Identification of yeast DNA topoisomerase II mutants resistant to the antitumor drug doxorubicin: implications for the mechanisms of doxorubicin action and cytotoxicity

Doxorubicin is a therapeutically useful anticancer drug that exerts multiple biological effects. Its antitumor and cardiotoxic properties have been ascribed to anthracycline-mediated free radical damage to DNA and membranes. Evidence for this idea comes in part from the selection by doxorubicin from stationary phase yeast cells of mutants (petites) deficient in mitochondrial respiration and therefore defective in free radical generation. However, doxorubicin also binds to DNA topoisomerase II, converting the enzyme into a DNA damaging agent through the trapping of a covalent enzyme-DNA complex termed the 'cleavable complex.' We have used yeast to determine whether stabilization of cleavable complexes plays a role in doxorubicin action and cytotoxicity. A plasmid-borne yeast TOP2 gene was mutagenized with hydroxylamine and used to transform drug-permeable yeast strain JN394t2-4, which carries a temperature-sensitive top2-4 mutation in its chromosomal TOP2 gene. Selection in growth medium at the nonpermissive temperature of 35 degrees in the presence of doxorubicin resulted in the isolation of plasmid-borne top2 mutants specifying functional doxorubicin-resistant DNA topoisomerase II. Single-point changes of Gly748 to Glu or Ala642 to Ser in yeast topoisomerase II, which lie in and adjacent to the CAP-like DNA binding domain, respectively, were identified as responsible for resistance to doxorubicin, implicating these regions in drug action. None of the mutants selected in JN394t2-4, which has a rad52 defect in double-strand DNA break repair, was respiration-deficient. We conclude that topoisomerase II is an intracellular target for doxorubicin and that the genetic background and/or cell proliferation status can determine the relative importance of topoisomerase II- versus free radical-killing.     

A spin wave resonance study on reentrant Au77Fe23 films

Thin films prepared by both flash and slow evaporation of the bulk Au₇₇Fe₂₃ alloy have been studied by electron spin resonance (ESR) technique at the temperature range between 77–300 K. A series of spin wave resonance (SWR) peaks were observed at all temperatures when the external de magnetic field is applied along the directions lying in a small angular interval with respect to the film normal. The classical spin wave model has been used to analyze the experimental data. The magnetic parameters, such as exchange stiffness constant, the effective bulk and the surface anisotropy energy parameters of the system have been derived as a function of temperature. While the easy plane surface anisotropy almost remains constant, considerable increments were found in the exchange parameter, the magnetization and the linewidth with decreasing temperature. The SWR linewidths for the films obtained by slow evaporation at higher substrate temperatures are noticeably smaller compared to those of the film prepared by flash evaporation technique.     

Effect of primaquine on the elimination of sexual forms of Plasmodium falciparum in vivo]

A study was made on 49 patients, carriers of sexual forms of Plasmodium falciparum, verified through thick smear tests, who received 45 and 90 mg of primaquine base in different schedules selected at random. None of the employed schedules proved better than the traditional one of 45 mg base in a unique dose, although the schedule of 45 mg on the first and third days showed a slight reduction of the time of elimination of the parasitemia. Thus, further studies are recommended. No other factors showed an influence on the time of elimination of the parasitemia.     

Flexural strength–ductility performance of flanged beam sections cast of high‐strength concrete

Flanged sections are often used for long‐span concrete beams to maximize their structural efficiency. However, although for the same sectional area a flanged section could render a higher flexural strength, it would also lead to a lower flexural ductility, especially when heavily reinforced. Thus, when evaluating the flexural performance of a beam section, both the flexural strength and ductility need to be considered. In this study, the post‐peak flexural behaviour of flanged sections is evaluated by means of an analytical method that uses the actual stress–strain curves of the materials and takes into account strain reversal of the tension reinforcement. From the numerical results, the flexural strength–ductility performance of flanged sections is investigated by plotting the strength and ductility that could be simultaneously achieved in the form of design graphs. It is found that (1) at the same overall dimensions and with the same amount of reinforcement provided, a flanged section has lower flexural ductility than a rectangular section; (2) at the same overall dimensions, a flanged section has inferior strength–ductility performance compared to a rectangular section; and (3) at the same sectional area, a flanged section has better strength–ductility performance compared to a rectangular section. Copyright © 2003 John Wiley & Sons, Ltd.     

Effects of minor Cu and Si additions on glass forming ability and mechanical properties of Co-Fe-Ta-B Bulk metallic glass

Effect of Cu and Si substitutions for Co and B on the glass forming ability (GFA) of Co_(43-x)Cu_xFe₂₀Ta_5.5B_(31.5-x)Si_y (x=0-1.5 and y=5-10) were systematically investigated by X-ray diffraction, optical microscopy, scanning electron microscopy, and differential scanning calorimetry. In order to evaluate the contribution of copper and silicon, appropriate amounts of copper and silicon were individually introduced to the base alloy composition. By using the effects of copper and silicon together, significant enhancement was obtained and the critical casting thickness (CCT) of the base alloy was increased three times from 2 mm to 6 mm. Moreover, mechanical properties of the alloys were examined by compression tests and Vickers hardness measurements. The compression test results revealed that the glassy alloys having enhanced GFA shows high strength of about 3500-4000 MPa. In addition, existence of (Co,Fe)₂B and (Co,Fe)_20.82Ta_2.18B₆ crystalline phases in glassy matrix influences the hardnesses of the alloys compared to monolitic glassy structure having hardness of about 1200 Hv.     

平板封头与筒体连接区的疲劳分析

采用有限元分析软件ANSYS,对平板封头与筒体连接区进行有限元分析,并基于计算结果对该连接区进行疲劳分析,使机械设备疲劳计算更精确更经济。     

Comparison of adaptive neuro‐fuzzy inference system and artificial neural networks for estimation of oxidation parameters of sunflower oil added with some natural byproduct extracts

BACKROUND: Apple pomace, orange peel and potato peel, which have important antioxidative compounds in their structures, are byproducts obtained from fruit or vegetable processing. Use of vegetable extracts is popular and a common technique in the preservation of vegetable oils. Utilization of apple pomace, orange peel and potato peel extracts as natural antioxidant agents in refined sunflower oil during storage in order to reduce or retard oxidation was investigated. All byproduct extracts were added at 3000 ppm to sunflower oil and different nonlinear models were constructed for the estimation of oxidation parameters. RESULTS: Peroxide values of sunflower oil samples containing different natural extracts were found to be lower compared to control sample. Adaptive neuro‐fuzzy inference system (ANFIS) and artificial neural networks (ANN) were used for the construction of models that could predict the oxidation parameters and were compared to multiple linear regression (MLR) for the determination of the best model with high accuracy. It was shown that the ANFIS model with high coefficient of determination (R² = 0.999) performed better compared to ANN (R² = 0.899) and MLR (R² = 0.636) for the prediction of oxidation parameters CONCLUSION: Incorporation of different natural byproduct extracts into sunflower oil provided an important retardation in oxidation during storage. Effective predictive models were constructed for the estimation of oxidation parameters using ANFIS and ANN modeling techniques. These models can be used to predict oxidative parameter values. Copyright © 2011 Society of Chemical Industry     

活性炭工艺去除水中典型药品的效能与机理

药品和个人护理品（PPCPs）因其潜在的环境和健康风险受到了广泛关注。实验选取8种典型药品为对象,采用中试规模的活性炭工艺研究了其去除效果和影响因素。结果表明,活性炭工艺对安替比林、达舒平、舒必利、磺胺甲口恶唑、泰妙菌素和氧苄胺嘧啶等的去除率为50%～90%,对林肯霉素和氨糖美辛的去除率均小于35%。典型药品的去除率受到滤速、有机物和pH等因素的影响,其中,氨糖美辛、林肯霉素和泰妙菌素等的去除率受滤速影响较大;磺胺甲口恶唑的去除率受pH影响较大。有机物对典型药品去除率的影响既有促进作用,又有抑制作用。典型药品的物化性质对其去除行为有重要影响,这有利于从分子水平上认识活性炭工艺对典型药品的去除机理。     

A mini review on chemical fixation of CO 2 : Absorption and catalytic conversion into cyclic carbonates

In this article, we present our research results on chemical fixation of CO₂ using organobismuth compounds. We fabricated bismuth biphenoate complex, Zn-Mg-Al composite oxides, and SBA-15 or Al-SBA-15 immobilized hydroxyl ionic liquid for CO₂ cycloaddition onto epoxides. The hypervalent bismuth compounds show good ability for association and dissociation with CO₂. The bismuth biphenolate complexes are catalytically effective for the cycloaddition reaction. The heterogeneous catalysts, viz. Zn-Mg-Al oxides and SBA-15 or Al-SBA-15 immobilized ionic liquid, are efficient for the synthesis of cyclic carbonate from CO₂ and epoxide. It is found that the presence of a trace amount of water can improve the catalytic activity of the immobilized ionic liquid.