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Chronic hepatitis C (CHC) is a leading cause of liver disease. Despite the improved efficacy of new antivirals, their high costs preclude their adoption in resource-limited settings, where CHC prevalence is highest. We developed a triplex high-resolution melting assay for the simultaneous assessment of three genetic polymorphisms related to the response to treatment and development of advanced fibrosis in CHC: IFNL3 rs12979860, ABCB11 rs2287622, and RNF7 rs16851720. We validated the assay in clinical samples from 130 CHC patients treated with classic therapy. The assay showed excellent reproducibility and 100% accuracy, sensitivity, and specificity against the gold standard Sanger sequencing. When added to routine examination data, genotype information significantly improved their performance for prediction of advanced liver fibrosis and sustained virological response (P = 0.041 and P= 0.011, respectively). Correspondingly, the full models had area under the receiver operating characteristic curve values of 0.842 (95% CI, 0.773–0.911) and 0.921 (95% CI, 0.870–0.972) and integrated discrimination improvements of 7.5% (95% CI, 2.5%–12.5%; P = 0.003) and 11.5% (95% CI, 5.8%–17.2%; P < 0.001), respectively. This is the first report on a diagnostic test for simultaneous genotyping of IFNL3, ABCB11, and RNF7in CHC patients. Reliable and inexpensive, the assay should provide useful information for the clinical management of CHC, like identification of patients at risk of rapid disease progression or with high chances of response to classic therapy.

This paper analyses the evolution of exports’ value and sophistication during 2004-2012, using Hausmann, Hwang & Rodrik (2007) methodology. Focusing on Central and Eastern Europe, it is underlined that these states have to intensify efforts to support innovation-led growth through higher investments into technology intensive and sophisticated sectors. Export performance indicators are heterogeneous across countries, but also within the same country. We use panel fixed-effects models in order to investigate regional disparities of external results at county level in the case of Romania. The empirical results show that counties’ trade volumes and sophistication are explained by region specific factors (value added and foreign direct investment) and, more importantly, by micro-level behaviour. Based on Total Factor Productivity, computed by Wooldridge (2009)GMM method, we find that heterogeneity of firm-level technology and efficiency is the key for explaining the differences in aggregate trade outcomes. The performance of high percentiles firms drives external results: more sophisticated and higher volumes of exports are recorded in regions where the productivity distributions have fatter right tails. This evidence brings into question the efficiency of policy measures targeting external competitiveness, highlighting the importance of taking into account the entire firm-level performance distributions, rather than just the average.

ABSTRACTData on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.)

Nucleophilic aromatic substitution of all the chlorine ­atoms in 1,3,5,7,9-pentachlorocorannulene and in decachloro­corannulene by sodium alkanethiolates gives 1,3,5,7,9-pentakis(1-alkylthio)corannulenes, C20H5(SR)5, and decakis(1-alkylthio)cor­annulenes, C20(SR)10, respectively, with arms of varying lengths attached around the perimeter (R = n-propyl, n-hexyl, and n-dodecyl). The corresponding reaction of decachlorocorannulene with ortho-C6H4(SNa)2 gives pentakis(1,4-benzodithiino)corannulene, a molecular bowl with 6 Å flaps on all five sides. Such compounds represent attractive candidates for the formation of discotic liquid crystals and/or supramolecular complexes with fullerenes and other convex guests.

The molecular structure of decachlorocorannulene has been investigated by gas-phase electron diffraction with help from quantum chemical calculations at the HF and B3LYP level with several basis sets and from normal coordinate analysis. The structure is in excellent agreement with the prediction from the B3LYP/ 6-311G* calculation. The molecule of C5v symmetry is bowl-shaped with five six-membered rings fused to the central five-membered ring and to each other. The bowl is flatter than the similar corannulene molecule and is consistent with the lower inversion barrier predicted from calculations. The bond lengths (rg/Å) with uncertainties of 2σ for the four different types of C−C bonds are C1−C2 (in the C5 ring, or “hub”) = 1.421(17), C1−C6 (spokes from the hub) = 1.383(23), C6−C7 (flanking bonds from ends of spokes) =1.472(18), and C7−C8 (the rim bonds) = 1.410(27). The C−Cl bond length is 1.732(5) Å.

Eine Reduktionskaskade: Die Reduktion von Indenocorannulen durch Kalium führt zur Bildung der diastereomeren Dimere 1und/oder 2; dies ist die erste reduktive Dimerisierung eines großen, nichtplanaren polycyclischen aromatischen Kohlenwasserstoffs. Die zweifache Bildung dieser Dimere und ihre Dissoziation zu den monomeren Spezies wurde NMR‐spektroskopisch verfolgt.

A reduction cascade: The reduction of indenocorannulene by potassium leads to the formation of the diastereomeric dimers 1and/or 2; this is the first case of reductive dimerization of a large nonplanar polycyclic aromatic hydrocarbon. The twofold formation of these dimers, and their dissociation to the monomeric species, was monitored by NMR spectroscopic methods.

The regulation of human natural killer (NK) activity by IgG described previously by us depends on the ability of cytophilic molecules of monomeric IgG (mIgG) to inhibit the subsequent killing of NK-sensitive targets. Highly purified NK cells obtained from human peripheral blood are able to directly bind mIgG as well as antigen-complexed IgG through its Fc region. The demonstration that NK cells bear labile cytophilic IgG, a property which usually has been attributed to L cells, indicates that mIgG-induced inhibition of NK activity is mediated by direct interactions between the inhibitory ligand and cytotoxic effector cells. The Fc receptor (FcR) mediating downregulation of NK cytotoxicity appeared to be FcRγIII, previously found to be selectively expressed on NK cells and granulocytes. In studies of unidirectional cross-inhibition of mIgG binding to NK cells by various anti-CD16 monoclonal antibodies, binding characteristics of mIgG or complexed IgG were similar. Thus, the FcRγIII for mIgG appear to be indistinguishable from receptors responsible for binding of polymeric IgG on human NK cells. The negative regulation of NK activity by mIgG was not attributable to inhibition of conjugate formation between effector cells and K532 targets, but rather to inhibition of a post-binding event involved in killing of conjugated targets. The data presented suggest that the Fcγ RIII on human NK cells can either mediate killing against IgG antibody-coated target cells or, upon interaction with cytophilic monomeric ligand in soluble form, induce inhibition of NK activity. Copyright 1993, 1999 Academic Press