Obtaining a rapid deflagration-to-detonation transition (DDT) within a short smooth tube is a challenging task. Here, an unconventional means of flame acceleration propagating upstream in subsonic and supersonic mixtures within a smooth tube was introduced to acquire a speedy DDT. The Navier–Stokes equations with an adaptive mesh refinement technique and a detailed hydrogen–air chemistry reaction mechanism of 11 species and 27 steps were utilized to resolve the entire DDT characteristics. The effect of the initial Mach number on flame acceleration and DDT mechanism was revealed comprehensively. The results demonstrated that a prompt oblique shock wave (SW) occurs when the flame propagates upstream along the boundary walls due to the boundary layer influence. An intense coupling between the SW and the leading flame front is enhanced by increasing the initial Mach number of the mixture. The speedy generation of the oblique SW is formed at the incipient stage, mainly produced by the boundary layer influence and the coalescences of the compression waves. Consequently, the run-up time to detonation is shortened accordingly through a fierce reflected SW due to the intense leading SW after it reflects from the confined wall. Furthermore, three kinds of DDT evolution are revealed from the obtained results: (1) localized ignition in the upper boundary wall after the reflected and transverse shock waves propagate in the upper wall regions; (2) autoignition is formed in the confined wall corner after the reflected SW; and (3) direct detonation transition occurs at the end wall behind a strongly reflected SW in the supersonic case.
The relationship between topographical and non-topographical cognitive measures was studied for 25 elderly participants. The topographical measures were the Camden Topographical Recognition Memory Test (CTRMT), a Topographical Mental Rotation Test (TMRT), and a Virtual Pond Maze (VPM). The non-topographical tests were the Montreal Cognitive Assessment (MoCA), the Trail-Making Test-B (TMT-B), and a matching-to-sample Visual Short-Term Memory Test (VSMT). Only the correlation (0.48) between the TMT-B and the TMRT attained significance; the bivariate correlations among the three topographical measures were modest, ranging from 29 to 33, although they did correlate highly with a topographic composite score (0.69-0.78). A factor analysis yielded a further distinction between the topographical and non-topographical measures. Loadings for the three topographical measures on a presumed “topographical” factor ranged from 0.62 to 0.71 but only from 0.17 to 0.23 for the second factor. The MoCA and TMT-B loaded on both factors, while the VSMT measure loaded poorly (-0.03) on the topographical factor but highly (0.89) on the second factor. The results suggest that standard measures of cognitive function may not be optimal for specific assessment of topographical abilities, the best predictor of impending Alzheimer’s dementia.
Purpose: CXCR4 has been identified as a prognostic marker for acute myeloid leukemia (AML) and other malignancies. We describe the development and characterization of a fully human antibody to CXCR4 and its application for therapy of AML, non–Hodgkin lymphoma (NHL), chronic lymphoid leukemia (CLL), and multiple myeloma. Experimental Design: Human transgenic mice were immunized with CXCR4-expressing cells, and antibodies reactive with CXCR4 were analyzed for apoptosis induction and ability to interfere with CXCL12-induced migration and calcium flux. In vivo efficacy was determined in multiple AML, NHL, and multiple myeloma xenograft tumors in severe combined immunodeficient mice. Results: BMS-936564/MDX-1338 is a fully human IgG4 monoclonal antibody that specifically recognizes human CXCR4. In vitro studies show that MDX-1338 binds to CXCR4-expressing cells with low nanomolar affinity, blocks CXCL12 binding to CXCR4-expressing cells, and inhibits CXCL12-induced migration and calcium flux with low nanomolar EC50 values. When given as monotherapy, MDX-1338 exhibits antitumor activity in established tumors including AML, NHL, and multiple myeloma xenograft models. In addition, we show that MDX-1338 induced apoptosis on a panel of cell lines and propose that antibody-induced apoptosis is one of the mechanisms of tumor growth inhibition. Conclusions: BMS-936564/MDX-1338 is a potent CXCR4 antagonist which is efficacious as monotherapy in tumor-bearing mice and is currently in phase I for the treatment of relapsed/refractory AML, NHL, CLL, and multiple myeloma. Clin Cancer Res; 19(2); 357–66. ©2012 AACR.
Objective. The aim was to determine the ability of several thin-film polymer formulations, with and without incorporated antifungals, to inhibit Candida albicans biofilm growth on denture material. The inhibition of C. albicans biofilms on maxillary dentures could play a significant role in preventing the development of denture stomatitis.Study design. Low-porosity and high-porosity thin-film polymer formulations were used and one of the following fungicides was added: 1) chlorhexidine diacetate at 1.0%; 2) nystatin at 1.0%; or 3) amphotericin B at 0.1%. These coatings were placed on rectangular (12 x 10 mm) dental resin material samples. A subset of the coated dental materials were brushed to simulate denture cleaning for 1 minute per day for 1 year. Candida albicans biofilms were formed on polymethylmethacrylate (PMMA) specimens placed in 24-well polystyrene plates, and the extent of biofilm formation on coated and noncoated specimens was assessed using a 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay.Results. Thin-film polymer PMMA coatings alone, without an antifungal agent, produced a small significant reduction in C. albicans biofilm formation compared with control PMMA. However, incorporation of antifungal medications into the thin-film polymer reduced biofilm formation between 70% and 80% with nystatin, and between 50% and 60% with amphotericin B. Biofilm reduction with chlorhexidine (up to 98%) was significantly greater than all other formulations tested (P < .025).Conclusion. This novel thin-film coating with various antifungals effectively inhibits C. albicans biofilm formation and should be evaluated as a potential preventive therapy for denture stomatitis. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:669-672)
