L’endothéline-1 (ET-1) est un peptide vasoactif extrêmement puissant qui possède une forte activité mitogénique dans les cellules du muscle lisse vasculaire (VSMCs). Il a été démontré que l’ET-1 est impliquée dans plusieurs maladies cardio-vasculaires, comme l’athérosclérose, l'hypertension, la resténose après l'angioplastie, l’insuffisance cardiaque et l'arythmie. L’ET-1 exerce ses effets via plusieurs voies de signalisation qui incluent le Ca2+, les protéines kinases activées par les mitogènes (MAPKs) y compris les kinases régulées par les signaux extracellulaires (ERK1/2) et la voie de la phosphatidylinositol 3-kinase (PI-3K)/protein kinase B (PKB). Plusieurs études ont démontré que les dérivés réactifs de l'oxygène (ROS) peuvent jouer un rôle important dans la signalisation d’ERK1/2 et de PKB induite par plusieurs facteurs de croissance et hormones. Nous avons précédemment montré que l'ET-1 produit des ROS qui agissent comme médiateur de la signalisation cellulaire induite par l’ET-1. Le peroxyde d’hydrogène (H2O2), une molécule qui appartient à la famille des ROS, peut activer les voies de la MAPK et de la PKB dans les VSMCs. Par ailleurs, nos résultats suggèrent également que le Ca2+ et la calmoduline (CaM) sont essentiels pour la phosphorylation d’ERK1/2, de p38 et de PKB induite par le H2O2 dans les VSMCs. La Ca2+/CaM-dependent protein kinases II (CaMKII) est une sérine/thréonine protéine kinase multifonctionnelle activée par le Ca2+/CaM. Il a été montré que la CaMKII est impliquée dans les voies de signalisation induite par le H2O2 dans les cellules endothéliales. Cependant, le rôle de la CaMKII dans la phosphorylation d’ERK1/2, de PKB et de la proline-rich tyrosine kinase 2 (Pyk2) induite par l’ET-1 et le H2O2, de même que son rôle dans l’effet hypertrophique et prolifératif de l’ET-1 dans les VSMCs demeure inexploré. Le monoxyde d’azote (NO) est une molécule vasoactive impliquée dans la régulation de plusieurs réponses hormonales. Le NO peut moduler la signalisation contrôlant la croissance cellulaire induite par plusieurs agonistes d’où son rôle protecteur dans le système vasculaire. Des études ont montré que le NO peut inhiber la voie de Ras/Raf/ERK1/2 et la voie de PKB induite par le facteur de croissance endothélial (EGF) et l’angiotensine II (Ang II). Beaucoup d’autres travaux ont mis en évidence un cross-talk entre les voies de signalisation activées par l’ET-1 et le NO. La capacité du NO à inhiber la signalisation intracellulaire induite par l’ET-1 dans les VSMCs demeure inconnue. Le travail présenté dans cette thèse vise à déterminer le rôle du système Ca2+-CaM-CaMKII dans la phosphorylation d’ERK1/2, de PKB et de Pyk2 induite par l’ET-1 et le H2O2 ainsi que son rôle dans la croissance et la prolifération cellulaire induites par l’ET-1 dans les VSMCs. Nous avons également testé le rôle du NO dans la phosphorylation d’ERK1/2, de PKB et de Pyk2 ainsi que la synthèse protéique induite par l’ET-1. Dans la première partie de notre étude, nous avons examiné le rôle de la CaMKII dans la phosphorylation d’ERK1/2 et de PKB induite par l’ET-1 dans les VSMCs en utilisant trois approches différentes i.e. l'usage d'inhibiteurs pharmacologiques, un peptide auto-inhibiteur de la CaMKII (CaMKII AIP) et la technique de siRNA. Nous avons démontré que la CaMKII est impliquée dans la phosphorylation d’ERK1/2 et de PKB induite par l’ET-1 dans les VSMCs. Des études précédentes ont montré à l’aide d’inhibiteurs pharmacologiques comme le KN-93 que l'Ang II et les agents induisant une augmentation de la concentration en Ca2+ intracellulaire comme l’ionomycine, provoquent la phosphorylation d’ERK1/2 via la CaM dans les VSMCs. Cependant, en utilisant différentes approches, nos études ont montré pour la première fois une implication de la CaMKII dans la phosphorylation d’ERK1/2 et de PKB induite par l’ET-1 dans les VSMCs. Nous avons également rapporté pour la première fois, un rôle crucial de la CaMKII dans la pathophysiologie vasculaire associée à l’ET-1 puisque l’activation de la CaMKII joue un rôle important dans l’hypertrophie et la croissance cellulaire. Dans la deuxième partie, à la lumière des études précédentes qui montraient que les ROS agissent comme médiateurs de la signalisation induite par l’ET-1 dans les VSMCs, nous avons examiné si la CaMKII est également impliquée dans l’activation des voies d’ERK1/2 et de PKB induite par le H2O2. En utilisant des approches pharmacologiques et moléculaires, nous avons montré, comme pour l’ET-1, que la CaMKII joue un rôle critique en amont de la phosphorylation d’ERK1/2, de PKB et de Pyk2 induite par le H2O2. Nous avons précédemment montré que la transactivation du récepteur de type I de l’insulin-like growth factor (IGF-1R) est nécessaire à l’activation de PKB induite par le H2O2. Pour cette raison, nous avons examiné l'effet de l'inhibition de la CaMKII par l’inhibiteur pharmacologique ou par le knock-down de la CaMKII sur la phosphorylation d’IGF-1R induite par le H2O2. Les résultats démontrent que la CaMKII joue un rôle critique en amont de la phosphorylation d’ERK1/2, de PKB et d’IGF-1R induite par le H2O2. Dans la troisième partie de notre étude, nous avons également examiné le mécanisme moléculaire par lequel le NO exerce ses effets anti-mitogéniques et anti-hypertrophiques dans la signalisation induite par l’ET-1. En testant l'effet de deux différents donneurs de NO (S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (SNP)) et un inhibiteur de NO synthase, le N (G)-nitro-L-arginine methyl ester (L-NAME) dans la phosphorylation d’ERK1/2, de PKB et de Pyk2 induite par l’ET-1, nous avons observé que le NO a un effet inhibiteur sur la signalisation induite par l’ET-1 dans les VSMCs. Par ailleurs, le 8-Br-GMPc, un analogue du GMPc, a un effet similaire à celui des deux donneurs du NO, tandis que l’oxadiazole quinoxaline (ODQ), un inhibiteur de la guanylate cyclase soluble, inverse l'effet inhibiteur du NO. Nous concluons que le NO diminue la phosphorylation d’ERK1/2, de PKB et de Pyk2 induite par l’ET-1 d’une manière dépendante du GMPc. Le NO inhibe aussi les effets hypertrophiques de l’ET-1 puisque le traitement avec le SNAP diminue la synthèse des protéines induite par l’ET-1. En résumé, les études présentées dans cette thèse démontrent que l’ET-1 et le H2O2 sont des activateurs de la phosphorylation d’ERK1/2, de PKB et de Pyk2 dans les VSMCs et que la CaMKII s’avère nécessaire pour ce processus, en agissant en amont de l’activation de IGF-1R induite par le H2O2 dans les VSMCs. Elles montrent également que le NO inhibe la phosphorylation d’ERK1/2, de PKB et de Pyk2 induite par l’ET-1. Enfin, nos travaux suggèrent aussi que l’activation de la CaMKII stimule la synthèse des protéines et de l’ADN induites par l’ET-1 alors que le NO inhibe la synthèse des protéines induite par ET-1. Mots clés: Endothéline ; Peroxyde d'hydrogène ; CaMKII ; Monoxyde d’azote ; Système vasculaire ; PKB; ERK1/2; IGF-1R; Hypertrophie. / Endothelin-1 has emerged as an extremely potent vasoactive peptide exhibiting potent mitogenic activity in vascular smooth muscle cells (VSMCs). A critical role of ET-1 in many cardiovascular diseases, such as atherosclerosis, hypertension, restenosis after angioplasty, heart failure and arrhythmia has been suggested. ET-1 exerts its effects through multiple signaling pathways which include Ca2+, mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI-3K)/protein kinase B (PKB)/Akt pathways. Several studies have also demonstrated that reactive oxygen species (ROS) may play an important role in mediating the signals of several growth factors and peptides hormones linked to these pathways. We have previously reported that ET-1 generates ROS which mediates ET-1-induced signaling. H2O2, an important ROS molecule, activates both MAPKs and PKB signaling in VSMCs. In addition, we have also suggested that Ca2+ and CaM are essential to trigger H2O2-induced ERK1/2, p38 and PKB phosphorylation in A-10 VSMCs. Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine protein kinase which is believed to transduce the downstream effects of Ca2+/CaM, and has been shown to be involved in H2O2-induced signaling in endothelial cells. However, a role of CaMKII in mediating ET-1 and H2O2-induced ERK1/2, PKB, Pyk2 phosphorylation, as well as its effect on hypertrophic and proliferative responses of ET-1 in VSMCs remains unexplored. Interestingly, a role of CaMKII in several cardiovascular diseases has been reported and studies showing that pharmacological inhibition of CaMKII, by using KN-93, prevent arrhythmic activity improved vascular dysfunction in diabetes or in Ang II-induced hypertension. Nitric oxide (NO) is also an important reactive species and vasoactive molecule involved in the regulation of several hormone-mediated responses. NO has been suggested to modify growth-promoting signaling events and thus may serve as a vascular protective agent. Studies have shown that NO can attenuate EGF and Ang II-induced Ras/Raf/ERK1/2 as well as increase in PKB phosphorylation signaling pathways. There is also evidence for a potential cross-talk between ET-1 and NO, however not much information on the ability of NO to modify ET-1-induced signaling in VSMCs is available. Therefore, the work presented in this thesis has investigated the role of CaMKII system in ET-1 and H2O2-induced ERK1/2, PKB and Pyk2 phosphorylation, as well as in cell growth and proliferation evoked by ET-1 in VSMCs. We also investigated the role of NO in ET-1-induced ERK1/2, PKB and Pyk2 phosphorylation as well as protein synthesis. In the first part of our studies, by using three different approaches, i.e. use of pharmacological inhibitors, a CaMKII AIP (autoinhibitor peptide) and siRNA techniques, we have investigated the involvement of CaMKII in ET-1-induced ERK1/2 and PKB phosphorylation in A-10 VSMC. We have demonstrated that CaMKII mediates the effect of ET-1 on ERK1/2 and PKB phosphorylation in A-10 VSMC. By using pharmacological inhibitor alone such as, KN-93, earlier studies have reported that AngII and Ca2+ elevating agents, such as ionomycin, exert their effects on ERK1/2 phosphorylation via CaM-dependent pathways in VSMC. However, by using multiple approaches, our studies, have provided the first evidence to suggest an involvement of CaMKII in mediating the effect of ET-1 on ERK1/2 and PKB phosphorylation in A-10 VSMC. We have also reported for the first time, a crucial role of CaMKII in vascular pathophysiology related to ET-1 by regulating the growth and hypertrophic events by using the technique of [3H]leucine and [3H]thymidine incorporation. In the second part, in view of earlier studies showing that ROS mediates ET-1-induced signaling events in VSMC, we have also investigated if CaMKII is also implicated in H2O2-induced activation of ERK1/2 and PKB pathways. By using both pharmacological and molecular approaches, we show that similar to ET-1, CaMKII serves as a critical upstream component in triggering H2O2-induced ERK1/2, PKB and Pyk2 phosphorylation in VSMC. Furthermore, since we have previously reported that IGF-1R transactivation is needed for H2O2-induced PKB activation, we have investigated the effect of CaMKII inhibition and knocking-down on IGF-1R phosphorylation evoked by H2O2. Taken together, these results demonstrate that CaMKII plays a critical upstream role in mediating the effect of H2O2 on ERK1/2, PKB and IGF-1R phosphorylation. In the third part of our studies, we have investigated the molecular mechanism by which NO exerts its anti-mitogenic and anti-hypertrophic effect on ET-1-induced signaling. By testing the effect of two different NO donors (SNAP and SNP) and L-NAME, an inhibitor of NO synthase, in ET-1-induced ERK1/2, PKB and Pyk2 phosphorylation, we observed that NO has an inhibitory effect in ET-1-induced signaling in VSMC. In addition, 8-Br-cGMP, an analogue of cGMP, exerted similar effect to that of NO donors whereas, oxadiazole quinoxalin (ODQ), an inhibitor of soluble guanylyl cyclase (sGC), reversed the inhibitory effect of NO. We conclude that NO, in a cGMP-dependent manner, attenuated ET-1-induced phosphorylation of ERK1/2, PKB and Pyk2 and also antagonized the hypertrophic effects of ET-1, since SNAP treatment decreased the protein synthesis induced by ET-1. In summary, the studies presented in this thesis demonstrate that both ET-1 and H2O2 induce ERK1/2, PKB and Pyk2 phosphorylation in VSMC and CaMKII activation is required for these events. We have also shown that CaMKII phosphorylation is upstream of H2O2-induced IGF-1R transactivation in VSMC. We have also provided evidence that NO attenuates ET-1-induced ERK1/2, PKB and Pyk2 phosphorylation. Finally, we have established that CaMKII activation stimulates ET-1-evoked protein and DNA synthesis, yet NO attenuates protein synthesis induced by ET-1. Keywords : Endothelin; Hydrogen peroxide; CaMKII; Nitric oxide; Vascular; Protein Kinase B; Extracellular Signal-Regulated Kinase1/2; IGF-1R; Growth.

Nous avons étudié le transcriptome de neuf échantillons d'ARN extraits de cultures primaires de cellules non tumorales de l’épithélium de surface de l’ovaire (NOSE) provenant de quatre donneuses non porteuses de mutation, deux mutées sur BRCA1 et trois sur BRCA2, ainsi que de quatre échantillons d’ARN extraits de cultures primaires de cellules tumorales de l’ovaire (TOV) provenant de trois donneuses porteuses de mutation sur BRCA1 et une sur BRCA2. Nous avons identifié, pour la première fois, les signatures moléculaires associées à la présence d’une mutation de BRCA1 et BRCA2 dans les cellules NOSEs ainsi que la signature associée à la transformation tumorale des cellules NOSEs en TOVs chez les porteuses de mutation de BRCA1. Nous avons également localisé les domaines chromosomiques comportant des gènes corégulés en association avec la présence d’une mutation de BRCA1 dans les cellules NOSEs. Les allèles sauvage et muté de BRCA2 étaient exprimés dans les cellules TOVs provenant des porteuses de la mutation 8765delAG sur BRCA2. Nous avons observé que le niveau d’expression des transcrits de BRCA2 était plus élevé dans les cellules provenant des tumeurs ovariennes les plus agressives chez les femmes porteuses de la mutation 8765delAG sur BRCA2, les transcrits correspondants à l’allèle muté contribuant avec un pourcentage élevé du niveau d’expression total du gène. Le phénotype tumoral observé chez les Canadiennes Françaises porteuses de cette mutation pourrait résulter d’un effet de dosage de l’allèle muté. / We analyzed the transcriptome of nine primary cultures of non-tumor ovarian surface epithelium cells (NOSE) from four non-carriers, two BRCA1 and three BRCA2 carriers, and four primary cultures of tumor ovarian cells (TOV) from three BRCA1 and one BRCA2 carriers. We identified the first molecular signatures associated with the presence of BRCA1 and BRCA2 mutations in NOSEs and the first molecular signature associated with the transformation from NOSEs to TOVs in French Canadian women carriers of BRCA1 mutation. Moreover, we localized some co-regulated chromosomal domains associated with the presence of a BRCA1 mutation in NOSE cells. Wild-type and mutated BRCA2 allelic transcripts were expressed in tumor cells from 8765delAG BRCA2 mutation carriers, with the highest level of BRCA2 transcript expression and the highest contribution of the mutated allele in cells originating from the most aggressive ovarian tumors. The observed phenotype in BRCA2-mutated cells as well as the aggressiveness of the tumor could result from a dosage effect of the BRCA2 mutated allele.

Understanding what to do and how to complete academic tasks is an essential yet complicated academic activity. However, this area has been under-examined. The purpose of this study is to investigate students’ understanding of academic tasks with qualitative and quantitative approaches. Ninety-eight students participated in this study. First, the study explored the kinds of tasks students identified as challenging, the disciplines in which these tasks were situated, the types of structures these tasks had, and challenges found in students’ task analysis activity. Second, the study examined the relationships between students’ task understanding and academic performance. The findings indicated that although students struggled with various tasks, they struggled even more when tasks became less pre-scribed. The results also showed that task understanding was statistically significantly co-related to academic performance and task understanding, particularly, implicit aspect of task understanding, predicted students’ academic performance. The findings supported Hadwin’s (2006) model of task understanding.

The present master paper investigates the challenges which are met while trying to implement the provisions of the directives on professional qualifications into national law. Despite the fact that the directives regulating the recognition of professional qualifications have already been implemented into the national law of the Republic of Lithuania after the new European Parliament and Council directive 2005/36/EC codifying all the existed directives on the recognition of professional qualifications, has been adopted, the competent authorities face new challenges trying to implement the provisions of new directives. Due to this fact, several stages of the implementation of the directives of European Union are distinguished.: the obligations Lithuania had to fulfil before the accession to EU and after the new Directive 2005/36/EC was adopted. The main objective of this paper is to analyse problematical issues regarding the transposition of directives on recognition of regulated professional qualifications into national law. The attempt was made to disclose the main features of the systems regarding recognition of regulated professional qualifications. A great deal of attention is alloted to the analysis of the process of recognition, the presumptions and the development of General system of recognition and Sectoral directives. The main legal documents on professional qualifications as well as provisions of the new law are widely discussed. Currently more and more emphasis... [to full text]

Magistro baigiamajame darbe išanalizuotas pasaulinės gamtinių dujų rinkos veikimo modelis, suskystintų gamtinių dujų terminalų technologijos įtaka pasaulinei gamtinių dujų rinkai bei atskiriems pasaulio regionams priklausomai nuo išvystytos dujų transportavimo infrastruktūros, sukurtas ekonominis SGDT teikiamų valstybės reguliuojamų paslaugų kainų nustatymo modelis Lietuvoje, iškeltos SGDT funkcionavimo ekonominio poveikio gamtinių dujų kainų pokyčiams Lietuvoje (izoliuotoje rinkoje) problemos bei pagal atliktus empirinio tyrimo rezultatus pateikti siūlymai rinkos dalyviams bei kitiems suinteresuotiems asmenims dėl galimų veiksmų pradėjus veikti SGDT 2014 m. gruodžio mėn. Lietuvoje. Pirmajame skyriuje sudaromas pasaulinės gamtinių dujų rinkos veikimo modelis, nagrinėjami ryšiai tarp pagrindinių jo sudedamųjų dalių (gavyba, transportavimas, vartojimas vidaus rinkoje), naujai atrandamų technologijų įtaka kiekvienai iš jų. Antroje dalyje analizuojama Lietuvos gamtinių dujų rinka ir ją supanti teisinė, ekonominė bei politinė aplinkos, aptariamos SGD galimos perspektyvos Lietuvoje. Trečioje dalyje analizuojamas autoriaus kartu su Valstybinės kainų ir energetikos kontrolės komisijos specialistais parengtas ekonominis SGDT teikiamų paslaugų kainos skaičiavimo modelis, aptariama importo kainos prognozavimo metodika, įvertinami pasirinktos metodikos trūkumai ir privalumai, aprašomi kt. metodai, kuriais remiantis ketvirtoje dalyje atliekamas empirinis tyrimas šiame darbe iškeltai... [toliau žr. visą tekstą] / This Master thesis contains: presentation of global natural gas market functioning model and LNGT technology impact on this market, as well as regions according to their infrastructure of gas transportation; creation of economic model for calculating natural gas import prices forecasts and forecasts for prices of regulated LNGT services in Lithuania; presentation of economic problems of LNGT impact on natural gas prices in Lithuania (as an isolated market) and considering the results of empirical research, suggestions of possible actions for market players and third parties after Lithuanian LNGT begins its operations in December, 2014. The first part of the thesis includes examination of global natural gas market functioning, the relations between its main components (extraction, transportation, consumption in domestic markets) and influence of the new technologies for each of them. The second part analyses Lithuanian natural gas market: its legal, economic and political environment, as well as presents LNG perspectives in Lithuania. The third part consists of introducing the economic LNGT services’ price model which was created by author of this thesis in collaboration with specialists of National control commission for prices and energy, also the methodology of calculating forecasts for natural gas import prices, its advantages and disadvantages, as well as other methods which were employed to solve the main problem of the Master thesis in the last part of this work.

Background: Prostitution has been documented in most societies, although the context in which it occurs may vary greatly. In Queensland, Australia, sex workers can operate from legal brothels or privately but all other sectors of the sex industry are prohibited. It is assumed that regulation of the sex industry through legalization leads to better health and social outcomes for sex workers and their clients. However, this assumption has rarely been subjected to empirical scrutiny. Aims: This research examined the occupational health and safety of female sex workers in Queensland and explored the relationship between legislative change, workplace violence, mental health and job satisfaction. Sex workers interviewed in 2003 (after legalisation) were compared to a prior study of this population conducted in 1991 (before official regulation of the sex industry). Further, in-depth analysis of the 2003 cohort compared sex workers employed in legal and illegal sectors, to assess violence, health status and job satisfaction. Methods: Cross-sectional, convenience sampling was used to collect data from female sex workers in 2003. This data was compared with data collected earlier (in 1991) and explored differences in the two samples using bivariate analysis. Similar recruitment strategies on both occasions were used to recruit women from all known sectors of the Queensland sex industry. The 1991 comparison sample (Boyle et al. 1997) included 200 women (aged between 16 and 46 years), and in 2003, 247 women (aged 18 to 57) participated. The 2003 sample included workers from legal brothels (n=102), private sole-operators (n=103) and illegal street-based sex workers (n=42). Using data collected in 2003, this study assessed the relationship between physical and mental health and job satisfaction and two main independent variables, i.e., current work sector and recent workplace violence. Bivariate analysis of physical health and independent variables showed no significant relationships and therefore further analysis was not undertaken. However, analysis of mental health and job satisfaction showed complex interactions between multiple variables and therefore linear modeling was performed to adjust for confounding. Results: Analysis of the 1991 and 2003 samples showed little apparent change over time in self-reported sexually transmitted infections (STIs). There were substantial changes over time in the types of sexual services being provided to clients, with the 2003 sample more likely to provide 'exotic' services. Violence experienced ever in their lifetime differed; in 1991, 29% reported having ever been raped compared with 42% in 2003 (p= &lt0.01). In 2003, 50% of illegal sex workers reported having ever been raped by a client compared with 12% of private sex workers and 3% of brothel-based sex workers (p=&lt0.01). Overall, the sex workers reported roughly equivalent job satisfaction to Australian women. A desire to leave the sex industry was most strongly correlated with reduced job satisfaction (p=&lt0.01). Satisfaction was also relatively low among those whose family was not aware of their sex work (p=&lt0.01). Similarly, the mental and physical health of this sample was comparable to age-matched women from the general population. Wanting to leave the sex industry was most strongly associated with poor mental health (p=&lt0.01), as was recent sexual or physical assault by a client (p=0.06) and the woman's main work sector (p=0.05). Illegal sex workers reported substantially lower mental health scores than their counterparts in legal sex work. Conclusions: Self-reported STI diagnosis was high in these samples but the prevalence appears not to have changed over time. Comparing 2003 to 1991, there were trends towards safer and more diverse sexual practices. It is likely the sex industry has 'professionalized' and now includes more sex workers providing specialist, 'exotic' services. This sample of female sex workers reported high rates of violence, with those working illegally at greatest risk. Analysis suggests a complex interaction between variables contributing to mental health and job satisfaction. In general, it appears that the majority of sex workers enjoyed at least as much job satisfaction as women working in other occupations. It also appears that this sample had equivalent mental health to women from the general population, although the sub-group of illegal workers generally had poorer health. Job satisfaction and the extent of workplace hazards (especially risk of violence) were also strongly associated with different sectors of the sex industry. It is probable that legalisation has benefited some (perhaps most) but there are health and safety concerns for those outside the legal framework. Legislative reform should focus on violence prevention, promoting reporting of violent events to police, and further exploration of the impact of legislation on the health of workers in the sex industry.

The business environment of the 21st century is rapidly changing. Customers demand are diversifying, governments enforce stricter environmental regulations and start-ups are entering with disruptive business models. Traditional industrial organisations need to adapt to compete on a market revolving around time-to-market actions. One solution for this is to do an agile transformation. This thesis investigates the agile transformation process of traditional organisations through a case study. The objective is to identify find the main success drivers and key challenges in stated transformation. The research was designed to do a qualitative, interview based case study in the automotive and aerospace industries involving four companies from an interpretivistic paradigm. In addition, two companies from insurance and banking and four agile coaches were also part of the case study to establish generalisability. The theoretical and empirical findings succeed to find three main success drivers: management support, identifying the “Why?” and “How?”, and three key challenges: structural legacies, cultural legacies and configuration of transformation process. Additionally, it was found that current transformations in the selected industries are diverging from change management theories, which emphasises a greater focus on changing mindset, behaviour and culture. Finally, the study contributes with actions as to help companies pursuing agile transformation as well identifying a continuous need for research of agile methods in non-software environments. / Marknaden har under 2000-talet ändrats snabbt. Kunders krav på produkter ökar, statliga miljöregleringar träder i kraft och start-ups går in med disruptiva affärsmodeller. I detta läge behöver traditionella industribolag anpassa för att kunna konkurrera på den nya marknaden som kräver en kortare tid till marknaden. En lösning på detta problem är en agil transformation. Den här uppsatsen undersöker de agila transformationsprocesserna genom en fallstudie. Målsättningen är att identifiera de huvudsakliga framgångsfaktorer samt utmaningar som återfinns i nämnda transformationer. Forskningen designades genom en kvalitativ intervjufallstudie hos fyra företag inom vägfordons- och flygplansindustrin från ett interpretivistiskt forskningsparadigm. Vidare deltog två företag från försäkring och bank samt fyra agila coacher för att kunna etablera generaliserbarhet. De teoretiska och empiriska ramverken lyckades hitta tre stycken framgångsfaktorer: ledarstöd, identifierandet and “Varför?” samt ”Hur?”, samt tre primära utmaningar: strukturella och kulturella arv samt konfigurationen av transformationsprocessen. Vidare fann studien att de nuvarande transformationerna som finns i valda branscher divergerar från förändringsledningsteorierna, som i sin tur betonar ett större fokus på förändring av mindset, beteende och kultur. Slutligen bidrar denna studie med föreslagna åtgärder som hjälper företag som genomgår en transformation och identifierar ett fortsatt behov av att forska kring användandet av agila metoder in icke-mjukvaruområden.

Thesis (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Not embargoed. Vita. Bibliography: 97-109.

Themes my diploma is ,,Bonds trading on the capital market in the Czech Republic``. In introductory part of my thesis I deal with theoretic summary and functioning of capital market, regulation and supervision of capital market and individual subjects acting in this market. In more detail I deal with describeing the Prague Stock Exchange and company RM-System. I further define conception the bond and I describe long bonds, theirs basic kinds and conceptions used in the bonds. I also allude to series of different kinds of the bonds, that the offer on the international markets. Next part of my thesis is aimed to describe the development of the Czech market of bonds. I analyze the development of bonds trading in the last of several years on the regulated markets and the OTC-markets in the Czech Republic. In the close of my thesis I analyze the development of bonds trading on the Czech market of bonds in comparasion with Slovakian, Polish and Hungarian markets. This analysis was take in on comparision of the Stock Exchange of chosen countries.

Circadian system of mammals is generated in suprachiasmatic nuclei of hypothalamus. This system is synchronized with light conditions through phase shifts that occur after light exposition during the subjective night. Recent studies have shown that activation of endocannabinoid receptors attenuates the light-induced phase shifts and influences the ability of circadian system to light entrainment. The aim of this work is to examine this influence on behavioral level and on light-reactive cellular processes within the suprachiasmatic nuclei. Our results show that the activation of endocannabinoid system via CB1 receptor agonist modulates the light-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the expression of c-Fos protein in neurons of suprachiasmatic nuclei in the rat's brain; these cellular processes correlate with the attenuation of light entrainment. Keywords: circadian system, suprachiasmatic nuclei, light entrainment, endocannabinoid system, CB1 receptors, extracellular signal-regulated kinase 1/2, ERK1/2, c-Fos