Davis-Beirut reaction: route to thiazolo-, thiazino-, and thiazepino-2H-indazoles.

Methods for the construction of thiazolo-, thiazino-, and thiazepino-2H-indazoles from o-nitrobenzaldehydes or o-nitrobenzyl bromides and S-trityl-protected 1°-aminothioalkanes are reported. The process consists of formation of the requisite N-(2-nitrobenzyl)(tritylthio)alkylamine, subsequent deprotection of the trityl moiety with TFA, and immediate treatment with aq. KOH in methanol under Davis-Beirut reaction conditions to deliver the target thiazolo-, thiazino-, or thiazepino-2H-indazole in good overall yield. Subsequent S-oxidation gives the corresponding sulfone

ANALISIS HUBUNGAN PRICE COST MARGIN DAN MARKET SHARE DALAM KERANGKA STRUCTURE CONDUCT PERFORMANCE (SCP) : STUDI KASUS PADA INDUSTRI PADAT MODAL DI INDONESIA

This study aims to analyze the relationship between Price Cost Margin (PCM) and Market Share (MS) in the framework of structure-conduct-performance (SCP) paradigm. This research is conducted at firm level in medium and large manufacturing industry with capital-intensive character. The capital-intensive industry has made an important contribution in the process of industrialization in Indonesia, until the manufacturing industry becomes the largest contributor to GDP. One measure of company performance is profitability. In the SCP framework, the profitability level is influenced by either structure or behaviour of industry, whether in linear or reciprocal relationship. In SCP size, the level of profit both by structure and industry behavior, both in the structure of linear or reciprocal relationships. This study uses simultaneous equation model with two stage least square estimation (TSLS) method and this research also uses the panel data structure in seven capital-intensive industries from 2010 to 2014. In this research there are two equations which make PCM and MS as endogenous variables. The results are appropriate with the hypothesis, except for the relation between PCM and MS, which found to be negative. Other results indicate that MES has a positive effect on PCM. Intensity of capital to output (KO) have positive effect to PCM, and firm growth (GROWTH) have positive effect to PCM. In the second equation, PCM has negative effect on MS, while MES, KO and SIZE have positive and significant effect to MS. MES as barrier to entry variable, while KO and SIZE are performance and structure variables that also influence M

Jerry's judges and the politics of the death penalty: The judicial election of 1986

Includes bibliographical references (leaves 73-78)On February 12, 1977, California Governor Jerry Brown nominated Rose Elizabeth Bird as chief justice ofthe California Supreme Court, making her the first female member of the court. Throughout her tenure on the Court, Bird faced criticism over her stance on important economic and social issues facing the state such as Proposition 13 and the death penalty. Throughout the 1970s and 1980s numerous California politicians campaigned on law-and-order and anti-tax issues, and accusations of pro-defendant and anti-Proposition 13 rulings became the latest and most popular criticism of the Court by those such as Howard Jarvis and Attorney General George Deukmejian who would work hard to remove her and her liberal colleagues from the California Supreme Court. While the Court faced criticism over many of its death penalty rulings, the death penalty in general was in a state of flux across the nation after the United States Supreme Court ruled it to be cruel and unusual punishment in violation of the Constitution. In the 1982 gubernatorial election, Attorney General George Deukmejian criticized his opponent, Los Angeles Mayor Tom Bradley, for failing to take a position on Bird, and made the sort of people he would appoint to the bench an important issue in his campaign for governor. Four years later, in the run up to the 1986 gubematorial election, Howard Jarvis led efforts as co-chair of Californians to Defeat Rose Bird, an anti-crime and victims' rights group, to remove Chief Justice Bird, Cruz Reynoso and Joseph R. Grodin from the Court. While Chief Justice Bird was faced with insurmountable odds of a reelection victmy, Govemor George Deukmejian could relish his position to appoint a new chief justice and two associate justices and change the ideological makeup of the Califomia Supreme Court. An often overlooked chapter of the New Right movement, the reconfirmation battle of Bird and her colleagues brought upon crucial and important questions about the importance of an independent judiciary and set a dangerous precedent for future members of the Court. Furthe1more, through an analysis of this important event in Califomia history, we receive a better picture of Howard Jarvis and the New Right's impact on the state's social and economic transformation in the last decade of the twentieth century

Radiosensitization by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide under oxia and hypoxia in human colon cancer cells

BACKGROUND: The sensitizing effects of 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide (DCQ) and ionizing radiation (IR) were determined in four colon cancer cells and in FHs74Int normal intestinal cells. METHODS: Cell cycle modulation, TUNEL assay, clonogenic survival and DNA damage were examined under oxia or hypoxia. Effects on apoptotic molecules and on p-Akt and Cox-2 protein expression were investigated. RESULTS: The four cell lines responded differently to DCQ+IR; HT-29 cells were most resistant. Combination treatment caused significant increases in preG(1 )(apoptosis) in HCT-116, while G(2)/M arrest occurred in DLD-1. DCQ potentiated IR effects more so under hypoxia than oxia. Pre-exposure of DLD-1 to hypoxia induced 30% apoptosis, and G(2)/M arrest in oxia. The survival rate was 50% lower in DCQ+IR than DCQ alone and this rate further decreased under hypoxia. FHs74Int normal intestinal cells were more resistant to DCQ+IR than cancer cells.Greater ssDNA damage occurred in DLD-1 exposed to DCQ+IR under hypoxia than oxia. In oxia, p-Akt protein expression increased upon IR exposure and drug pre-treatment inhibited this increase. In contrast, in hypoxia, exposure to IR reduced p-Akt protein and DCQ restored its expression to the untreated control. Apoptosis induced in hypoxic DLD-1 cells was independent of p53-p21 modulation but was associated with an increase in Bax/Bcl-2 ratio and the inhibition of the Cox-2 protein. CONCLUSION: DCQ is a hypoxic cell radiosensitizer in DLD-1 human colon cancer cells

The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway

BACKGROUND: Although tumor hypoxia poses challenges against conventional cancer treatments, it provides a therapeutic target for hypoxia-activated drugs. Here, we studied the effect of the hypoxia-activated synthetic quinoxaline di-N-oxide DCQ against breast cancer metastasis and identified the underlying mechanisms. METHODS: The human breast cancer cell lines MCF-7 (p53 wildtype) and MDA-MB-231 (p53 mutant) were treated with DCQ under normoxia or hypoxia. Drug toxicity on non-cancerous MCF-10A breast cells was also determined. In vitro cellular responses were investigated by flow cytometry, transfection, western blotting, ELISA and migration assays. The anti-metastatic effect of DCQ was validated in the MDA-MB-231 xenograft mouse model. RESULTS: DCQ selectively induced apoptosis in both human breast cancer cells preferentially under hypoxia without affecting the viability of non-cancerous MCF-10A. Cancer cell death was associated with an increase in reactive oxygen species (ROS) independently of p53 and was inhibited by antioxidants. DCQ-induced ROS was associated with DNA damage, the downregulation of hypoxia inducible factor-1 alpha (HIF-1α), and inhibition of vascular endothelial growth factor (VEGF) secretion. In MCF-7, HIF-1α inhibition was partially via p53-activation and was accompanied by a decrease in p-mTOR protein, suggesting interference with HIF-1α translation. In MDA-MB-231, DCQ reduced HIF-1α through proteasomal-dependent degradation mechanisms. HIF-1α inhibition by DCQ blocked VEGF secretion and invasion in MCF-7 and led to the inhibition of TWIST in MDA-MB-231. Consistently, DCQ exhibited robust antitumor activity in MDA-MB-231 breast cancer mouse xenografts, enhanced animal survival, and reduced metastatic dissemination to lungs and liver. CONCLUSION: DCQ is the first hypoxia-activated drug showing anti-metastatic effects against breast cancer, suggesting its potential use for breast cancer therapy

Synthesis of YVO4:Eu3+/YBO3Heteronanostructures with Enhanced Photoluminescence Properties

Novel YVO4:Eu3+/YBO3core/shell heteronanostructures with different shell ratios (SRs) were successfully prepared by a facile two-step method. X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy were used to characterize the heteronanostructures. Photoluminescence (PL) study reveals that PL efficiency of the YVO4:Eu3+nanocrystals (cores) can be improved by the growth of YBO3nanocoatings onto the cores to form the YVO4:Eu3+/YBO3core/shell heteronanostructures. Furthermore, shell ratio plays a critical role in their PL efficiency. The heteronanostructures (SR = 1/7) exhibit the highest PL efficiency; its PL intensity of the5D0–7F2emission at 620 nm is 27% higher than that of the YVO4:Eu3+nanocrystals under the same conditions

Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice

<p>Abstract</p> <p>Background</p> <p>Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity.</p> <p>Methods</p> <p>Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ <it>in vitro</it>.</p> <p>Results</p> <p>OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression <it>in vivo</it>. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our <it>in vivo </it>findings.</p> <p>Conclusions</p> <p>Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice.</p

Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature

Santamaría-Perez, D.; Mcguire, C.; Makhluf, A.; Kavner, A.; Chulia-Jordan, R.; Jorda Moret, JL.; Rey Garcia, F.... (2016). Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature. Nature Communications. 7:1-3. doi:10.1038/ncomms13647S137Yoo, C. S. et al. Crystal structure of carbon dioxide at high pressure: “superhard” polymeric carbon dioxide. Phys. Rev. Lett. 83, 5527–5530 (1999).Santoro, M. et al. Partially collapsed cristobalite structure in the non molecular phase V in CO2 . Proc. Natl Acad. Sci. 109, 5176–5179 (2012).Datchi, F., Mallick, B., Salamat, A. & Ninet, S. Structure of polymeric carbon dioxide CO2-V. Phys. Rev. Lett. 108, 125701 (2012).Santoro, M. et al. Silicon carbonate phase formed from carbon dioxide and silica under pressure. Proc. Natl Acad. Sci. 108, 7689–7692 (2011).Santoro, M. et al. Carbon enters silica forming a cristobalite-type CO2.SiO2 solid solution. Nat. Commun. 5, 3761 (2014).Corma, A., Rey, F., Rius, J., Sabater, M. J. & Valencia, S. Supramolecular self-assembled molecules as organic directing agent for synthesis of zeolites. Nature 431, 287–290 (2004).Guth, J.-L., Kessler, H. & Wey, R. in Studies in Surface Science and Catalysis Vol. 28 (eds Murakami, Y., Iijima, A. & Ward, J. W.) 121 (Kodansha-Elsevier, 1986).Santamaria-Perez, D. et al. Exploring the chemical reactivity between carbon dioxide and three transition metals (Au, Pt, and Re) at high-pressure high-temperature conditions. Inorg. Chem. 55, 10793–10799 (2016).Magneli, A. Studies on rhenium oxides. Acta Chem. Scand. 11, 28–33 (1957)