867 resultados para key factors
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The Early Cretaceous has experienced the development of large shallow-water carbonate platform in tropical and subtropical regions, favoured by exceptionally warm climatic conditions, optimal trophic conditions and a suitable tectonic and paleogeographic context. This period was also characterized by shorter intervals, in which the widespread deposition of marine sediments enriched in organic matter occurred ("oceanic anoxic episodes": OAE). This study focuses on the Barremian- Aptian interval, during which the Urgonian platform developed throughout the northern Tethyan passive margin. Due to the Alpine orogeny, sediments belonging to this platform - named locally Schrattenkalk Formation, are presently outcropping in the Helvetic Alps. This study aims to reconstruct the paleogeographic evolution of the Helvetic platform, and to define the environmental and oceanographic factors, which influenced its development. Several key episodes in the life of this platform have been identified: - The installation of the platform, covering hemipelagic sediments of the Drusberg Member, near the limit between the early and late Barremian. - The temporary change of carbonate production type during the basal Aptian, with the deposition of the Rawil Member. - And finally the definitive interruption of photozoan carbonate platform sedimentation in the study area, during the early Aptian. The sedimentological, biostratigraphical and chemostratigraphic (8I3C) data lead to the sequential subdivision of eleven sections and one core, located throughout the different Helvetic nappes of Switzerland. The sequence stratigraphie framework, initially defined for the Urgonian carbonate platform of the Vercors area (SE France), is confirmed in the Helvetic nappes, where the same number of sequences was observed. Many similarities between these two areas are put forward in this work. The sequence stratigraphie framework helped to highlight the installation of a bioclastic body, included in the Schrattenkalk Formation, since the middle Early Barremian (sequence B2). The age of the installation of the rudist-rich limestone, which corresponds to the Urgonian facies sensu stricto, is attributed to the late Barremian (maximum flooding surface of the sequence B3). This age coincides with the one determined in other northern Tethyan areas for the installation of the Urgonian platform. The results of this study show a strong tectonic control of the platform architecture, with the presence of syn-sedimentary faults in a perpendicular position to the progradation direction of the platform. The presence of these faults was highlighted by the study of the evolution of the microfacies distribution and by thickness variations in different areas. Sea level fluctuations also played an important role in the various life phases of the platform. Three major falls in sea level have been identified. A significant emersion of the proximal domain has been observed, involving an important drop of the relative sea level, leading to the exposure of the Drusberg Member hemipelagic series. A second major drop in sea level is identified near the Barremian-Aptian boundary, and a third is registered on the top of the Upper Schrattenkalk Member on the whole platform; it is associated with a karst affecting the underlying limestones to a depth of over 20 meters. This observation sheds new light on the conditions linked to the demise of Urgonian platform, which was strongly influenced by this phase of emersion.
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Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
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Molecular Characteristics of Neuroblastoma with Special Reference to Novel Prognostic Factors and Diagnostic Applications Department of Medical Biochemistry and Genetics Annales Universitatis Turkuensis, Medica-Odontologica, 2009, Turku, Finland Painosalama Oy, Turku, Finland 2009 Background: Neuroblastoma, which is the most common and extensively studied childhood solid cancer, shows a great clinical and biological heterogeneity. Most of the neuroblastoma patients older than one year have poor prognosis despite intensive therapies. The hallmark of neuroblastoma, biological heterogeneity, has hindered the discovery of prognostic tumour markers. At present, few molecular markers, such as MYCN oncogene status, have been adopted into clinical practice. Aims: The aim of the study was to improve the current prognostic methodology of neuroblastoma, especially by taking cognizance of the biological heterogeneity of neuroblastoma. Furthermore, unravelling novel molecular characteristics which associate with neuroblastoma tumour progression and cell differentiation was an additional objective. Results: A new strictly defined selection of neuroblastoma tumour spots of highest proliferation activity, hotspots, appeared to be representative and reliable in an analysis of MYCN amplification status using a chromogenic in situ hybridization technique (CISH). Based on the hotspot tumour tissue microarray immunohistochemistry and high-resolution oligo-array-based comparative genomic hybridization, which was integrated with gene expression and in silico analysis of existing transcriptomics, a polysialylated neural cell adhesion molecule (NCAM) and poorly characterized amplicon at 12q24.31 were discovered to associate with outcome. In addition, we found that a previously considered new neuroblastoma treatment target, the mutated c-kit receptor, was not mutated in neuroblastoma samples. Conclusions: Our studies indicate polysialylated NCAM and 12q24.31 amplicon to be new molecular markers with important value in prognostic evaluation of neuroblastoma. Moreover, the presented hotspot tumour tissue microarray method together with the CISH technique of the MYCN oncogene copy number is directly applicable to clinical use. Key words: neuroblastoma, polysialic acid, neural cell adhesion molecule, MYCN, c-kit, chromogenic in situ hybridization, hotspot
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More and more companies are interested in implementing knowledge management. However, the majority of knowledge management initiatives will fail to have any significant impact. In this study, theories regarding knowledge management implementation and adoption are investigated further. The objective of this study is to deepen understanding regarding the critical factors that contribute to successful knowledge management adoption in large multinational companies. The study is formulated around the following four research questions: 1. What are the key success and failure factors in knowledge management implementation? 2. How can knowledge management adoption be improved at the individual, group and organizational levels of the company? 3. What are the critical factors that hinder knowledge management adoption in the case company? 4. How can the case company promote the adoption of knowledge management among company personnel? The methodology used in this study is a combination of a literature review and an explanatory, exploratory, qualitative single-case study. The literature review answers the first and second research questions. Based on the literature review, a framework is presented to illustrate the factors contributing to the success of knowledge management implementation. The framework also links together knowledge management implementation and adoption. The third research question is answered by revealing the relevant findings from 21 expert interviews and 2 online questionnaires with 42 respondents in total. By comparing and contrasting the results of the literature review with the findings of the empirical case study, the fourth research question is answered. The concrete outcomes of this study are a framework to elucidate the factors contributing to the success of knowledge management implementation, a case study highlighting the issues that hinder knowledge management adoption within the case company, and recommendations for the case company.
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Chironomidae spatial distribution was investigated at 63 near-pristine sites in 22 catchments of the Iberian Mediterranean coast. We used partial redundancy analysis to study Chironomidae community responses to a number of environmental factors acting at several spatial scales. The percentage of variation explained by local factors (23.3%) was higher than that explained by geographical (8.5%) or regional factors(8%). Catchment area, longitude, pH, % siliceous rocks in the catchment, and altitude were the best predictors of Chironomidae assemblages. We used a k-means cluster analysis to classified sites into 3 major groups based on Chironomidae assemblages. These groups were explained mainly by longitudinal zonation and geographical position, and were defined as 1) siliceous headwater streams, 2) mid-altitude streams with small catchment areas, and 3) medium-sized calcareous streams. Distinct species assemblages with associated indicator taxa were established for each stream category using IndVal analysis. Species responses to previously identified key environmental variables were determined, and optima and tolerances were established by weighted average regression. Distinct ecological requirements were observed among genera and among species of the same genus. Some genera were restricted to headwater systems (e.g., Diamesa), whereas others (e.g., Eukiefferiella) had wider ecological preferences but with distinct distributions among congenerics. In the present period of climate change, optima and tolerances of species might be a useful tool to predict responses of different species to changes in significant environmental variables, such as temperature and hydrology.
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Especially in global enterprises, key data is fragmented in multiple Enterprise Resource Planning (ERP) systems. Thus the data is inconsistent, fragmented and redundant across the various systems. Master Data Management (MDM) is a concept, which creates cross-references between customers, suppliers and business units, and enables corporate hierarchies and structures. The overall goal for MDM is the ability to create an enterprise-wide consistent data model, which enables analyzing and reporting customer and supplier data. The goal of the study was defining the properties and success factors of a master data system. The theoretical background was based on literature and the case consisted of enterprise specific needs and demands. The theoretical part presents the concept, background, and principles of MDM and then the phases of system planning and implementation project. Case consists of background, definition of as is situation, definition of project, evaluation criterions and concludes the key results of the thesis. In the end chapter Conclusions combines common principles with the results of the case. The case part ended up dividing important factors of the system in success factors, technical requirements and business benefits. To clarify the project and find funding for the project, business benefits have to be defined and the realization has to be monitored. The thesis found out six success factors for the MDM system: Well defined business case, data management and monitoring, data models and structures defined and maintained, customer and supplier data governance, delivery and quality, commitment, and continuous communication with business. Technical requirements emerged several times during the thesis and therefore those can’t be ignored in the project. Conclusions chapter goes through these factors on a general level. The success factors and technical requirements are related to the essentials of MDM: Governance, Action and Quality. This chapter could be used as guidance in a master data management project.
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The physical education curriculum stresses the importance of improving students’ key motor skills. This idea agrees with the contributions of research into motor development concerning the important role these skills play in child development. In order to facilitate this improvement is essential to know the different basic aspects of how these key motor skills evolve as well as the essential factors related to the characteristics and conditions of educational practice
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The ability of the supplier firm to generate and utilise customer-specific knowledge has attracted increasing attention in the academic literature during the last decade. It has been argued the customer knowledge should treated as a strategic asset the same as any other intangible assets. Yet, at the same time it has been shown that the management of customer-specific knowledge is challenging in practice, and that many firms are better at acquiring customer knowledge than at making use of it. This study examines customer knowledge processing in the context of key account management in large industrial firms. This focus was chosen because key accounts are demanding and complex. It is not unusual for a single key account relationship to constitute a complex web of relationships between the supplier and the key account – thus easily leading to the dispersion of customer-specific knowledge in the supplier firm. Although the importance of customer-specific knowledge generation has been widely acknowledged in the literature, surprisingly little attention has been paid to the processes through which firms generate, disseminate and use such knowledge internally for enhancing the relationships with their major, strategically important key account customers. This thesis consists of two parts. The first part comprises a theoretical overview and draws together the main findings of the study, whereas the second part consists of five complementary empirical research papers based on survey data gathered from large industrial firms in Finland. The findings suggest that the management of customer knowledge generated about and form key accounts is a three-dimensional process consisting of acquisition, dissemination and utilization. It could be concluded from the results that customer-specific knowledge is a strategic asset because the supplier’s customer knowledge processing activities have a positive effect on supplier’s key account performance. Moreover, in examining the determinants of each phase separately the study identifies a number of intra-organisational factors that facilitate the process in supplier firms. The main contribution of the thesis lies in linking the concept of customer knowledge processing to the previous literature on key account management. Moreover, given than this literature is mainly conceptual or case-based, a further contribution is to examine its consequences and determinants based on quantitative empirical data.
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Cleaner technologies include products, services, technologies, processes and systems that in use create less environmental hazard than the existing alternatives. Rapidly growing cleantech sector possesses an essential competitive advantage in the future. However, no profound research has been conducted on the characteristics of cleaner technologies and their effect on the commercialization process. This thesis aims at synthesizing scattered information and creating a basis for accelerating cleaner technology commercialization in Finnish context. Two research questions are defined: 1. What are the key challenges and success factors in the commercialization of cleaner technologies based on the existing literature? 2. What kind of lessons can be learned from the Finnish success stories of cleantech commercialization? The research was conducted as a literature review and supported with three case interviews. The results suggest that literature-based challenges are mostly related to, for example, difficulty in gathering customer information, unrealistic customer expectations, lack of resources, networks and proper success indicators, legislation, and unstructured strategy planning stemming from company culture. Handling the barriers require, above all, open communication from all stakeholders, management commitment and accurate goal setting, government-driven funding and incentives, and cooperation with educational facilities. Finnish success cases emphasize especially customer attention: listening to customers and receiving feedback from them during the whole commercialization process to correct the errors early and save resources, visionary in fulfilling customer needs, ability to question company’s own business performance, not being afraid of making mistakes but learning from them, and continuously observing and evaluating the commercialization process.
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The purpose of this study is to identify factors contributory to success or failure of a microenterprise. Microenterprise is an enterprise with less than10 employees. About 99 % of all Finnish enterprises fall in this category. Earlier studies do not provide a comprehensive view on microenterprise success and failure factors. The theoretical part discusses the definition of success and failure, previous research and results already established about the topic and categories of business environment. The empirical part is founded on quantitative survey results from 204 Finnish microenterprises. The questions of the survey were based on previous surveys, literature and intuition. Both success and failure factors were enquired. Summary of the results was made and the results were compared among successful and unsuccessful enterprises. In open-end questions, the most important factors mentioned to affect enterprise performance positively were "Employees", "Customers" and "Skills, knowledge, education and experience." The most important factors affecting enterprise performance negatively were "Economical situation", "Employees availability and attitudes" as well as "Political decisions and passed laws". In Likert-scale set of questions, the most significant factors from the point of view of enterprise performance were "Product and / or service good quality", "Good reputation of the company" and "Staff's strong skills". The least significant factors were "Effect of marketing and promotion", "Conflicts" and "Differences of points of views of different generations". By Likert-scale set of questions, it was also tested which operations the enterprises perform, and according to the results, successful enterprises found "Performing a market research", "Use of distribution channel in sales" and "Expanding to new markets" less important than unsuccessful enterprises. The tests proved that the age of the enterprise correlates with the level of success of the enterprise: The younger the enterprise, the more successful it is. In addition, the results show that if the enterprise is family based, the less successful it is. In addition, there was also slight correlation between success and the level of growth, indicating that higher the level of growth the more successful the enterprise is. From the business environment point of view, the key finding was that internal factors affect more on the success of an enterprise than external factors, and that external factors affect more on the failure of an enterprise than internal factors.
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Disorders of male reproductive health are becoming increasingly prevalent globally. These defects, ranging from decreasing sperm counts to an increasing rate of infertility and testicular cancer, have a common origin in the early phases of testicular development, but the exact mechanisms that cause them remain unknown. Testicular development and adult spermatogenesis are complex processes in which different cell types undergo mitosis, meiosis, differentiation and apoptosis. The retinoblastoma protein family and its associated E2F transcription factors are key regulators of these cellular events. In the present study, the functions of these factors in postnatal testicular development and adult spermatogenesis were explored using different animal models. In addition, a new application of flow cytometry to study testicular cell dynamics was developed. An ablation of retinoblastoma protein in mouse Sertoli cells resulted in their cell cycle re-entry in adult testes, dedifferentiation and a severe spermatogenic defect. We showed that deregulated E2F3 contributed to these changes. Our results indicated that the E2F1 transcription factor is critical for the control of apoptosis in the developing postnatal testis. In the adult testis, E2F1 controls the maintenance of the spermatogonial stem cell pool, in addition to inhibiting apoptosis of spermatocytes. In summary, this study elucidated the complex interdependencies of the RB and E2F transcription factor families in the control of postnatal testicular development and adult spermatogenesis. Furthermore, this study provided a new methodology for the analysis of testicular cells.
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Municipalities that engage in recreation planning have the potential to use their resources more effectively. However, successful planning means getting the plan off the shelf and implemented. This study investigated the factors that influenced municipal recreation plan implementation in three municipalities. Interviews were conducted with eleven key informants (recreation directors, planning consultants, a city councillor, and members of plan steering committees). The findings of this study suggested that because the implementation of recreation plans occurs in a highly political environment, recreation professionals will need effective strategies to get their plans implemented and that implementation can be facilitated by developing or expanding strategies that: (l) build the power of the recreation department within the municipal government structure; (2) build support for recreation within the local community; and (3) build the political and organizational capacity in the recreation department.
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Within the context of international adoption, previous research has focused on parentchild attachment relationships and various aspects of the adoption process. However, less is known about other aspects of parent-child relationships (e.g., cohesion, conflict) within internationally adoptive families. Additionally, there is a need for research that explores both parent and child perceptions of the process of adoption - including pre- and post-adoptive factors - and its connection to the quality of parent-child relationships. This research utilized a qualitatively-oriented methodology to conduct separate, in-depth interviews with 10 adoptive Canadian mothers and their adopted Chinese children (aged 9 to 11 years). Results highlight parent and child reports of mainly strong, positive relationships. Several pre-adoption experiences are examined, including institutionalization, age at the time of adoption, and parental stress/expectations. A key finding concerns the link that adoptive parents perceive between the quality of their child's pre-adoptive care (i.e., mainly early institutionalized care) and the quality of their relationship. Interestingly, this link is perceived in two different ways - either as a challenge for the parent-child relationship or as a means to strengthen it. Post-adoption experiences are also explored, including cultural socialization, creating a transracial family, discussing adoption, parental stress, and sibling involvement. A key finding involves parent and child reports that cultural socialization efforts (i.e., familiarizing children with Chinese culture) are linked to more positive parent-child relationships. The implications of these findings are discussed in relation to theory and practice within the context of international adoption.
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Postsecondary enrolments of young males has been declining since the mid-1980s. The decline can be attributed, at least in part, to boys and young men being unable to compete for a fixed number of available places in institutions of higher learning, whether in community college or university. This inability to compete stems from their academic performance in secondary school. This study interviewed adolescent males and their parents as to their perceptions of a number of factors that may contribute to their academic performance. Those factors included noncognitive skills, dimensions of character, perceptions of teachers, general attitudes towards school, and likes and dislikes on a range of course subjects. One of the most important findings was that only one of the seven adolescent male participants was considering a future career that would require a university degree. Other findings showed the young men's noncognitive skills were weak, particularly in relation to time management skills and their unwillingness to ask for help with schoolwork and homework. Most of the young men expressed a dislike for mathematics beyond high school, a subject key to the study, of the natural sciences, engineering, technology, and business. Recommendations include school reforms both inside the classroom and beyond. Additionally, a framework using project management theory and practice has been proposed to improve noncognitive skills, dimensions of character, and executive function.
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La documentation scientifique fait état de la présence, chez l’adulte, de cellules souches et progénitrices neurales (CSPN) endogènes dans les zones sous-ventriculaire et sous-granulaire du cerveau ainsi que dans le gyrus denté de l’hippocampe. De plus, un postulat selon lequel il serait également possible de retrouver ce type de cellules dans la moelle épinière et le néocortex des mammifères adultes a été énoncé. L’encéphalopathie de Wernicke, un trouble neurologique grave toutefois réversible qui entraîne un dysfonctionnement, voire une défaillance du cerveau, est causée principalement par une carence importante en thiamine (CT). Des observations récentes laissent envisager que les facteurs en cause dans la prolifération et la différenciation des CSPN pourraient également jouer un rôle important lors d’un épisode de CT. L’hypothèse, selon laquelle l’identification de nouveaux métabolites entrant dans le mécanisme ou la séquence de réactions se soldant en une CT pourraient en faciliter la compréhension, a été émise au moyen d'une démarche en cours permettant d’établir le profil des modifications métaboliques qui surviennent en de telles situations. Cette approche a été utilisée pour constater les changements métaboliques survenus au niveau du foyer cérébral dans un modèle de rats déficients en thiamine (rats DT), particulièrement au niveau du thalamus et du colliculus inférieur (CI). La greffe de CSPN a quant à elle été envisagée afin d’apporter de nouvelles informations sur la participation des CSPN lors d’un épisode de CT et de déterminer les bénéfices thérapeutiques potentiels offerts par cette intervention. Les sujets de l’étude étaient répartis en quatre groupes expérimentaux : un premier groupe constitué de rats dont la CT était induite par la pyrithiamine (rats DTiP), un deuxième groupe constitué de rats-contrôles nourris ensemble (« pair-fed control rats » ou rats PFC) ainsi que deux groupes de rats ayant subi une greffe de CSPN, soit un groupe de rats DTiP greffés et un dernier groupe constitué de rats-contrôles (rats PFC) greffés. Les échantillons de foyers cérébraux (thalamus et CI) des quatre groupes de rats ont été prélevés et soumis à des analyses métabolomiques non ciblées ainsi qu’à une analyse visuelle par microscopie à balayage électronique (SEM). Une variété de métabolites-clés a été observée chez les groupes de rats déficients en thiamine (rats DTiP) en plus de plusieurs métabolites dont la documentation ne faisait pas mention. On a notamment constaté la présence d’acides biliaires, d’acide cynurénique et d’acide 1,9— diméthylurique dans le thalamus, alors que la présence de taurine et de carnosine a été observée dans le colliculus inférieur. L’étude a de plus démontré une possible implication des CSPN endogènes dans les foyers cérébraux du thalamus et du colliculus inférieur en identifiant les métabolites-clés ciblant les CSPN. Enfin, les analyses par SEM ont montré une amélioration notable des tissus à la suite de la greffe de CSPN. Ces constatations suggèrent que l’utilisation de CSPN pourrait s’avérer une avenue thérapeutique intéressante pour soulager la dégénérescence symptomatique liée à une grave carence en thiamine chez l’humain.