High-Throughput Screening for Novel Prostate Cancer Drug Targets –Getting Personal

Prostate cancers form a heterogeneous group of diseases and there is a need for novel biomarkers, and for more efficient and targeted methods of treatment. In this thesis, the potential of microarray data, RNA interference (RNAi) and compound screens were utilized in order to identify novel biomarkers, drug targets and drugs for future personalized prostate cancer therapeutics. First, a bioinformatic mRNA expression analysis covering 9873 human tissue and cell samples, including 349 prostate cancer and 147 normal prostate samples, was used to distinguish in silico prevalidated putative prostate cancer biomarkers and drug targets. Second, RNAi based high-throughput (HT) functional profiling of 295 prostate and prostate cancer tissue specific genes was performed in cultured prostate cancer cells. Third, a HT compound screen approach using a library of 4910 drugs and drug-like molecules was exploited to identify potential drugs inhibiting prostate cancer cell growth. Nine candidate drug targets, with biomarker potential, and one cancer selective compound were validated in vitro and in vivo. In addition to androgen receptor (AR) signaling, endoplasmic reticulum (ER) function, arachidonic acid (AA) pathway, redox homeostasis and mitosis were identified as vital processes in prostate cancer cells. ERG oncogene positive cancer cells exhibited sensitivity to induction of oxidative and ER stress, whereas advanced and castrate-resistant prostate cancer (CRPC) could be potentially targeted through AR signaling and mitosis. In conclusion, this thesis illustrates the power of systems biological data analysis in the discovery of potential vulnerabilities present in prostate cancer cells, as well as novel options for personalized cancer management.

Integration in project business : mechanisms for integrating customers and the project network during the life-cycle of industrial projects

This thesis focuses on integration in project business, i.e. how projectbased companies organize their product and process structures when they deliver industrial solutions to their customers. The customers that invest in these solutions run their businesses in different geographical, political and economical environments, which should be acknowledged by the supplier when providing solutions comprising of larger and more complex scopes than previously supplied to these customers. This means that the suppliers are increasing their supply range by taking over some of the activities in the value chain that have traditionally been handled by the customer. In order to be able to provide the functioning solutions, including more engineering hours, technical equipment and a wider project network, a change is needed in the mindset in order to be able to carry out and take the required responsibility that these new approaches bring. For the supplier it is important to be able to integrate technical products, systems and services, but the supplier also needs to have the capabilities to integrate the cross-functional organizations and departments in the project network, the knowledge and information between and within these organizations and departments, along with inputs from the customer into the product and process structures during the lifecycle of the project under development. Hence, the main objective of this thesis is to explore the challenges of integration that industrial projects meet, and based on that, to suggest a concept of how to manage integration in project business by making use of integration mechanisms. Integration is considered the essential process for accomplishing an industrial project, whereas the accomplishment of the industrial project is considered to be the result of the integration. The thesis consists of an extended summary and four papers, that are based on three studies in which integration mechanisms for value creation in industrial project networks and the management of integration in project business have been explored. The research is based on an inductive approach where in particular the design, commissioning and operations functions of industrial projects have been studied, addressing entire project life-cycles. The studies have been conducted in the shipbuilding and power generation industries where the scopes of supply consist of stand-alone equipment, equipment and engineering, and turnkey solutions. These industrial solutions include demanding efforts in engineering and organization. Addressing the calls for more studies on the evolving value chains of integrated solutions, mechanisms for inter- and intra-organizational integration and subsequent value creation in project networks have been explored. The research results in thirteen integration mechanisms and a typology for integration is proposed. Managing integration consists of integrating the project network (the supplier and the sub-suppliers) and the customer (the customer’s business purpose, operations environment and the end-user) into the project by making use of integration mechanisms. The findings bring new insight into research on industrial project business by proposing integration of technology and engineering related elements with elements related to customer oriented business performance in contemporary project environments. Thirteen mechanisms for combining products and the processes needed to deliver projects are described and categorized according to the impact that they have on the management of knowledge and information. These mechanisms directly relate to the performance of the supplier, and consequently to the functioning of the solution that the project provides. This thesis offers ways to promote integration of knowledge and information during the lifecycle of industrial projects, enhancing the development towards innovative solutions in project business.

Developing customer need based services in personal security service industry

The purpose of this thesis is to examine how services can be developed and how the voice of the customer can be incorporated to the strategic planning of services. Furthermore, the objective is to investigate the methods of customer need analysis and service bundling. The data is collected from secondary and primary sources by reviewing the existing academic literature and by conducting in-depth interviews and surveys. The main findings of this research indicate that the service development in personal security service industry should be conducted through a formalized process and the process should begin with setting the strategic objectives. Moreover, the voice of the customer should be incorporated into all stages of the development process, especially into the front-end of the process. Furthermore, the information on customer needs should be gathered in a manner tailored for the purposes of service development.

Adaptação sociocultural do short personal experiences questionnaire (SPEQ) no Brasil

OBJETIVO: traduzir e adaptar culturalmente o Short Personal Experiences Questionnaire (SPEQ) para a língua portuguesa, no Brasil, em mulheres climatéricas. MÉTODOS: a versão original do questionário, em inglês, proveniente da Universidade de Melbourne (Austrália), inicialmente foi traduzida para a língua portuguesa e retraduzida ao inglês. Procedeu-se, então, à adaptação sociocultural do vocabulário e da construção linguística para melhor compreensão. O questionário foi então aplicado para pré-teste em 50 mulheres, em etapas sucessivas, até que não houvesse mais dúvidas. A versão final do instrumento adaptado foi utilizada em estudo de base populacional, autorrespondido anonimamente por 378 mulheres pesquisadas, entre 40 e 65 anos e com 11 anos ou mais de escolaridade, nascidas no Brasil. Foi aplicada uma análise de confiabilidade (consistência interna, pelo alfa de Cronbach), uma análise de validade do construto (correlação de pares de itens que compõem o SPEQ e cada um destes com os quatro fatores obtidos e com o escore total), e uma análise de validade de critério (correlação entre os quatro fatores obtidos com o escore de classificação geral da vida sexual). RESULTADOS: cento e oitenta mulheres responderam a todas as perguntas do SPEQ e foram incluídas na análise. A consistência interna (alfa de Cronbach) para os nove itens do SPEQ situou-se entre 0,55 e 0,77 e o alfa geral foi 0,68. Na análise de validade do construto, a maioria dos coeficientes de correlação se mostrou significativo (valores p<0,005). A análise de validade de critério mostrou coeficientes de correlação significativos em sua maior parte. CONCLUSÕES: a versão em português do instrumento SPEQ, após processo de adaptação, mostrou-se útil e adequada para levantar informações relativas à função sexual e dispareunia em mulheres brasileiras entre 40 e 65 anos e com 11 anos ou mais de escolaridade.

Product placement on personal blogs: a multiple case study from companies’ perspective

As traditional advertising is losing its value in corporations’ marketing, new and growing social media marketing channels are increasing their importance. The growing interest in the media and the lack of research on the subject create a clear need for this study. The objectives are to increase understanding about product placement in personal blogs and examine the benefits as well as the downsides created by this marketing channel and present the requirements for success. The study also takes a stand on what kind of things a successful product placement strategy in personal blogs includes and what points should be considered when creating a strategy. The study’s empirical part consists of seven thematic interviews with case companies’ representatives and one agent. The study’s personal blogs were delimited to consist only lifestyle and fashion blogs. The results show that product placement on personal lifestyle and fashion blogs is a strongly growing marketing channel and it is best suited to reach young women. It is also a very good channel to change and improve brand image. Via personal blogs it is possible to reach a large number of consumers with a very cost-efficient manner. Thus utilizing the channel is suitable for all companies regardless of the size of the marketing budget. Of course, companies have to consider the suitability of their product to the themes of blogs. Executing a successful campaign in this media requires good relationship management skills and understanding of this particular media as the final content is not in advertiser’s hands. As a marketing channel, personal blogs differ highly from traditional marketing channels because of their constantly changing nature and multidirectional quality where several parties are in interaction.

Gamification as a means for employee motivation, personal engagement and behavioral outcomes: a gamification system developers’ perspective

A major challenge faced by companies today is the engagement gap at the workplace and how to motivate employees to engage in less intrinsically motivating work activities that are valuable for the organization. The objective of this study is to investigate gamification as a means for employee motivation and personal engagement that result in behavioral outcomes from the gamification developers’ perspective. Theories of work motivation and engagement are viewed in relation to gamification. The empirical part conducts a qualitative multiple-case study. The data is analyzed with the CAQDAS NVivo. The empirical findings suggest that gamification can enhance employee motivation, but careful consideration of extrinsic motivators is necessary to avoid their detrimental effect on intrinsic motivation. Employee self-determination is built through internalization of gamified system’s goals reaching autonomous motivation to engage in the target behavior. Employee engagement is built by fulfilling the psychological conditions of meaningfulness, safety and availability. The results suggest that gamification can build employee motivation and engagement leading to behavior change if designed with the business objectives in mind. Moreover, the gamified system needs to be renewed to address the changes in the business environment and reflect them in the employee behavior.

Chemical derivatization of galactoglucomannan for functional materials

In the framework of the biorefinery concept researchers aspire to optimize the utilization of plant materials, such as agricultural wastes and wood. For most of the known processes, the first steps in the valorisation of biomass are the extraction and purification of the individual components. The obtained raw products by means of a controlled separation can consecutively be modified to result in biofuels or biogas for energy production, but also in value-added products such as additives and important building blocks for the chemical and material industries. Considerable efforts are undertaken in order to substitute the use of oil-based starting materials or at least minimize their processing for the production of everyday goods. Wood is one of the raw materials, which have gained large attention in the last decades and its composition has been studied in detail. Nowadays, the extraction of water-soluble hemicelluloses from wood is well known and so for example xylan can be obtained from hardwoods and O-acetyl galactoglucomannans (GGMs) from softwoods. The aim of this work was to develop water-soluble amphiphilic materials of GGM and to assess their potential use as additives. Furthermore, GGM was also applied as a crosslinker in the synthesis of functional hydrogels for the removal of toxic metals and metalloid ions from aqueous solutions. The distinguished products were obtained by several chemical approaches and analysed by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), size exclusion chromatography (SEC), thermal gravimetric analysis (TGA), scanning electron microscope SEM, among others. Bio-based surfactants were produced by applying GGM and different fatty acids as starting materials. On one hand, GGM-grafted-fatty acids were prepared by esterification and on the other hand, well-defined GGM-block-fatty acid derivatives were obtained by linking amino-functional fatty acids to the reducing end of GGM. The reaction conditions for the syntheses were optimized and the resultant amphiphilic GGM derivatives were evaluated concerning their ability to reduce the surface tension of water as surfactants. Furthermore, the block-structured derivatives were tested in respect to their applicability as additives for the surface modification of cellulosic materials. Besides the GGM surfactants with a bio-based hydrophilic and a bio-based hydrophobic part, also GGM block-structured derivatives with a synthetic hydrophobic tail, consisting of a polydimethylsiloxane chain, were prepared and assessed for the hydrophobization of surface of nanofibrillated cellulose films. In order to generate GGM block-structured derivatives containing a synthetic tail with distinguished physical and chemical properties, as well as a tailored chain length, a controlled polymerization method was used. Therefore, firstly an initiator group was introduced at the reducing end of the GGM and consecutively single electron transfer-living radical polymerization (SET-LRP) was performed by applying three different monomers in individual reactions. For the accomplishment of the synthesis and the analysis of the products, challenges related to the solubility of the reactants had to be overcome. Overall, a synthesis route for the production of GGM block-copolymers bearing different synthetic polymer chains was developed and several derivatives were obtained. Moreover, GGM with different molar masses were, after modification, used as a crosslinker in the synthesis of functional hydrogels. Hereby, a cationic monomer was used during the free radical polymerization and the resultant hydrogels were successfully tested for the removal of chromium and arsenic ions from aqueous solutions. The hydrogel synthesis was tailored and materials with distinguished physical properties, such as the swelling rate, were obtained after purification. The results generated in this work underline the potential of bio-based products and the urge to continue carrying out research in order to be able to use more green chemicals for the manufacturing of biorenewable and biodegradable daily products.

Spot urine porphyrins/creatinine ratio profile of healthy Brazilian individuals adjusted for personal habits

Changes in urinary porphyrin excretion may be the result of hereditary causes and/or from environmental or occupational exposure. The objective of this study was to measure the amount of some porphyrins in spot urine samples obtained from volunteers randomly selected from a healthy adult population of São Paulo with a sensitive HPLC method and to estimate normal ranges for a non-exposed population. Spot urine samples were collected from 126 subjects (both genders, 18 to 65 years old) not occupationally exposed to porphyrinogenic agents. Porphyrin fractions were separated on RP-18 HPLC column eluted with a methanol/ammonium acetate buffer gradient, pH 4.0, and measured fluorometrically (excitation 405 nm/emission 620 nm). The amount of porphyrins was corrected for urinary creatinine excretion. Only 8-carboxyl (uro) and 4-carboxyl (copro) porphyrins were quantified as µg/g creatinine. Data regarding age, gender, occupational activities, smoking and drinking habits were analyzed by Mann-Whitney and Kruskal-Wallis tests. Uroporphyrin results did not differ significantly between the subgroups studied. Copro and uro + copro porphyrins were significantly different for smokers (P = 0.008) and occupational activities (P = 0.004). With respect to alcohol consumption, only men drinking >20 g/week showed significant differences in the levels of copro (P = 0.022) and uro + copro porphyrins (P = 0.012). The 2.5-97.5th percentile limit values, excluding those for subjects with an alcohol drinking habit >20 g/week, were 0-20.8, 11.7-93.1, and 15.9-102.9 µg/g creatinine for uro, copro and uro + copro porphyrins, respectively. These percentile limit values can be proposed as a first attempt to provide urinary porphyrin reference values for our population, serving for an early diagnosis of porphyrinopathies or as biomarkers of exposure to porphyrinogenic agents.

Personal branding on social media - The characteristics of strong personal brands in Finland

The purpose of the study is to define the characteristics of strong personal brands on social media in Finland. Personal branding as a phenomenon is no longer limited to celebrities and political leaders. The digital revolution and the change in online behavior have created the need for a deeper investigation of the characteristics of strong personal brands on social media. The work of different academics on personal branding are examined to gain a comprehensive understanding on this research topic that has gone through a revolution during the last decade. Early impression management theory is refined to include elements from more modern literature related to personal branding, brand identity management and social media to create a theoretical framework that simplifies the process of personal brand building on social media. The framework consisting of three phases clarifies the process of modern personal branding. The results of the study are presented in line with three research themes derived from the theoretical framework: the background of the brand, the brand identity management and the social media behavior and activities. Mixed methods are used in the research as means to broaden perception on the subject. The quantitative part of the study defines general characteristics concerning the most follower personal brands in Finland in three social media channels – Facebook, Instagram and Twitter. The other part of the research was conducted by single case study including two Finnish personal brands cases to provide a deeper understanding of personal branding practices of strong social media personal brands. The results of the study show that the most used social media channels differ in terms of the personal brand characteristics and personal branding activities. Due to the characteristics of the channels also the post activities of the personal brands differ quite significantly. It can be also inferred that there is a difference between brands with an existing offline awareness and the brands with no awareness before joining the social media. In order to reduce the gap between the ideal brand image and the current image, the brand should have a clear vision as well as a good understanding of the target group and the value it creates for its target audience. The brand identity needs to be managed by communicating with the target audience authentically in the right channels, with relevant content. The dedication, the target group’s behavior and the ability to create valuable and relevant content determines the right tactics for social media personal branding.  

Ser organizado aumenta tu efectividad personal y laboral. Documento de preguntas y respuestas

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