VX-680 is a potent inhibitor of Aurora kinases that induces the accumulation of cells with > or =4N DNA content, followed by cell death. Here, we define the role of p53 and p21(Waf1/Cip1) in cell cycle perturbations following exposure to VX-680. Endoreduplication and apoptosis in response to VX-680 are limited in A549 and MCF-7 cells expressing wild-type p53, and markedly enhanced in cells lack...

Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis (CF). A potential CF therapy would be to repair CFTR processing mutants. It has been demonstrated that processing mutants of P-glycoprotein (P-gp), CFTR's sister protein, can be efficiently repaired by a drug-rescue mechanism. Many arginine suppressors that mimic drug-rescue have been identif...

Our previous study showed that stimulation of adenosine A(1) receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and beta-adrenergic vasodilation versus vasoconstriction mediated by neural and unknown humoral factors. In the present study we investigated the relative contribution of three major po...

Two promising uncharged reactivators for inhibited human BChE and AChE have been described. These compounds show an ability to reactivate VX-inhibited BChE largely superior to those of known pyridinium aldoximes. Moreover, these oximes also exhibit a good ability to reactivate VX-, tabun- and paraoxon-inhibited human AChE.

We present a high-resolution (2.0 A) crystal structure of the catalytic domain of a mutant form of the Abl tyrosine kinase (H396P; Abl-1a numbering) that is resistant to the Abl inhibitor imatinib. The structure is determined in complex with the small-molecule inhibitor VX-680 (Vertex Pharmaceuticals, Cambridge, MA), which blocks the activity of various imatinib-resistant mutant forms of Abl, i...

Photometric observations of the double-mode pulsator VX Hya are presented. They analyzed with a stroboscopic method, completed by Fourier analysis.

The experimental measurement and modeling of liquid chemical agent spread and sorption on a porous substrate are described. Experimental results with the nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) demonstrate that the wetted imprint volume increases, even after the sessile drop volume is exhausted. This indicates the wetted imprint is only partially saturated, ...

We discuss relationships in Lindelöf spaces among the properties “Menger”, “Hurewicz”, “Alster”, “productive”, and “D”. This note is a continuation of [13]. The question of what additional assumptions ensure that the product of two Lindelöf spaces is Lindelöf is natural and well-studied. See e.g., [28], [30], [2], [3], [4], [5], [6], [32], [33]. D-spaces were introduced in [20]. Definition. A s...

Molecular Structure and Function, Peter Gilgan Center for Research and Learning, Hospital for Sick Children (R.P.H, J.E.D., P.A.C., J.F.-K.) and Department of Biochemistry, University of Toronto (J.F.-K.), Toronto, ON, Canada; Center for Structural Biology (Z.Y., C.G.B.) and Department of Chemistry (C.G.B.), University of Alabama at Birmingham, Birmingham, AL, USA; Department of Physiology at U...