3-Phenyl-2-(piperidin-1-yl)-3,5,6,8-tetra­hydro-4H-thio­pyrano[3′,4′:2,3]thieno[5,4-d]pyrimidin-4-one

In the title compound, C20H21N3OS2, the piperidinyl ring has a distorted chair conformation. Weak inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers. The crystal packing exhibits short inter­molecular S⋯S distances of 3.590 (2) Å

Dynamic response of underground box-type structure to explosion seismic waves

The dynamic response of lined tunnels with a uniform box-type cross-section buried into elastic half-space to explosion seismic waves is studied by employing the matrix force method and treating the structure as a connecting rod system interacting with foundation. The main equations for dynamic analyzing of the hyperstatic structure are deduced and solving method is proposed. A case study is implemented to investigate the influence of span-height ratio of the structure and foundation-structure wave impedance ratio. The results are presented in nondimensional form to obtain a clear physical understanding of the dynamic response of structure. It is shown that the dynamic response of box-type structure can be significantly influenced by the span-height ratio as well as the foundation conditions. Since nondimensional parameters are adopted, the results are independent of dimension and can extend to structures with different size and working conditions. This study provides an analysis method and new insights into the dynamic response of underground box-type structures

A Coaxial Cable Fabry-Perot Interferometer for Sensing Applications

This paper reports a novel coaxial cable Fabry-Perot interferometer for sensing applications. The sensor is fabricated by drilling two holes half-way into a coaxial cable. The device physics was described. The temperature and strain responses of the sensor were tested. The measurement error was calculated and analyzed

Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress

<p>Abstract</p> <p>Background</p> <p>Classical swine fever (CSF) caused by virulent strains of Classical swine fever virus (CSFV) is a haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopoenia and immunosuppression, and the swine endothelial vascular cell is one of the CSFV target cells. In this report, we investigated the previously unknown subcellular localization and function of CSFV NS2 protein by examining its effects on cell growth and cell cycle progression.</p> <p>Results</p> <p>Stable swine umbilical vein endothelial cell line (SUVEC) expressing CSFV NS2 were established and showed that the protein localized to the endoplasmic reticulum (ER). Cellular analysis revealed that replication of NS2-expressing cell lines was inhibited by 20-30% due to cell cycle arrest at S-phase. The NS2 protein also induced ER stress and activated the nuclear transcription factor kappa B (NF-κB). A significant increase in cyclin A transcriptional levels was observed in NS2-expressing cells but was accompanied by a concomitant increase in the proteasomal degradation of cyclin A protein. Therefore, the induction of cell cycle arrest at S-phase by CSFV NS2 protein is associated with increased turnover of cyclin A protein rather than the down-regulation of cyclin A transcription.</p> <p>Conclusions</p> <p>All the data suggest that CSFV NS2 protein modulate the cellular growth and cell cycle progression through inducing the S-phase arrest and provide a cellular environment that is advantageous for viral replication. These findings provide novel information on the function of the poorly characterized CSFV NS2 protein.</p

Thermokinetic profile of NDM-1 and its inhibition by small carboxylic acids

The New Delhi metallo-β-lactamase (NDM-1) is an important clinical target for antimicrobial research, but there are insufficient clinically useful inhibitors and the details of NDM-1 enzyme catalysis remain unclear. The aim of this work is to provide a thermodynamic profile of NDM-1 catalysed hydrolysis of β-lactams using an isothermal titration calorimetry (ITC) approach and to apply this new method to the identification of new low-molecular-weight dicarboxylic acid inhibitors. The results reveal that hydrolysis of penicillin G and imipenem by NDM-1 share the same thermodynamic features with a significant intrinsic enthalpy change and the release of one proton into solution, while NDM-1 hydrolysis of cefazolin exhibits a different mechanism with a smaller enthalpy change and the release of two protons. The inhibitory constants of four carboxylic acids are found to be in the micromolar range. The compounds pyridine-2,6-dicarboxylic acid and thiazolidine-2,4-dicarboxylic acid show the best inhibitory potency and are confirmed to inhibit NDM-1 using a clinical strain of Escherichia coli. The pyridine compound is further shown to restore the susceptibility of this E. coli strain to imipenem, at an inhibitor concentration of 400 μM, while the thiazoline compound also shows a synergistic effect with imipenem. These results provide valuable information to enrich current understanding on the catalytic mechanism of NDM-1 and to aid the future optimisation of β-lactamase inhibitors based on these scaffolds to tackle the problem of antibiotic resistance