one reported by children’s families.

Investigation and data adaptive analysis of CARS spectra

In this diploma work advantages of coherent anti-Stokes Raman scattering spectrometry (CARS) and various methods of the quantitative analysis of substance structure with its help are considered. The basic methods and concepts of the adaptive analysis are adduced. On the basis of these methods the algorithm of automatic measurement of a scattering strip size of a target component in CARS spectrum is developed. The algorithm uses known full spectrum of target substance and compares it with a CARS spectrum. The form of a differential spectrum is used as a feedback to control the accuracy of matching. To exclude the influence of a background in CARS spectra the differential spectrum is analysed by means of its second derivative. The algorithm is checked up on the simulated simple spectra and on the spectra of organic compounds received experimentally.

Project and customer profitability analysis: an empirical case study

The objective of this case study is to provide a Finnish solution provider company an objective, in-depth analysis of their project based business and especially of project estimation accuracy. A project and customer profitability analysis is conducted as a complementary addition to describe profitability of the Case Company’s core division. The theoretical framework is constructed on project profitability and customer profitability analysis. Project profitability is approached starting from managing projects, continuing to project pricing process and concluding to project success. The empirical part of this study describes the Case Company’s project portfolio, and by means of quantitative analysis, the study describes how the characteristics of a project impact the project’s profitability. The findings indicate that it really makes a difference in project portfolio’s estimated and actual profitability when methods of installation and technical specifications are scrutinized. Implications on profitability are gathered into a risk assessment tool proposal.

Environmental inFluences on the Adoption of Open Innovation: Analysis of Structural, Institutional and Cultural Impacts

The concept of open innovation has recently gained widespread attention, and is particularly relevant now as many firms endeavouring to implement open innovation, face different sets of challenges associated with managing it. Prior research on open innovation has focused on the internal processes dealing with open innovation implementation and the organizational changes, already taking place or yet required in companies order to succeed in the global open innovation market. Despite the intensive research on open innovation, the question of what influences its adoption by companies in different contexts has not received much attention in studies. To fill this gap, this thesis contribute to the discussion on open innovation influencing factors by bringing in the perspective of environmental impacts, i.e. gathering data on possible sources of external influences, classifying them and testing their systemic impact through conceptual system dynamics simulation model. The insights from data collection and conceptualization in modelling are used to answer the question of how the external environment affects the adoption of open innovation. The thesis research is presented through five research papers reflecting the method triangulation based study (conducted at initial stage as case study, later as quantitative analysis and finally as system dynamics simulation). This multitude of methods was used to collect the possible external influence factors and to assess their impact (on positive/negative scale rather than numerical). The results obtained throughout the thesis research bring valuable insights into understanding of open innovation influencing factors inside a firm’s operating environment, point out the balance required in the system for successful open innovation performance and discover the existence of tipping point of open innovation success when driven by market dynamics and structures. The practical implications on how firms and policy-makers can leverage environment for their potential benefits are offered in the conclusions.

A quantitative view on fuzzy numbers

Since its introduction, fuzzy set theory has become a useful tool in the mathematical modelling of problems in Operations Research and many other fields. The number of applications is growing continuously. In this thesis we investigate a special type of fuzzy set, namely fuzzy numbers. Fuzzy numbers (which will be considered in the thesis as possibility distributions) have been widely used in quantitative analysis in recent decades. In this work two measures of interactivity are defined for fuzzy numbers, the possibilistic correlation and correlation ratio. We focus on both the theoretical and practical applications of these new indices. The approach is based on the level-sets of the fuzzy numbers and on the concept of the joint distribution of marginal possibility distributions. The measures possess similar properties to the corresponding probabilistic correlation and correlation ratio. The connections to real life decision making problems are emphasized focusing on the financial applications. We extend the definitions of possibilistic mean value, variance, covariance and correlation to quasi fuzzy numbers and prove necessary and sufficient conditions for the finiteness of possibilistic mean value and variance. The connection between the concepts of probabilistic and possibilistic correlation is investigated using an exponential distribution. The use of fuzzy numbers in practical applications is demonstrated by the Fuzzy Pay-Off method. This model for real option valuation is based on findings from earlier real option valuation models. We illustrate the use of number of different types of fuzzy numbers and mean value concepts with the method and provide a real life application.

Analysis of testicular cell populations using flow cytometry

Studying testis is complex, because the tissue has a very heterogeneous cell composition and its structure changes dynamically during development. In reproductive field, the cell composition is traditionally studied by morphometric methods such as immunohistochemistry and immunofluorescence. These techniques provide accurate quantitative information about cell composition, cell-cell association and localization of the cells of interest. However, the sample preparation, processing, staining and data analysis are laborious and may take several working days. Flow cytometry protocols coupled with DNA stains have played an important role in providing quantitative information of testicular cells populations ex vivo and in vitro studies. Nevertheless, the addition of specific cells markers such as intracellular antibodies would allow the more specific identification of cells of crucial interest during spermatogenesis. For this study, adult rat Sprague-Dawley rats were used for optimization of the flow cytometry protocol. Specific steps within the protocol were optimized to obtain a singlecell suspension representative of the cell composition of the starting material. Fixation and permeabilization procedure were optimized to be compatible with DNA stains and fluorescent intracellular antibodies. Optimization was achieved by quantitative analysis of specific parameters such as recovery of meiotic cells, amount of debris and comparison of the proportions of the various cell populations with already published data. As a result, a new and fast flow cytometry method coupled with DNA stain and intracellular antigen detection was developed. This new technique is suitable for analysis of population behavior and specific cells during postnatal testis development and spermatogenesis in rodents. This rapid protocol recapitulated the known vimentin and γH2AX protein expression patterns during rodent testis ontogenesis. Moreover, the assay was applicable for phenotype characterization of SCRbKO and E2F1KO mouse models.

Discerning Cultural Depictions and Mistakes in Kafe Piter, a Russian Language Textbook for Finnish Students

This thesis presents the results of an analysis of the content in the series of Russian textbooks Kafe Piter, which is widely used in Finnish educational institutions for adult learners at the time that the research is conducted. The purpose of this study is to determine and describe how a textbook may purvey an image of a foreign country (in this case, Russia). Mixed-methods research with a focus on the qualitative content analysis of Kafe Piter is performed. The guidelines for textbook evaluation of cultural content proposed by Byram (1993) are used in this study as the basis for creating a qualitative analysis checklist, which is adopted according to the needs of the current research. The selection of the categories in the checklist is based on major themes where direct statements about Russia, Russian people and culture appear in the textbook. The cultural content and the way in which it is presented in Kafe Piter are also compared to the intercultural competence objectives of the Common European Framework of Reference for Languages. Because the textbook was not written by a native Russian speaker, it was also important to investigate the types of mistakes found in the books. A simple quantitative analysis in the form of descriptive statistics was done, which consisted of counting the mistakes and inaccuracies in Kafe Piter. The mistakes were categorized into several different groups: factual or cultural, lexicosemantic, grammatical, spelling and punctuation mistakes. Based on the results, the cultural content of Kafe Piter provides a rich variety of cultural information that allows for a good understanding of the Russian language and Russian culture. A sufficient number of cross-cultural elements also appear in the textbook, including cultural images and information describing and comparing Russian and Finnish ways of life. Based on the cultural topics covered in Kafe Piter, we conclude that the textbook is in line with the intercultural competence objectives set out in the Common European Framework of Reference for Languages. The results of the study also make it clear that a thorough proofreading of Kafe Piter is needed in order to correct mistakes - more than 130 cultural and linguistic mistakes and inaccuracies appear in the textbook.

Understanding the bioactivity of plant tannins: developments in analysis methods and structure-activity studies

Tannins, typically segregated into two major groups, the hydrolyzable tannins (HTs) and the proanthocyanidins (PAs), are plant polyphenolic secondary metabolites found throughout the plant kingdom. On one hand, tannins may cause harmful nutritional effects on herbivores, for example insects, and hence they work as plants’ defense against plant-eating animals. On the other hand, they may affect positively some herbivores, such as mammals, for example by their antioxidant, antimicrobial, anti-inflammatory or anticarcinogenic activities. This thesis focuses on understanding the bioactivity of plant tannins, their anthelmintic properties and the tools used for the qualitative and quantitative analysis of this endless source of structural diversity. The first part of the experimental work focused on the development of ultra-high performance liquid chromatography−tandem mass spectrometry (UHPLC-MS/MS) based methods for the rapid fingerprint analysis of bioactive polyphenols, especially tannins. In the second part of the experimental work the in vitro activity of isolated and purified HTs and their hydrolysis product, gallic acid, was tested against egg hatching and larval motility of two larval developmental stages, L1 and L2, of a common ruminant gastrointestinal parasite, Haemonchus contortus. The results indicated clear relationships between the HT structure and the anthelmintic activity. The activity of the studied compounds depended on many structural features, including size, functional groups present in the structure, and the structural rigidness. To further understand tannin bioactivity on a molecular level, the interaction between bovine serum albumin (BSA), and seven HTs and epigallocatechin gallate was examined. The objective was to define the effect of pH on the formation on tannin–protein complexes and to evaluate the stability of the formed complexes by gel electrophoresis and MALDI-TOF-MS. The results indicated that more basic pH values had a stabilizing effect on the tannin–protein complexes and that the tannin oxidative activity was directly linked with their tendency to form covalently stabilized complexes with BSA at increased pH.

Mitä murteita suomessa onkaan? : Murresanaston levikin kvantitatiivista analyysiä

Summary: A quantitative analysis of the distribution of dialect words

KPI definition for measuring customer extranet benefits for a forest company

Tutkimuksen tavoitteena oli määrittää hyötyjä, joita Stora Enso on saavuttanut ottamalla käyttöön extranet-järjestelmän, jonka avulla asiakkaat voivat seurata toimitusketjuaan. Tässä tutkimuksessa keskityttiin taloudellisten hyötyjen määrittämiseen ja aineettomien hyötyjen tutkiminen rajattiintyön ulkopuolelle. Samalla tuli kehittää mittarit itsepalveluasteiden laskemiseksi tietyille toiminnoille, joita asiakkaat voivat hyödyntää järjestelmässä. Myös toiminnot, joita järjestelmässä pääasiassa käytetään, tuli määrittää kvantitatiivisen tutkimuksen avulla. Myyntihenkilöstön haastattelut toimivat apuna laskettaessa taloudellisia hyötyjä. Teoriaosuudessa käsitellään yleisesti sähköisiä palveluita erityisesti yritysten välistä kaupankäyntiä koskevalla alueella. Myös toimitusketjua ja tunnusluku mittareiden rakentamista on esitelty yleisellä tasolla teoriaosassa. Työn keskeisimmät tulokset ovat itsepalveluasteiden mittarit, niiden avulla lasketut itsepalveluasteet sekä taloudelliset hyödyt, joita yrityson saavuttanut järjestelmän käyttöönoton jälkeen.

Asiakaskohtaiseen kannattavuuteen vaikuttavat tekijät paperiteollisuusyrityksessä: empiirinen tutkimus

Tämän tutkimuksen tavoitteena on selvittää asiakaskannattavuuteen vaikuttavat tekijät. Tutkimuksen empiirinen osa käsittelee Stora Enso Publication Papers Kymenlaaksoa. Tutkimusmenetelmänä käytetään kvantitatiivista tutkimusmenetelmää, jossa luodaan tutkimushypoteesit aikaisempien tutkimustulosten perusteella, jonka jälkeen hypoteesit testataan. Aineistona käytetään Stora Enson Fenix-toiminnanohjausjärjestelmästä saatua myynti- ja kustannusdataa. Tutkimustuloksista havaittiin, että tärkein asiakaskannattavuuteen vaikuttava tekijä on myyntihinta, mutta myös kuljetuskustannukset ovat merkittävässä roolissa. Sen sijaan asiakkaankoko tai uskollisuus ei vaikuta kannattavuuteen.

Analyzing dynamic intellectual capital: System-based theory and application

This research report presents an application of systems theory to evaluating intellectual capital (IC) as organization's ability for self-renewal. As renewal ability is a dynamic capability of an organization as a whole, rather than a static asset or an atomistic competence of separate individuals within the organization, it needs to be understood systemically. Consequently, renewal ability has to be measured with systemic methods that are based on a thorough conceptual analysis of systemic characteristics of organizations. The aim of this report is to demonstrate the theory and analysis methodology for grasping companies' systemic efficiency and renewal ability. The volume is divided into three parts. The first deals with the theory of organizations as self-renewing systems. In the second part, the principles of quantitative analysis of organizations are laid down. Finally, the detailed mathematics of the renewal indices are presented. We also assert that the indices produced by the analysis are an effective tool for the management and valuation of knowledge-intensive companies.

Observations on Software Testing Practice

This thesis investigates factors that affect software testing practice. The thesis consists of empirical studies, in which the affecting factors were analyzed and interpreted using quantitative and qualitative methods. First, the Delphi method was used to specify the scope of the thesis. Secondly, for the quantitative analysis 40industry experts from 30 organizational units (OUs) were interviewed. The survey method was used to explore factors that affect software testing practice. Conclusions were derived using correlation and regression analysis. Thirdly, from these 30 OUs, five were further selected for an in-depth case study. The data was collected through 41 semi-structured interviews. The affecting factors and their relationships were interpreted with qualitative analysis using grounded theory as the research method. The practice of software testing was analyzed from the process improvement and knowledge management viewpoints. The qualitative and quantitativeresults were triangulated to increase the validity of the thesis. Results suggested that testing ought to be adjusted according to the business orientation of the OU; the business orientation affects the testing organization and knowledge management strategy, and the business orientation andthe knowledge management strategy affect outsourcing. As a special case, the complex relationship between testing schedules and knowledge transfer is discussed. The results of this thesis can be used in improvingtesting processes and knowledge management in software testing.