Robustness of Equations Under Operational Extensions

Sound behavioral equations on open terms may become unsound after conservative extensions of the underlying operational semantics. Providing criteria under which such equations are preserved is extremely useful; in particular, it can avoid the need to repeat proofs when extending the specified language. This paper investigates preservation of sound equations for several notions of bisimilarity on open terms: closed-instance (ci-)bisimilarity and formal-hypothesis (fh-)bisimilarity, both due to Robert de Simone, and hypothesis-preserving (hp-)bisimilarity, due to Arend Rensink. For both fh-bisimilarity and hp-bisimilarity, we prove that arbitrary sound equations on open terms are preserved by all disjoint extensions which do not add labels. We also define slight variations of fh- and hp-bisimilarity such that all sound equations are preserved by arbitrary disjoint extensions. Finally, we give two sets of syntactic criteria (on equations, resp. operational extensions) and prove each of them to be sufficient for preserving ci-bisimilarity.Comment: In Proceedings EXPRESS'10, arXiv:1011.601

Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis

Introduction We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). Methods mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant. Results SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro. Conclusions Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthriti

Efficacy and safety of a single-dose mebendazole 500 mg chewable, rapidly-disintegrating tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment in pediatric patients : a double-blind, randomized, placebo-controlled, phase 3 study

This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1-15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 +/- 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: -5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: -16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified

BriX: a database of protein building blocks for structural analysis, modeling and design

High-resolution structures of proteins remain the most valuable source for understanding their function in the cell and provide leads for drug design. Since the availability of sufficient protein structures to tackle complex problems such as modeling backbone moves or docking remains a problem, alternative approaches using small, recurrent protein fragments have been employed. Here we present two databases that provide a vast resource for implementing such fragment-based strategies. The BriX database contains fragments from over 7000 non-homologous proteins from the Astral collection, segmented in lengths from 4 to 14 residues and clustered according to structural similarity, summing up to a content of 2 million fragments per length. To overcome the lack of loops classified in BriX, we constructed the Loop BriX database of non-regular structure elements, clustered according to end-to-end distance between the regular residues flanking the loop. Both databases are available online (http://brix.crg.es) and can be accessed through a user-friendly web-interface. For high-throughput queries a web-based API is provided, as well as full database downloads. In addition, two exciting applications are provided as online services: (i) user-submitted structures can be covered on the fly with BriX classes, representing putative structural variation throughout the protein and (ii) gaps or low-confidence regions in these structures can be bridged with matching fragments