No / Purpose: Using arguments from the regulatory focus and upper echelons theories, this paper aims to examine the impact of a chief executive officer’s (CEO’s) regulatory foci (i.e. promotion and prevention focus) on small- and medium-sized enterprises’ (SMEs’) level of innovativeness and how these relationships are jointly moderated by intense competition. Design/methodology/approach: The empirical analysis draws on survey data gathered from 257 SMEs in Ghana. Findings: The study findings indicate that a CEO’s level of promotion focus positively affects the firm’s engagement in innovation, while a CEO’s prevention focus is negatively associated with the firm’s innovativeness. The positive association between a CEO’s promotion focus and a firm’s innovativeness is enhanced under conditions of intense competition. Additionally, the negative relationship between prevention focus and firm-level innovativeness is attenuated under intense competition. Research limitations/implications: This study relied on a single informant and also used subjective measures for the dependent variable. As such, individual respondents might have biased perspectives on firm-level product innovativeness. Future studies may use multiple informants to examine the causal links of the variables. Practical implications: The study’s findings provide managers with a deeper understanding of how to achieve superior firm-level product innovation. The understanding of this issue can promote the development and maintenance of further entrepreneurial ventures in emerging economies. Originality/value: The paper has a strong theoretical value as it pioneers research on the effect of CEOs’ regulatory foci on firm-level innovativeness in competitive environments.

Yes / Purpose The purpose of this article was to examine the joint effects of regulatory focus, entrepreneurial persistence, and institutional support on new venture performance. Design/methodology/approach This paper uses a random survey approach to sample 204 new ventures from Ghana. The moderated mediation method was used to analyze the survey data. Findings The findings from this paper show that entrepreneurs’ promotion focus positively relates to persistence whiles prevent focus negatively influences persistence. Besides, persistence mediates the link between regulatory focus (promotion and prevention focus) and new venture performance. These relationships are positively moderated by perceived institutional support. Research limitations/implications Using data from only the manufacturing sector in Ghana limits the generalisability of this paper. Also, persistence was not observed or measured directly in this paper but was only used as a self-reporting variable that captures an individual’s tendency to persist. Originality/value The contribution of this paper is threefold. First, this paper contributes to regulatory focus literature by enhancing our knowledge of how self-regulation could help explain entrepreneurial decision-making. Second, this paper broadens self-regulation literature by adding institutional context as a moderating variable. Third, this paper helps clarify the potential role of persistence in entrepreneurship.

No / 1 In this study we examined the signalling events that regulate lipopolysaccharide (LPS)-stimulated induction of interferon regulatory factor (IRF)-1 in human umbilical vein endothelial cells (HUVECS). 2 LPS stimulated a time- and concentration-dependent increase in IRF-1 protein expression, an effect that was mimicked by the cytokine, tumour necrosis factor (TNF)-¿. 3 LPS stimulated a rapid increase in nuclear factor kappa B (NFKB) DNA-binding activity. Preincubation with the NFKB pathway inhibitors, N-¿-tosyl-L-lysine chloromethyl ketone (TLCK) or pyrrolidine dithiocarbamate (PDTC), or infection with adenovirus encoding IKB¿, blocked both IRF-1 induction and NFKB DNA-binding activity. 4 LPS and TNF¿ also stimulated a rapid activation of gamma interferon activation site/gamma interferon activation factor (GAS/GAF) DNA-binding in HUVECs. Preincubation with the Janus kinase (JAK)-2 inhibitor, AG490 blocked LPS-stimulated IRF-I induction but did not affect GAS/ GAF DNA-binding. 5 Preincubation with TLCK, PDTC or infection with I¿Ba adenovirus abolished LPS-stimulated GAS/GAF DNA-binding. 6 Incubation of nuclear extracts with antibodies to RelA/p50 supershifted GAS/GAF DNA-binding demonstrating the involvement of NF¿B isoforms in the formation of the GAS/GAF complex. 7 These studies show that NF¿B plays an important role in the regulation of IRF-1 induction in HUVECs. This is in part due to the interaction of NF¿B isoforms with the GAS/GAF complex either directly or via an intermediate protein.

In each individual cell, there are many signaling pathways that may interact or cross talk with each other. Especially, some can sense the same signal and go through different pathways but eventually converge at some points. Therefore repetitive signal stimulations may result in intricate cell responses, among which the priming effect has been extensively studied in monocytes and macrophages as it plays an unambiguously crucial role in immunological protection against pathogen infection. Priming basically describes the phenomena that host cells can launch a dramatically enhanced response to the second higher dose of stimulus if cells have been previously treated with a lower dose of identical stimulus. It was reported to be associated with many human immune diseases (such as rheumatoid arthritis and hepatitis) that are attracting more and more researches on the priming effect. It is undoubtable that many genes are involved in this complicated biological process. Microarray is one of the standard techniques that are applied to do the transcriptome profiling of cells under repetitive stimuli and reveal gene regulatory networks. Therefore a well-established pipeline to analyze microarray data is of special help to investigate the underlying mechanism of priming effect. In this research, we aimed to design a strategy that can be used to interpret microarray data and to propose gene candidates that potentially participate in priming effect. To confirm our analysis results, we used a detailed mathematical model to further demonstrate the mechanism of a specific case of priming effect in a computational perspective. / Master of Science

Les Iron Regulatory Proteins 1 (IRP1/2) sont des protéines cytosoliques qui contrôlent l’homéostasie du fer chez les mammifères. Elles régulent la concentration de fer intracellulaire au niveau post-transcriptionnel, en interagissant spécifiquement avec des motifs appelés iron responsive élément (IREs). Ces motifs sont localisés dans les régions non traduites des ARNm codant notamment pour la ferritine (Ft), la ferroportine (Fpn) et le récepteur de la transferrine (TfR1). L’IRP1 est une protéine bifonctionnelle, majoritairement exprimée sous une forme contenant un centre [4Fe-4S] qui présente une activité aconitase. Les deux activités de l’IRP1 (aconitase/trans-régulateur) s’excluent mutuellement par la présence ou non du centre Fe-S. L’IRP2 est exprimée constitutivement sous une forme liant les IREs. Le monoxyde d’azote (NO), une importante molécule de signalisation impliquée dans les défenses immunitaires, cible le centre Fe-S de l’IRP1 et permet la conversion de l’IRP1 de sa forme aconitase vers sa forme liant les séquences IREs. Il a également été rapporté que l’IRP2 détecterait NO, cependant la fonction intrinsèque de l’IRP1 et de l’IRP2 dans le contrôle du métabolisme du fer intracellulaire en réponse à NO reste à ce jour non élucidée. Dans cette étude, nous avons identifié le régulateur principal du métabolisme du fer intracellulaire en réponse à NO, en utilisant des modèles de souris déficients pour les gènes IRP1 et/ou IRP2 et testé la contribution de la tension en oxygène dans cette régulation. Ainsi, nous avons exposé des macrophages primaires issus de la moelle osseuse de souris Irp1-/-, Irp2-/- et de souris Irp1-/- Irp2-/- de la lignée macrophagique à une source de NO, sous différentes tensions en oxygène. Les activités IRPs, l’expression des gènes Ft, Fpn et TfR1 ainsi que l’activité d’une protéine à centre Fe-S (l’aconitase mitochondriale) ont été mesurées après fractionnement cellulaire. Nous avons montré qu’en normoxie, la conversion de l’aconitase cytosolique en apo-IRP1 par NO est entièrement responsable de la régulation post-transcriptionnelle des ferritines (L-Ft et H-Ft), de la Fpn et du TfR1. En augmentant le transport du fer intracellulaire et en diminuant le stockage et l’export, l’activation de l’IRP1 par NO servirait à maintenir des taux de fer intracellulaire suffisants pour alimenter la biogenèse des centres Fe-S après l’arrêt des flux de NO. En effet, nous observons une restauration efficace de l’activité de l’aconitase mitochondriale dans les macrophages de souris sauvage alors qu’elle est bloquée dans les macrophages de souris Irp1-/-. De plus, l’IRP1 activée par NO, permet également de diminuer les taux de L- et H-Ft, anormalement élevée dans les macrophages de souris Irp2-/-. Nous montrons que le NO endogène active l’IRP1 sous sa forme trans-régulatrice alors qu’il tend à diminuer l’activité de l’IRP2. Néanmoins, l’IRP1 reste le régulateur principal des ferritines en conditions de normoxie. En condition hypoxique, les deux IRPs semble coopérer pour inhiber la traduction des ferritines car dans les macrophages Irp1-/-exposés à NO, l’IRP2 stabilisée est suffisante pour inhiber la traduction de la L- et H-Ft et ceci malgré l’activation transcriptionnelle des gènes de la L- et H-Ft. Concernant la régulation du TfR1 par NO et en hypoxie, TfR1 est principalement régulé par une voie transcriptionnelle dominant largement la voie post-transcriptionnelle impliquant l’IRP1. Le facteur de transcription HIF-1 alpha pourrait être le régulateur critique dans cette régulation. En conclusion, nous montrons dans cette étude, comment le regulon IRP participe à la régulation du métabolisme du fer intracellulaire en réponse à NO et son étroite connexion avec la concentration en oxygène. Nos résultats soulignent l’importance d’explorer davantage le rôle de l’IRP1 dans des situations inflammatoires in vivo, où les tissus peuvent être exposé à un microenvironnement non hypoxique. / Iron Regulatory Protein 1 (IRP1) and 2 (IRP2) are two cytosolic regulators of mammalian cellular iron homeostasis. IRPs post-transcriptionally modulate expression of iron-related genes by binding to specific sequences, called Iron Regulatory Elements (IREs), located in the untranslated regions (UTR) of mRNAs. Either of the two IRPs inhibits translation when bound to the single 5’UTR IRE in the mRNA encoding proteins of iron export (ferroportin - Fpn) and storage (ferritin - Ft) or prevents mRNA degradationwhen bound to the multiple IREs within the 3’UTR of the mRNA encoding the transferrinreceptor 1 (TfR1) - iron uptake molecule. The IRE-binding activity of both IRPs respondsto cellular iron levels, albeit via distinct mechanisms. IRP1 is a bifunctional protein, whichmostly exists in its non IRE-binding, [4Fe-4S] aconitase form and can be regulated by apost-translational incorporation or removal of the Fe-S cluster. In contrast to IRP1, IRP2 isnot able to ligate an Fe-S cluster, and its IRE-binding activity is determined by the rate ofits proteasomal degradation. Although both IRP1 and IRP2 can regulate cellular ironhomeostasis, only mice lacking IRP2 were shown to display iron mismanagement in mosttissues. This could be explained by the fact that IRP1 exists mostly in its non IRE−binding,aconitase form under physiological oxygen conditions (3-6%). Interestingly, nitric oxide(NO), an important signalling molecule involved in immune defence, targets the Fe-Scluster of IRP1 in both normoxia and hypoxia, and converts IRP1 from aconitase to anIRE-binding form. It has also been reported that IRP2 could sense NO, but the intrinsicfunction of IRP1 and IRP2 in NO−mediated regulation of cellular iron metabolism hasremained a matter of controversy. In this study, we took advantage of mouse models ofIRP deficiency to define the respective role of IRP1 and IRP2 in the regulation of cellulariron metabolism by NO and assess the contribution of oxygen tension on the regulation.Therefore, we exposed bone marrow-derived macrophages (BMMs) from Irp1-/-, Irp2-/- andmacrophage specific double knockout mosaic mice (Irp1/2-/-) to exogenous andendogenous NO under different oxygen conditions (21% O2 for normoxia and 3-5% forhypoxia experiments) and measured IRPs activities, iron-related genes expression andactivity of Fe-S cluster protein – mitochondrial aconitase. We showed that in normoxia, thegenerated apo-form of IRP1 by NO was entirely responsible for the post-transcriptionalregulation of TfR1, H-Ft, L-Ft and Fpn. Moreover, by increasing iron uptake and reducingiron sequestration and export, NO−dependent IRP1 activation served to maintainadequate levels of intracellular iron in order to fuel the Fe−S biosynthetic pathway, asdemonstrated by the efficient restoration of the mitochondrial Fe−S aconitase, which wasprevented under IRP1 deficiency. Furthermore, activated IRP1 was potent enough todown-regulate the abnormally increased L-Ft and H-Ft protein levels in Irp2-/-macrophages. Endogenous NO activated IRP1 IRE-binding activity and tended todecrease IRP2 IRE-binding activity. Nevertheless, IRP1 was the predominant regulator offerritin in those conditions. In hypoxia, in Irp1+/+ and Irp2+/+ macrophages exposed to NO,both stabilized IRP2 and NO-activated IRP1 seemed to cooperate to inhibit ferritinsynthesis. However, in Irp1-/- cells, IRP2 stabilized in hypoxia was sufficient to inhibit LandH-Ft synthesis despite the concomitant increase of corresponding mRNAs.Interestingly, TfR1 was shown to be predominantly regulated at the transcriptional level byNO in hypoxia, in which HIF-1 alpha may be the critical regulator. In conclusion, we revealin this study how the IRP regulon participates in the regulation of cellular iron metabolismin response to NO and its intimate interplay with the oxygen pathway. The findingsunderlie the importance to further explore the role of IRP1 in inflammation in vivo, in nonhypoxictissue microenvironments.

Small developing states can use proper regulatory frameworks in policy and sector development to implement efficiency and consumer safeguards to the sector. However, sufficient research on the impact of telecommunications regulatory institutions on micro economies has not been conducted. Capture theory was used as the theoretical lens for this thesis. In doing so, a quantitative analysis was done using, cross-sectional pooled time series to determine how an independent telecommunications regulator impacted the telecommunications sector in the English-speaking Caribbean. All the data acquired for analysis were secondary yearly data collected from the International Telecommunications Union (ITU) from 1993 to 2012. Specifically, this study examined how prices, investment, infrastructure, and competition in the telecoms sector are affected by the type of regulatory regime (independent or non independent ) for fixed line and mobile services. Results indicate that the type of regulatory regime has a statistically significant impact on fixed line services and price of the telecommunications sector (p < .0001). However, this regulation was absent in other areas such as cellular services, broadband usage, telecoms investment and competition. The potential for positive social change is tied to recommendations specific to developing countries to ensure their regulators have autonomy in making decisions regarding the volume, quality and costs of telecommunications services. Legislation must minimize any overlap in the roles of policy makers, legislators, administrators and regulators to ensure that the regulatory framework addresses the particulars conditions of the country in which it operates.

Based upon critical political economy and Marxist theory of the state, this thesis attempts to understand the neoliberal form of the capitalist state in Turkey. While doing this, it puts the establishment of independent regulatory agencies (IRAs) into the framework of the claim of de-politicization and redefined form of the separation of the political and the economic under neoliberalism. It argues that neoliberalism solved its crisis and settled through each financial crisis, as a result of which the state is restructured. Acceleration of the delayed neoliberal transformation in Turkish agriculture through crises provides a ground to this argument. This study focuses on Tobacco and Alcohol Market Regulatory Authority (TAPDK) as an IRA, which enables analysis of neoliberal transformation of both agriculture and the state. Besides / the thesis includes an analysis of the Tobacco Law, which established TAPDK, since it is accepted that law is a significant mediation of the settlement of neoliberal hegemony. Furthermore, the thesis utilizes from in-depth interviews with not only officials from TAPDK, but also previous workers of tobacco and cigarette producing factories and tobacco farmers in order to find out how the labouring classes experienced the transformation. This contributes to the development of an analysis of the state as an arena of class struggle. Therefore / it is asserted, in this thesis, that TAPDK exemplifies the mediation of capital-labour relations by the state in tobacco sector, and appears as an arena of class struggle, as opposed to the discourse of the purification of economic management from politics.

Diss. (sammanfattning) Stockholm : Karol. inst., 2007. / Härtill 3 uppsatser.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p. 96-110.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 92-107).