JNK regulates dendrite and spine architecture in the central nervous system influencing spatial learning and motor tasks

JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.

Behavioral Responses in Mice Selectively Bred for High and Low Levels of Open-Field Thigmotaxis

In animal psychology, the open-field (OF) test is a traditional method for studying different aspects of rodent behavior, with thigmotaxis (i.e., wallseeking behavior) being one of the best validated OF parameters employed to measure emotionality. The main purpose of the present study was to investigate the selection response in mice selectively bred for high and low levels of OF thigmotaxis (the HOFT and LOFT lines, respectively). The mice (N = 2048) were selected for 23 generations, resulting in bidirectional phenotypic divergence between the two lines; that is, the HOFT mice were more thigmotactic (i.e., more emotional) than the LOFT mice across the different generations. The origin of the line difference in thigmotaxis was further investigated by using the crossfostering paradigm, with the results suggesting that the divergence between the two lines was primarily innate in origin and not influenced by differing maternal behavior. The stability of the selection trait was examined by testing the animals at different ages as well as in varying conditions. The results indicated that the line difference in thigmotaxis was not affected by age at the time of testing, and it also persisted in the different OF testing situations as well as during pregnancy and lactation. The examination of a possible coselection of other characteristics revealed that the more thigmotactic HOFT mice lived longer than the less thigmotactic LOFT mice. In addition, the HOFT mice tended to rear and explore less than the LOFT mice, supporting the general assumption that emotionality and exploration are inversely related. The two lines did not generally differ in ambulation and defecation, that is, in the traditional OF indexes of emotionality, conforming to the suggestion that emotionality is a multidimensional construct. The effects of sex on different OF parameters were also assessed, with the results suggesting that among the HOFT and LOFT lines, the female mice were more emotional than the male mice. The examination of the temporal changes in the HOFT and LOFT lines’ OF behavior revealed some contradictory findings that also partially conflicted with general assumptions. Although this study did not show prominent differences in maternal responsiveness between the HOFT and LOFT mothers, the results suggested that the line divergence in emotionality was more pronounced in the presence of a pup after parturition than during pregnancy. The present study clearly demonstrates that OF thigmotaxis is a strong characteristic for producing two diverging lines of mice. The difference in thigmotaxis between the selectively bred HOFT and LOFT mice seemed to be a stable and robust feature of these animals, and it appeared to stem from a genetic background.

Evaluating multidimensional visualization techniques in data mining tasks

Visual data mining (VDM) tools employ information visualization techniques in order to represent large amounts of high-dimensional data graphically and to involve the user in exploring data at different levels of detail. The users are looking for outliers, patterns and models – in the form of clusters, classes, trends, and relationships – in different categories of data, i.e., financial, business information, etc. The focus of this thesis is the evaluation of multidimensional visualization techniques, especially from the business user’s perspective. We address three research problems. The first problem is the evaluation of projection-based visualizations with respect to their effectiveness in preserving the original distances between data points and the clustering structure of the data. In this respect, we propose the use of existing clustering validity measures. We illustrate their usefulness in evaluating five visualization techniques: Principal Components Analysis (PCA), Sammon’s Mapping, Self-Organizing Map (SOM), Radial Coordinate Visualization and Star Coordinates. The second problem is concerned with evaluating different visualization techniques as to their effectiveness in visual data mining of business data. For this purpose, we propose an inquiry evaluation technique and conduct the evaluation of nine visualization techniques. The visualizations under evaluation are Multiple Line Graphs, Permutation Matrix, Survey Plot, Scatter Plot Matrix, Parallel Coordinates, Treemap, PCA, Sammon’s Mapping and the SOM. The third problem is the evaluation of quality of use of VDM tools. We provide a conceptual framework for evaluating the quality of use of VDM tools and apply it to the evaluation of the SOM. In the evaluation, we use an inquiry technique for which we developed a questionnaire based on the proposed framework. The contributions of the thesis consist of three new evaluation techniques and the results obtained by applying these evaluation techniques. The thesis provides a systematic approach to evaluation of various visualization techniques. In this respect, first, we performed and described the evaluations in a systematic way, highlighting the evaluation activities, and their inputs and outputs. Secondly, we integrated the evaluation studies in the broad framework of usability evaluation. The results of the evaluations are intended to help developers and researchers of visualization systems to select appropriate visualization techniques in specific situations. The results of the evaluations also contribute to the understanding of the strengths and limitations of the visualization techniques evaluated and further to the improvement of these techniques.

Performance Comparison of Behavioral Finance -based Investment Strategies in the Finnish Stock Market 1996-2010

In this thesis traditional investment strategies (value and growth) are compared to modern investment strategies (momentum, contrarian and GARP) in terms of risk, performance and cumulative returns. Strategies are compared during time period reaching from 1996 to 2010 in the Finnish stock market. Used data includes all listed main list stocks, dividends and is adjusted in case of splits, and mergers and acquisitions. Strategies are tested using different holding periods (6, 12 and 36 months) and data is divided into tercile portfolios based on different ranking criteria. Contrarian and growth strategies are the only strategies with improved cumulative returns when longer holding periods are used. Momentum (52-week high price1) and GARP strategies based on short holding period have the best performance and contrarian and growth strategies the worst. Momentum strategies (52-week high price) along with short holding period contrarian strategies (52-week low price2) have the lowest risk. Strategies with the highest risk are both growth strategies and two momentum strategies (52-week low price). The empirical results support the efficiency of momentum, GARP and value strategies. The least efficient strategies are contrarian and growth strategies in terms of risk, performance and cumulative returns. Most strategies outperform the market portfolio in all three measures. 1 Stock ranking criterion (current price/52-week highest price) 2 Stock ranking criterion (current price/52-week lowest price)

The Effects of Service Quality, Customer Satisfaction and Customer Perceived Value on Behavioral Intentions

The intent of this research was to develop a model that describes the extent to which customer behavioral intentions are influenced by service quality, customer satisfaction and customer perceived value in the business-to-business service context. Research on customer behavioral intentions is quite fragmented and no generalized model has been presented. Thus, there was need for empirical testing. This study builds on the services marketing theory and assesses the relationships between the identified constructs. The data for the empirical analysis was collected via a quantitative online survey and a total of 226 usable responses were obtained for further analysis. The model was tested in an employment agency service setting. The measures used in this survey were first assessed by using confirmatory factor analysis (CFA) after which the hypothesized relationships were further verified using structural equation modeling (SEM) in LISREL 8.80. The analysis identified that customer satisfaction played a pivotal role in the model as it was the only direct antecedent of customer behavioral intentions, however, customer perceived value showed a strong indirect impact on buying intentions via customer satisfaction. In contrast to what was hypothesized, service quality and customer perceived value did not have a direct positive effect on behavioral intentions. Also, a contradicting finding with current literature was that sacrifice was argued to have a direct but positive impact on customer perceived value. Based on the findings in this study, managers should carefully think of their service strategies that lead to their customers’ favorable behavioral intentions.

Training executive functions in the laboratory and in real life : cognitive consequences of computer-based exercises and bilingualism

The question of the trainability of executive functions and the impact of such training on related cognitive skills has stirred considerable research interest. Despite a number of studies investigating this, the question has not yet been solved. The general aim of this thesis was to investigate two very different types of training of executive functions: laboratory-based computerized training (Studies I-III) and realworld training through bilingualism (Studies IV-V). Bilingualism as a kind of training of executive functions is based on the idea that managing two languages requires executive resources, and previous studies have suggested a bilingual advantage in executive functions. Three executive functions were studied in the present thesis: updating of working memory (WM) contents, inhibition of irrelevant information, and shifting between tasks and mental sets. Studies I-III investigated the effects of computer-based training of WM updating (Study I), inhibition (Study II), and set shifting (Study III) in healthy young adults. All studies showed increased performance on the trained task. More importantly, improvement on an untrained task tapping the trained executive function (near transfer) was seen in Study I and II. None of the three studies showed improvement on untrained tasks tapping some other cognitive function (far transfer) as a result of training. Study I also used PET to investigate the effects of WM updating training on a neurotransmitter closely linked to WM, namely dopamine. The PET results revealed increased striatal dopamine release during WM updating performance as a result of training. Study IV investigated the ability to inhibit task-irrelevant stimuli in bilinguals and monolinguals by using a dichotic listening task. The results showed that the bilinguals exceeded the monolinguals in inhibiting task-irrelevant information. Study V introduced a new, complementary research approach to study the bilingual executive advantage and its underlying mechanisms. To circumvent the methodological problems related to natural groups design, this approach focuses only on bilinguals and examines whether individual differences in bilingual behavior correlate with executive task performances. Using measures that tap the three above-entioned executive functions, the results suggested that more frequent language switching was associated with better set shifting skills, and earlier acquisition of the second language was related to better inhibition skills. In conclusion, the present behavioral results showed that computer-based training of executive functions can improve performance on the trained task and on closely related tasks, but does not yield a more general improvement of cognitive skills. Moreover, the functional neuroimaging results reveal that WM training modulates striatal dopaminergic function, speaking for training-induced neural plasticity in this important neurotransmitter system. With regard to bilingualism, the results provide further support to the idea that bilingualism can enhance executive functions. In addition, the new complementary research approach proposed here provides some clues as to which aspects of everyday bilingual behavior may be related to the advantage in executive functions in bilingual individuals.

Brand attitudes influence on city brand image, and their impact on behavioral intention

The main objective of this Master’s Thesis was to examine the perceived city brand image of tourists and residents. It was aimed to accomplish by examining first the contribution of city attributes and marketing communications on forming brand attitudes, and then discover how the brand attitudes influence on city brand image. The impact of brand attitudes and city brand image on behavioral intention was also reviewed. The empirical part of the thesis was conducted with a quantitative method through online-based survey. The sample (n = 492) consisted of tourists and residents of the case city. The data was analyzed with statistical analyses by SPSS program. Brand attitudes, based on the main attributes, were calculated through multi-attribute attitude model. The results confirmed exposure to marketing communications has direct and positive influence on brand attitudes, especially the offline marketing communications. The findings revealed brand attitudes impact directly on city brand image perception. Brand attitudes and brand image dimensions had direct impact on tourists and residents’ behavioral intention. The findings provide important information for the city marketers. They increase marketers understanding on how target population perceives the city brand image and how it impacts on their future behavior. This thesis reveals the perception of current city brand image and gives guidance on what to emphasize in city branding to increase city’s attractiveness in conjunction with its economic development. Furthermore, the created framework can be utilized also in the future researches.

Design and validation of stateful composite RESTful web services

A web service is a software system that provides a machine-processable interface to the other machines over the network using different Internet protocols. They are being increasingly used in the industry in order to automate different tasks and offer services to a wider audience. The REST architectural style aims at producing scalable and extensible web services using technologies that play well with the existing tools and infrastructure of the web. It provides a uniform set of operation that can be used to invoke a CRUD interface (create, retrieve, update and delete) of a web service. The stateless behavior of the service interface requires that every request to a resource is independent of the previous ones facilitating scalability. Automated systems, e.g., hotel reservation systems, provide advanced scenarios for stateful services that require a certain sequence of requests that must be followed in order to fulfill the service goals. Designing and developing such services for advanced scenarios with REST constraints require rigorous approaches that are capable of creating web services that can be trusted for their behavior. Systems that can be trusted for their behavior can be termed as dependable systems. This thesis presents an integrated design, analysis and validation approach that facilitates the service developer to create dependable and stateful REST web services. The main contribution of this thesis is that we provide a novel model-driven methodology to design behavioral REST web service interfaces and their compositions. The behavioral interfaces provide information on what methods can be invoked on a service and the pre- and post-conditions of these methods. The methodology uses Unified Modeling Language (UML), as the modeling language, which has a wide user base and has mature tools that are continuously evolving. We have used UML class diagram and UML state machine diagram with additional design constraints to provide resource and behavioral models, respectively, for designing REST web service interfaces. These service design models serve as a specification document and the information presented in them have manifold applications. The service design models also contain information about the time and domain requirements of the service that can help in requirement traceability which is an important part of our approach. Requirement traceability helps in capturing faults in the design models and other elements of software development environment by tracing back and forth the unfulfilled requirements of the service. The information about service actors is also included in the design models which is required for authenticating the service requests by authorized actors since not all types of users have access to all the resources. In addition, following our design approach, the service developer can ensure that the designed web service interfaces will be REST compliant. The second contribution of this thesis is consistency analysis of the behavioral REST interfaces. To overcome the inconsistency problem and design errors in our service models, we have used semantic technologies. The REST interfaces are represented in web ontology language, OWL2, that can be part of the semantic web. These interfaces are used with OWL 2 reasoners to check unsatisfiable concepts which result in implementations that fail. This work is fully automated thanks to the implemented translation tool and the existing OWL 2 reasoners. The third contribution of this thesis is the verification and validation of REST web services. We have used model checking techniques with UPPAAL model checker for this purpose. The timed automata of UML based service design models are generated with our transformation tool that are verified for their basic characteristics like deadlock freedom, liveness, reachability and safety. The implementation of a web service is tested using a black-box testing approach. Test cases are generated from the UPPAAL timed automata and using the online testing tool, UPPAAL TRON, the service implementation is validated at runtime against its specifications. Requirement traceability is also addressed in our validation approach with which we can see what service goals are met and trace back the unfulfilled service goals to detect the faults in the design models. A final contribution of the thesis is an implementation of behavioral REST interfaces and service monitors from the service design models. The partial code generation tool creates code skeletons of REST web services with method pre and post-conditions. The preconditions of methods constrain the user to invoke the stateful REST service under the right conditions and the post condition constraint the service developer to implement the right functionality. The details of the methods can be manually inserted by the developer as required. We do not target complete automation because we focus only on the interface aspects of the web service. The applicability of the approach is demonstrated with a pedagogical example of a hotel room booking service and a relatively complex worked example of holiday booking service taken from the industrial context. The former example presents a simple explanation of the approach and the later worked example shows how stateful and timed web services offering complex scenarios and involving other web services can be constructed using our approach.

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.

What do Sports Sponsors Really Want? The effects of service quality, service value and customer satisfaction on behavioral intentions in sports sponsorship context

The aim of this Master’s thesis was to study the antecedents of customer satisfaction and behavioral intentions and their relative relationships in the sports sponsorship context. The possible antecedents under investigation in the current research are service value and service quality. As the academic background in the sports sponsorship literature is still rather modest there was a need for further empirical testing. The theoretical part of the research builds on the existing services marketing literature with sports sponsorship and business-to-business contexts in mind. The empirical study focused on the case company Liiga-SaiPa Oy. The data for the empirical analysis was collected via quantitative online survey. The total sample consisted of 357 the case company’s business customers and a total of 80 usable responses were collected. The data was analyzed by using statistical analysis software, SPSS. According to the results of the empirical analysis the most important antecedent of behavioral intentions in the underlying context is customer satisfaction. Also service value was found to have a direct and positive relationship with behavioral intentions. Moreover no indirect relationships through satisfaction were found between service quality and service value and behavioral intentions. However both constructs of service value and service quality were diagnosed to have a direct and positive effect on customer satisfaction. Service quality was also found to be a direct antecedent of service value with other service value benefits. However a contradicting finding with the current literature was, that service value sacrifices were not found to have a significant relationship with overall service value perceptions.

Visual analytics for behavioral and niche market segmentation

Companies require information in order to gain an improved understanding of their customers. Data concerning customers, their interests and behavior are collected through different loyalty programs. The amount of data stored in company data bases has increased exponentially over the years and become difficult to handle. This research area is the subject of much current interest, not only in academia but also in practice, as is shown by several magazines and blogs that are covering topics on how to get to know your customers, Big Data, information visualization, and data warehousing. In this Ph.D. thesis, the Self-Organizing Map and two extensions of it – the Weighted Self-Organizing Map (WSOM) and the Self-Organizing Time Map (SOTM) – are used as data mining methods for extracting information from large amounts of customer data. The thesis focuses on how data mining methods can be used to model and analyze customer data in order to gain an overview of the customer base, as well as, for analyzing niche-markets. The thesis uses real world customer data to create models for customer profiling. Evaluation of the built models is performed by CRM experts from the retailing industry. The experts considered the information gained with help of the models to be valuable and useful for decision making and for making strategic planning for the future.