Tuotannollisen testerin suunnittelu tiedonsiirtolinkkikortille

Työssä suunniteltiin ja toteutettiin linkkikorttien tuotannollinen testeri. Linkkikortti on osa CERN:iin rakennettavan hiukkaskiihdyttimen Large Hadron Colliderin koeasema Compact Muon Solenoidin luentajärjestelmää. Linkkikortin tehtävänä on muuttaa rinnakkaismuotoinen LVDS-signaali sarjamuotoiseksi optiseksi signaaliksi. Testattaessa testeri ja linkkikortti sijoitetaan kehikkoon, joten testerin liittimien pitää olla linkkikortin liittimien kanssa identtisiä. Testerin lähdöt ovat linkkikortin tuloja ja toisinpäin. Tällöin testattaessa voidaan ohjelmoitavien FPGA-piirien avulla lähettää signaalia kortilta toiselle. Vastaanottavan kortin FPGA-piirin avulla voidaan tarkistaa, onko data tullut perille muuttumattomana. Testin ohjaus tapahtuu tietokoneella, jolla käyttäjä antaa käskyn testin aloittamisesta ja jonne lopulta myös raportoidaan testin tulokset. Testien tulokset näytetään myös testerin ledeillä. Työssä ei pystytä linkkikorttien puuttumisen takia testaamaan testeriä loppukäytössään. Kuitenkin testerin toimivuus pystyttiin suurilta osin testaamaan, jolloin saatiin odotettuja tuloksia.

Family Alliance as a Moderator of the Link Between Maternal Postpartum Depression and Child Symptoms Assessed by Both Parents

We investigated the moderating effect of family relationships on the links between maternal postpartum depression and child symptoms in a low-risk community sample of families with 3-month-old infants (n = 57). The level of maternal depression was assessed by the Montgomery-Asberg Depression Rating Scale from a clinical interview, child symptoms by the Symptom Check List completed by both parents, and family relationships by direct observation of father-mother-baby interactions (Lausanne Trilogue Play). Families were categorized as high coordination or low coordination from their overall coordination level throughout the play. Results showed no significant links between maternal depression level and child symptoms reported by both parents. Mothers with a high depressive level in high coordination families tended to report more symptoms in their child than did mothers with lower depressive scores, whereas this link was not found in low coordination families. Prevention perspectives and clinical implications of these results are discussed.

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

Defective nitric oxide synthesis: a link between metabolic insulin resistance, sympathetic overactivity and cardiovascular morbidity.

Epidemiological studies demonstrate an association between insulin resistance, hypertension and cardiovascular morbidity. In addition to its metabolic effects, insulin also has important cardiovascular actions. The sympathetic nervous system and the nitric oxide-l-arginine pathway have emerged as central players in the mediation of these actions. Over the past decade, the underlying mechanisms and the factors that may govern the interaction between insulin and these two major cardiovascular regulatory systems have been studied extensively in healthy people and insulin-resistant individuals. Here we summarize the current understanding and gaps in knowledge on these interactions. We propose that a genetic and/or acquired defect of nitric oxide synthesis could represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant states, all of which may predispose to cardiovascular disease.

Neurobiology of addiction: the role of transcription factors CREB and C/EBP as well as that of their coactivators

Résumé Le présent travail de thèse a fait face au défi de lier les changements transcriptionnels dans les neurones du système nerveux central au développement de l'addiction aux drogues. I1 est connu que l'apprentissage induit des modifications au niveau de la structure du cerveau, principalement en changeant la manière dont les neurones sont interconnectés par des synapses. De plus en plus d'évidences soutiennent un scénario selon lequel l'activité neuronale déclenche des cascades de signalisation intracellulaire qui ciblent des facteurs de transcription. Ces derniers peuvent activer la transcription de gènes spécifiques qui codent pour des protéines nécessaires au renforcement des synapses mémorisant ainsi la nouvelle information. Puisque l'addiction peut être considérée comme une forme aberrante d'apprentissage, et que les modifications synaptiques sont connues pour être impliquées dans le processus d'addiction, nous essayons de décrire des mécanismes transcriptionels étant à la base des changements synaptiques induits par les drogues. Comme modèle nous utilisons des cultures primaires des neurones de striatum, d'hippocampe et de cortex de souris ainsi que des tranches de cerveau de rat. Une des caractéristiques communes de quasiment toutes les substances addictives est de pouvoir activer le système mésolimbique dopaminergique provoquant la libération de dopamine sur les neurones du striatum (du noyau accumbens). Dans ce travail de thèse nous démontrons que dans des cultures du striatum, la dopamine induit le facteur de transcription C/EBPβ qui, à son tour, provoque l'expression du gène codant pour la substance P. Ce mécanisme pourrait potentiellement contribuer à la tolérance envers les drogues puisqu'il fait partie d'une rétroaction (feed-back) sur les cellules produisant la dopamine. Etant donné que ces résultats montrent l'importance de C/EBPβ dans la psychopathologie de l'addiction, nous avons également décidé d'étudier les mécanismes fondamentaux de l'activation de la transcription par C/EBPβ. Nos expériences démontrent que trois isoformes activatrices de la famille C/EBP recrutent le coactivateur CBP et provoquent en même temps sa phosphorylation. Enfin, nous montrons que les coactivateurs nommés TORC, nouvellement découverts et clonés, sont capables de détecter la coïncidence d'un signal cAMP et d'une entrée de calcium dans des neurones. Par conséquent les TORCs pourraient contribuer à détecter la coïncidence d'un signal glutamate et d'un signal dopamine dans les neurones de striatum, ce qui pourrait être important pour associer les effets hédonistes de la drogue à l'information contextuelle (par exemple à l'environnement où la drogue a été consommée). Nous sommes les premiers à observer que les TORCs sont nécessaires pour la potentiation à long terme dans l'hippocampe. Summary The present thesis work faced the challenge to link the development of drug addiction to transcriptional changes in the neurons of the central nervous system. Experience and learning are known to induce structural modifications in the brain, and these changes are thought to occur mainly in the way neurons are interconnected by synapses. More and more evidences point to a scenario in which neuronal activity would activate signalization cascades that impinge on transcription factors, which, in turn, would activate genes necessary for the reinforcement of synapses coding for new informations. Given that drug addiction can be considered as an aberrant form of learning and is thought to involve synaptic modifications, we try to elucidate some of the transcriptional mechanisms that could underlie drug-induced synaptic changes. As a model system, we use primary cultures of striatal, cortical and hippocampal neurons dissected from mouse embryos as well as brain slices from rats. One of the common features of virtually all drugs of abuse is to activate the mesocorticolimbic dopaminergic system that results in the release of dopamine onto the neurons of the striatum (nucleus accumbens). In this thesis work we show that in striatal cultures, dopamine induces the transcription factor C/EBPβ that in turn drives the expression of the gene coding for substance P. This mechanism is likely to be important for the drug-induced tolerance in the brain since it might be a part of a feedback acting on dopaminergic neurons. Given the suspected importance of C/EBPβ in drug addiction, we also try to elucidate some aspects of the basic mechanisms by which the C/EBP family activates transcription. We show that three activating members of the C/EBP family recruit the coactivator CBP and trigger its phosphorylation. Finally, we demonstrate that the newly discovered and cloned transcriptional coactivators, named TORCs (transducers of regulated CREB activity) are able to detect the coincidence of a calcium and a cAMP signal in the central nervous system. This way, TORCs could contribute to the detection of a coincidence between a glutamate and a dopamine signal in striatal neurons - a process that is suggested to be important for an association between the rewarding effect of a drug and contextual information (such as the environment where the drug had been taken). We demonstrate that TORCs are required for hippocampal LTP.

In Search of Corporate Renewal: How to Benefit from Corporate Venturing?

Despite the rapid change in today's business environment there are relatively few studies about corporate renewal. This study aims for its part at filling that research gap by studying the concepts of strategy, corporate renewal, innovation and corporate venturing. Its purpose is to enhance our understanding of how established companies operating in dynamic and global environment can benefit from their corporate venturing activities. The theoretical part approaches the research problem in corporate and venture levels. Firstly, it focuses on mapping the determinants of strategy and suggests using industry, location, resources, knowledge, structure and culture, market, technology and business model to assess the environment and using these determinants to optimize speed and magnitude of change.Secondly, it concludes that the choice of innovation strategy is dependent on the type and dimensions of innovation and suggests assessing market, technology, business model as well as novelty and complexity related to each of them for choosing an optimal context for developing innovations further. Thirdly, it directsattention on processes through which corporate renewal takes place. On corporate level these processes are identified as strategy formulation, strategy formation and strategy implementation. On the venture level the renewal processes are identified as learning, leveraging and nesting. The theoretical contribution of this study, the framework of strategic corporate venturing, joins corporate and venture level management issues together and concludes that strategy processes and linking processes are the mechanism through which continuous corporate renewaltakes place. The framework of strategic corporate venturing proposed by this study is a new way to illustrate the role of corporate venturing as a purposefullybuilt, different view of a company's business environment. The empirical part extended the framework by enhancing our understanding of the link between corporate renewal and corporate venturing in its real life environment in three Finnish companies: Metso, Nokia and TeliaSonera. Characterizing companies' environmentwith the determinants of strategy identified in this study provided a structured way to analyze their competitive position and renewal challenges that they arefacing. More importantly the case studies confirmed that a link between corporate renewal and corporate venturing exists and found out that the link is not as straight forward as indicated by the theory. Furthermore, the case studies enhanced the framework by indicating a sequence according to which the processes work. Firstly, the induced strategy processes strategy formulation and strategy implementation set the scene for corporate venturing context and management processes and leave strategy formation for the venture. Only after that can strategies formed by ventures come back to the corporate level - and if found viable in the corporate level be formalized through formulation and implementation. With the help of the framework of strategic corporate venturing the link between corporaterenewal and corporate venturing can be found and managed. The suggested response to the continuous need for change is continuous renewal i.e. institutionalizing corporate renewal in the strategy processes of the company. As far as benefiting from venturing is concerned the answer lies in deliberately managing venturing in a context different to the mainstream businesses and establishing efficientlinking processes to exploit the renewal potential of individual ventures.

Data-parallel computation in parallel and distributed environments

The past few decades have seen a considerable increase in the number of parallel and distributed systems. With the development of more complex applications, the need for more powerful systems has emerged and various parallel and distributed environments have been designed and implemented. Each of the environments, including hardware and software, has unique strengths and weaknesses. There is no single parallel environment that can be identified as the best environment for all applications with respect to hardware and software properties. The main goal of this thesis is to provide a novel way of performing data-parallel computation in parallel and distributed environments by utilizing the best characteristics of difference aspects of parallel computing. For the purpose of this thesis, three aspects of parallel computing were identified and studied. First, three parallel environments (shared memory, distributed memory, and a network of workstations) are evaluated to quantify theirsuitability for different parallel applications. Due to the parallel and distributed nature of the environments, networks connecting the processors in these environments were investigated with respect to their performance characteristics. Second, scheduling algorithms are studied in order to make them more efficient and effective. A concept of application-specific information scheduling is introduced. The application- specific information is data about the workload extractedfrom an application, which is provided to a scheduling algorithm. Three scheduling algorithms are enhanced to utilize the application-specific information to further refine their scheduling properties. A more accurate description of the workload is especially important in cases where the workunits are heterogeneous and the parallel environment is heterogeneous and/or non-dedicated. The results obtained show that the additional information regarding the workload has a positive impact on the performance of applications. Third, a programming paradigm for networks of symmetric multiprocessor (SMP) workstations is introduced. The MPIT programming paradigm incorporates the Message Passing Interface (MPI) with threads to provide a methodology to write parallel applications that efficiently utilize the available resources and minimize the overhead. The MPIT allows for communication and computation to overlap by deploying a dedicated thread for communication. Furthermore, the programming paradigm implements an application-specific scheduling algorithm. The scheduling algorithm is executed by the communication thread. Thus, the scheduling does not affect the execution of the parallel application. Performance results achieved from the MPIT show that considerable improvements over conventional MPI applications are achieved.

Introducing massively parallel computers into operational weather forecasting

Numerical weather prediction and climate simulation have been among the computationally most demanding applications of high performance computing eversince they were started in the 1950's. Since the 1980's, the most powerful computers have featured an ever larger number of processors. By the early 2000's, this number is often several thousand. An operational weather model must use all these processors in a highly coordinated fashion. The critical resource in running such models is not computation, but the amount of necessary communication between the processors. The communication capacity of parallel computers often fallsfar short of their computational power. The articles in this thesis cover fourteen years of research into how to harness thousands of processors on a single weather forecast or climate simulation, so that the application can benefit as much as possible from the power of parallel high performance computers. The resultsattained in these articles have already been widely applied, so that currently most of the organizations that carry out global weather forecasting or climate simulation anywhere in the world use methods introduced in them. Some further studies extend parallelization opportunities into other parts of the weather forecasting environment, in particular to data assimilation of satellite observations.