A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent. (c) 2011 Wiley Periodicals, Inc.

On the contributions of different micromechanisms for enhancement in the strength of TI-6Al-4V alloy upon B addition: A nanomechanical analysis

The addition of small amount of boron to Ti and it alloys refines the as-cast microstructure and enhances the mechanical properties. In this paper, we employ nanoindentation on each of the constituent phases in the microstructure and `rule-of-mixture' type analysis to examine their relative contributions to the strength enhancement in a Ti-6Al-4V alloy modified with 0.3 wt% B. Our results indicate to two main contributors to the relatively higher flow strength of B-modified alloy vis-a-vis the base alloy: (a) strengthening of alpha phase due to the reduction in the effective slip length that occurs as a result of the microstructural refinement that occurs upon B addition, and (b) composite strengthening caused by the TiB whiskers present in the alloy. (C) 2015 Elsevier B.V. All rights reserved.

Roles for Transcription Factors Sp1, NF-kappa B, IRF3, and IRF7 in Expression of the Human IFNL4 Gene

The expression of a biologically active human IFN4 depends on the presence of a frameshift deletion polymorphism within the first exon of the interferon lambda 4 (IFNL4) gene. In this report, we use the lung carcinoma-derived cell line, A549, which is genetically viable to express a functional IFN4, to address transcriptional requirements of the IFNL4 gene. We show that the GC-rich DNA-binding transcription factor (TF) specificity protein 1 (Sp1) is recruited to the IFNL4 promoter and has a role in induction of gene expression upon stimulation with viral RNA mimic poly(I:C). By using RNAi and overexpression strategies, we also show key roles in IFNL4 gene expression for the virus-inducible TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), IFN regulatory factor 3 (IRF3), and IRF7. Interestingly, we also observe that overexpression of IFN4 influences IFNL4 promoter activity, which may further be dependent on the retinoic acid-inducible gene-I (RIG-I)-like receptor pathway. Together, our work for the first time reports on the functional characterization of the human IFNL4 promoter.

Stable p-type conductivity in B and N co-doped ZnO epitaxial thin film

We report on the observation of stable p-type conductivity in B and N co-doped epitaxial ZnO thin films grown by pulsed laser deposition. Films grown at higher oxygen partial pressure (similar to 10(-1) Torr) shows p-type conductivity with a carrier concentration of similar to 3 x 10(16) cm(-3). This p-type conductivity is associated with the significant decrease in defect emission peaks due to the vacancy oxygen (V-O) and Schottky type-I native defects compared to films grown at low oxygen partial pressure (similar to 10(-5) Torr). The p-type conductivity is explained with the help of density functional theory (DFT) calculation considering off-stoichiometric BN1+x in the ZnO lattice. (C) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim