Institutional Conditionality and State Compliance: The Czech and Slovak Accession to NATO and the EU

This dissertation studies the interaction between international institutions and nation states. More specifically, it examines how the membership conditionality of the North Atlantic Treaty Organization (NATO) and the European Union (EU) was adopted by candidate states. It uses the Czech and Slovak accessions to NATO and the EU to argue that, in order to understand the external phenomenon of conditionality, we need to study its effects within states. Critical to this process is national leadership. National leaders determine whether and how conditionality is implemented. Furthermore, this dissertation asserts that successful compliance with NATO and EU conditionality is decisively determined by the extent to which leaders perceive compliance with institutional norms and rules to be in their interest, as well as by the extent to which their normative stance is aligned with the norms contained within NATO and EU conditionality. Elites favorably disposed towards membership are a sine qua non for successful compliance with conditionality. The case studies offer a detailed analysis of the dynamics of the accession process in the Czech Republic and Slovakia. What becomes apparent is the failure of either a purely rationalist or a purely constructivist explanation to capture the empirical phenomenon of compliance with conditionality. Neither approach can adequately accommodate the mix of material and ideational preferences that drives a state\u27s response to conditionality. This dissertation therefore advocates the employment of a more comprehensive analytical approach that transcends the traditional dichotomy between the two schools of thought and takes both rational and normative motivations of state behavior into consideration in order to explain the complexity of state behavior

LONG-TERM SURVIVAL OF THE TRANSPLANTED KIDNEY AND THE CLINICAL RELEVANCE OF DONOR-SPECIFIC ANTIBODIES

The aim of our study was to evaluate the relevance of donor-specific antibodies (DSA) as defined by solid-phase single-antigen (SA) assays for predicting long-term graft survival after kidney transplantation. Sera from 132 kidney transplant recipients were retrospectively tested before, 3, 6 and 12 months after transplantation. The incidence of rejection and graft survival was followed up for 7 years. We found 29 episodes of acute cellular rejection (CR), 21 cases of antibody-mediated rejection (AMR) and 18 graft failures due to immunological reasons. Pre-transplant DSA and DSA three months after transplantation correlated with an increased rate of AMR and impaired graft function. After the fourth year, recipients with persistent DSA were at a higher risk of graft failure (p = 0.0317). Antibody specificity was prevailingly to HLA class I antigens (66.6% DSA, 75% non-DSA). During the first year after transplantation, the number of patients with non-DSA decreased (30.3% to 10.7%), while, due to de novo production of antibodies, the number of DSA positive patients remained constant. Conclusion: Detection of antibodies to HLA antigens using solid-phase assays, especially single-antigen bead technology before and three months after transplantation is predictive for increased incidence of antibody-mediated rejection and impaired long-term kidney graft survival

From a Biomarker to Targeting in a Proof-Of-Concept Trial

Background There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. Methods In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. Results TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6–98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. Conclusions In conclusion, our novel fast-track TAC- monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full–scale study will be needed to confirm our findings. Trial Registration EudraCT Number: 2006-003110-1

Assessment of somaclonal variation in somatic embryo-derived plants of yacon [ Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson] using inter simple sequence repeat analysis and flow cytometry

Background: Yacon ( Smallanthus sonchifolius ) is a root crop native to the Andean region. Low sexual reproductive capacity is amajor constraint facing the genetic breeding of this crop. Biotechnological techniques offer alternative ways to widen genetic variability. We investigated somaclonal variation in regenerants of yacon derived from in vitro somatic embryogenesis using simple sequence repeat (ISSR) analysis and flow cytometry. Results: Twenty tested ISSR primers provided a total of 7848 bands in 60 in vitro regenerants and control plant. The number of bands for each primer varied from3 to 10, and an average of 6.95 bands was obtained per ISSR primer. Eight primers were polymorphic and generated 10 polymorphic bands with 7.19% mean polymorphism. ISSR analysis revealed genetic variability in 6 plants under study. These regenerants had Jaccard's distances 0.104, 0.020, 0.040, 0.106, 0.163 and 0.040. Flow cytometric analysis did not reveal changes of relative nuclear DNA content in regenerants suggesting that the plants obtained via somatic embryogenesis had maintained stable octoploid levels. Conclusions: Our findings show that indirect somatic embryogenesis could be used in yacon improvement to widen genetic variability, especially when low sexual reproductive capacity hinders classical ways of breedin

Verbal Aggressiveness in Communication in Media and Online. A Case Study of the TV Cooking Show »Spread«

The paper discusses verbal aggressiveness and (im)politeness in media and online communication. The analysis focuses on transcriptions of communicative acts by participants of the TV reality Spread! ("Prostřeno!", a Czech version of the programme Come Dine with me) and viewers' comments in related online discussions. The analysis indicated that the use of face-threatening acts was determined by a type of communicative interaction and interlocutors' social roles. Striving to construct a positive self-image, the participants in the show did not take the risk of losing their face due to usage of derogatory or vulgar expressions in face-to-face inter- actions. The anonymous online discussions, on the contrary, did not pose any risk for the positive faces of the speakers; therefore, the interlocutors showed clear tendency to either appreciate and support, or attack the contestants as well as other speakers.

Flavin photocatalysis

Thanks to rapid development in the last decades, flavins have been recognized as promising photoactive compounds to design new valuable synthetic methodologies based on photoredox catalysis. The review summarizes general photochemical properties of flavins as well as their early applications in transformations mediated by visible light. Special attention has been paid to the catalyst design for benzylic oxidations as well as to recent flavin applications, for example in E/Z-isomerization, [2+2] cycloaddition, cycloelimination, electrophilic chlorination and sulfide oxidation

Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy.

International audienceBACKGROUND: Antibodies against M-type phospholipase A2 receptor (PLA2R) are serological markers of disease activity in patients with idiopathic membranous nephropathy (iMN). To determine the most sensitive test for the diagnosis of PLA2R-related membranous nephropathy (MN) irrespective of sampling time, we investigated the presence of PLA2R in glomerular immune deposits and assessed circulating anti-PLA2R antibodies in a retrospective cohort of Czech patients with idiopathic, lupus and other few secondary MN. METHODS: We tested archival paraffin-embedded kidney biopsies of 84 consecutive patients with biopsy-proven MN, for the presence of PLA2R in glomerular immune deposits and we measured circulating anti-PLA2R antibodies using the indirect immunofluorescence test, all reagents being commercially available. RESULTS: In 45 of 65 (69%) patients with iMN, PLA2R was detected in a finely granular pattern in sub-epithelial deposits along glomerular capillary loops. Circulating anti-PLA2R antibodies were detected in 20 of 31 (65%) sera from patients sampled during active disease. Six patients with active disease were negative for circulating anti-PLA2R antibodies despite PLA2R antigen positivity in the kidney biopsies. Only 8 of 37 (22%) sera sampled at the time of remission were PLA2R positive while PLA2R antigen was found in 22 of the 37 (59%) corresponding biopsies. PLA2R was found in immune deposits in 3 patients with secondary MN (2 with hepatitis B, and 1 with sarcoidosis) but in none of the 16 patients with lupus. CONCLUSIONS: In case of delayed serum sampling, assessment of PLA2R antigen in biopsy specimens is more sensitive than the serological test for the diagnosis of PLA2R-related MN which can be established retrospectively

Comments on the geology of the Crimean Peninsula and a reply to a recent publication on the Theodosia area by Arkadiev et al. (2019): "The calcareous nannofossils and magnetostratigraphic results from the Upper Tithonian-Berriasian of Feodosiya region (Eastern Crimea)"

International audienceHere we assess the evidence for the placing of magnetic and fossil biozonal boundaries in Upper Tithonian to Lower Berriasian (Jurassic–Cretaceous boundary) sedimentary rocks on the Black Sea coast south of Theodosia (Ukraine): that is, in magnetozones M19n to M17r. We consider our earlier-published results from these sections in relation to the correlative pattern that has become well established further west in Tethys. Additionally, this is compared and contrasted with other, alternative, results from Crimea that have been published in recent times

Assessment of somaclonal variation in somatic embryo-derived plants of yacon [Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson] using inter simple sequence repeat analysis and flow cytometry

Background: Yacon (Smallanthus sonchifolius) is a root crop native to the Andean region. Low sexual reproductive capacity is a major constraint facing the genetic breeding of this crop. Biotechnological techniques offer alternative ways to widen genetic variability. We investigated somaclonal variation in regenerants of yacon derived from in vitro somatic embryogenesis using simple sequence repeat (ISSR) analysis and flow cytometry. Results: Twenty tested ISSR primers provided a total of 7848 bands in 60 in vitro regenerants and control plant. The number of bands for each primer varied from 3 to 10, and an average of 6.95 bands was obtained per ISSR primer. Eight primers were polymorphic and generated 10 polymorphic bands with 7.19% mean polymorphism. ISSR analysis revealed genetic variability in 6 plants under study. These regenerants had Jaccard's distances 0.104, 0.020, 0.040, 0.106, 0.163 and 0.040. Flow cytometric analysis did not reveal changes of relative nuclear DNA content in regenerants suggesting that the plants obtained via somatic embryogenesis had maintained stable octoploid levels. Conclusions: Our findings show that indirect somatic embryogenesis could be used in yacon improvement to widen genetic variability, especially when low sexual reproductive capacity hinders classical ways of breeding