Potential gains from economic integration as impetus for regional integration: a comparison of ASEAN, ASEAN+3 and EAC

Political economy theory usually emphasizes the impact of economic interdependence within a region for successful and dynamic regional integration. According to that, participating economies must constitute mutual export markets and investment destinations to exploit gains from intraregional trade and investment. As a consequence the integration process receives positive feedback from member states and furthers progress in regional integration. However, this paper argues that regional integration in Southeast Asia is at least as dependent on economic cooperation and positive feedback from external partner countries and regions as it is on internal economic effects. The argument will be underscored by intra- and interregional trade and investment analysis of the Association of Southeast Asian Nations (ASEAN). The ASEAN made crucial steps towards regional integration in the last decade by establishing the ASEAN Free Trade Area, promoting the ASEAN Investment Area and negotiating and implementing Free Trade Agreements (FTAs) with major trade partners. Due to the market patterns in the ASEAN the intraregional trade and investment stagnates at a low level. As a result it is argued that regional integration as effect of economic integration in Southeast Asia is primarily dependent on widening economic cooperation. It will be indicated that at the current status of economic development in the ASEAN, interaction with China, Japan and Korea (ASEAN+3) is more promising in evoking positive feedback than interaction with India, Australia and New Zealand (which constitute together with the ASEAN+3 the East Asian Community, a proposed trade block)." (author's abstract

Mechanismen institutioneller Dynamiken. Eine vergleichende Prozessanalyse der Entwicklung des ASEAN-Handelsregimes

Die allgemeine Zielsetzung dieser Arbeit besteht darin, die Dynamik internationaler Institutionen theoretisch und empirisch zu untersuchen. Dazu wird in dieser Arbeit ein handlungstheoretisches Argument entwickelt, das strukturinduzierte Interessen und akteursspezifische Ideen als kombinatorische Einflussfaktoren für die Präferenzbildung von Staaten hinsichtlich institutioneller Dynamiken konzipiert. Die kausale Logik des Argumentes wird in zwei Mechanismen abgebildet: Der Mechanismus der Präferenz-Destabilisierung enthält Aussagen darüber, wie Veränderungen relevanter Strukturen die Präferenz eines Staates hinsichtlich einer Institution beeinflussen. Mit dem Mechanismus der Präferenz-Delegitimierung wird hingegen plausibilisiert, wie Veränderungen von Ideen die Präferenz eines Staates hinsichtlich einer Institution beeinflussen. Schließlich wird von der kombinatorischen Wirkung dieser Mechanismen auf die Ausprägung institutioneller Dynamiken geschlossen, die Staaten anstreben. In der empirischen Analyse wird die Entwicklung des ASEAN-Handelsregimes seit seiner Gründung 1977 untersucht. Dazu wird in einer Kombination aus qualitativem Fallvergleich und Prozessanalyse analysiert, welche Variablen kausalen Einfluss haben und ob die Mechanismen entsprechend der formulierten Annahmen wirken.The aim of the dissertation is to better understand the empirical phenomena of institutional dynamics in international politics. To this end, the author develops an action-based argument for institutional change. Within this argument, the decisive factor is the match of structural-induced interests and actor-based ideas. In situations of “structure-actor-mismatches”, actors tend to reduce dissonances and, as a consequence, change their preferences over institutional outcomes. This in turn impacts the status quo institution. Without mismatch, there will be neither dynamic at the actor level nor at the institutional level. Based on this argument, the author develops two causal mechanisms to explain the causality underlying this hypothesis theoretically. The mechanism of preference-destabilizing argues how changes in relevant structures impact states preferences. The mechanisms of preference-delegitimizing reasons how ideational changes influence states preferences. The empirical analysis focuses on international institutions in Southeast Asia, namely the development of the ASEAN trade regime since its inception in 1977. A combination of qualitative case comparison and process-tracing is applied in order to examine the causality of the variables and the logic of the mechanisms

Viable adhered Staphylococcus aureus highly reduced on novel antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site infection (SSI)

Background Surgical sutures can promote migration of bacteria and thus start infections. Antiseptic coating of sutures may inhibit proliferation of adhered bacteria and avoid such complications. Objectives This study investigated the inhibition of viable adhering bacteria on novel antimicrobially coated surgical sutures using chlorhexidine or octenidine, a critical factor for proliferation at the onset of local infections. The medical need, a rapid eradication of bacteria in wounds, can be fulfilled by a high antimicrobial efficacy during the first days after wound closure. Methods As a pretesting on antibacterial efficacy against relevant bacterial pathogens a zone of inhibition assay was conducted with middle ranged concentrated suture coatings (22 mu g/cm). For further investigation of adhering bacteria in detail the most clinically relevant Staphylococcus aureus (ATCC (R) 49230 (TM)) was used. Absorbable braided sutures were coated with chlorhexidine-laurate, chlorhexidine-palmitate, octenidine-laurate, and octenidine-palmitate. Each coating type resulted in 11, 22, or 33 mu g/cm drug content on sutures. Scanning electron microscopy (SEM) was performed once to inspect the coating quality and twice to investigate if bacteria have colonized on sutures. Adhesion experiments were assessed by exposing coated sutures to S. aureus suspensions for 3 h at 37 degrees C. Subsequently, sutures were sonicated and the number of viable bacteria released from the suture surface was determined. Furthermore, the number of viable planktonic bacteria was measured in suspensions containing antimicrobial sutures. Commercially available sutures without drugs (Vicryl (R), PGA Resorba (R), and Gunze PGA), as well as triclosan-containing Vicryl (R) Plus were used as control groups. Results Zone of inhibition assay documented a multispecies efficacy of novel coated sutures against tested bacterial strains, comparable to most relevant S. aureus over 48 hours. SEM pictures demonstrated uniform layers on coated sutures with higher roughness for palmitate coatings and sustaining integrity of coated sutures. Adherent S. aureus were found via SEM on all types of investigated sutures. The novel antimicrobial sutures showed significantly less viable adhered S. aureus bacteria (up to 6.1 log) compared to Vicryl (R) Plus (0.5 log). Within 11 mu g/cm drug-containing sutures, octenidine-palmitate (OL11) showed the highest number of viable adhered S. aureus (0.5 log), similar to Vicryl (R) Plus. Chlorhexidine-laurate (CL11) showed the lowest number of S. aureus on sutures (1.7 log), a 1.2 log greater reduction. In addition, planktonic S. aureus in suspensions were highly inhibited by CL11 (0.9 log) represents a 0.6 log greater reduction compared to Vicryl (R) Plus (0.3 log). Conclusions Novel antimicrobial sutures can potentially limit surgical site infections caused by multiple pathogenic bacterial species. Therefore, a potential inhibition of multispecies biofilm formation is assumed. In detail tested with S. aureus, the chlorhexidine-laurate coating (CL11) best meets the medical requirements for a fast bacterial eradication. This suture coating shows the lowest survival rate of adhering as well as planktonic bacteria, a high drug release during the first-clinically most relevant-48 hours, as well as biocompatibility. Thus, CL11 coatings should be recommended for prophylactic antimicrobial sutures as an optimal surgical supplement to reduce wound infections. However, animal and clinical investigations are important to prove safety and efficacy for future applications

Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists

Motogenic and morphogenic activity of epithelial receptor tyrosine kinases

Abstract. Receptor tyrosine kinases play essential roles in morphogenesis and differentiation of epithelia. Here we examined various tyrosine kinase receptors, which are preferentially expressed in epithelia (c-met, c-ros, c-neu, and the keratin growth factor [KGF] receptor), for their capacity to induce cell motility and branching morphogenesis of epithelial cells. We exchanged the ligand-binding domain of these receptors by the ectodomain of trkA and could thus control signaling by the new ligand, NGF. We demonstrate here that the tyrosine kinases of c-met, c-ros, c-neu, the KGF receptor, and trkA, but not the insulin receptor, induced scattering and increased motility of kidney epithelial cells in tissue culture. Mutational analysis suggests that SHC binding is essential for scattering and increased cell motility induced by trkA. The induction of motility in epithelial cells is thus an important feature of various receptor tyrosine kinases, which in vivo play a role in embryogenesis and metastasis. In contrast, only the c-met receptor promoted branching morphogenesis of kidney epithelial ceils in three-dimensional matrices, which resemble the formation of tubular epithelia in development. Interestingly, the ability of c-met to induce morphogenesis could be transferred to trkA, when in a novel receptor hybrid COOH-terminal sequences of c-met (including Y14 to Y16) were fused to the trkA kinase domain. These data demonstrate that tubulogenesis of epithelia is a restricted activity of tyrosine kinases, as yet only demonstrated for the c-met receptor. We predict the existence of specific substrates that mediate this morphogenesis signal. I N the last decade, a large variety of receptor tyrosine kinases were molecularly characterized (for reviews see Ultrich and Schlessinger, 1990; van der Geer et al., 1994). Several of these receptors were first discovered because of their transforming potential and were therefore associated with mediating mitogenic signals (Cooper et al.

Novel High Efficient Coatings for Anti-Microbial Surgical Sutures Using Chlorhexidine in Fatty Acid Slow-Release Carrier Systems

Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Antimicrobial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the "gold standard'' in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 mu g/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 mg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 mg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures