Precursor-directed syntheses and biological evaluation of new elansolid derivatives

The antibiotic elansolid C1 (8) was isolated from Chitinophaga sancti strain FxGBF13 after fermentation in the presence of anthranilic acid. Remarkably, 8 was also obtained by addition of anthranilic acid to a crude fermentation extract containing the macrolide elansolid A2 (1*). This Michael-type conjugate addition allowed us to generate 21 new derivatives of elansolid C1 (9-29) by using various nucleophiles. Biological activities of all derivatives were evaluated against Staphylococcus aureus, Micrococcus luteus, and the mouse cell line L929.     

Differentiating between Models of Epothilone Binding to Microtubules Using Tubulin Mutagenesis, Cytotoxicity, and Molecular Modeling

Microtubule stabilizers are powerful antimitotic compounds and represent a proven cancer treatment strategy. Several classes of compounds in clinical use or trials, such as the taxanes and epothilones, bind to the same region of β‐tubulin. Determining how these molecules interact with tubulin and stabilize microtubules is important both for understanding the mechanism of action and enhancing chemotherapeutic potential, for example, minimizing side effects, increasing solubility, and overcoming resistance. Structural studies using non‐polymerized tubulin or stabilized polymers have produced different models of epothilone binding. In this study we used directed mutagenesis of the binding site on Saccharomyces cerevisiae β‐tubulin to analyze interactions between epothilone B and its biologically relevant substrate, dynamic microtubules. Five engineered amino acid changes contributed to a 125‐fold increase in epothilone B cytotoxicity independent of inherent microtubule stability. The mutagenesis of endogenous β‐tubulin was done in otherwise isogenic strains. This facilitated the correlation of amino acid substitutions with altered cytotoxicity using molecular mechanics simulations. The results, which are based on the interaction between epothilone B and dynamic microtubules, most strongly support the binding mode determined by NMR spectroscopy‐based studies. This work establishes a system for discriminating between potential binding modes and among various compounds and/or analogues using a sensitive biological activity‐based readout.     

Qualitative identification of permitted and non-permitted colour additives in food products

Colour additives are dyes, pigments or other substances that can impart colour when added or applied to food, drugs, cosmetics, medical devices, or the human body. The substances must be pre-approved by the US Food and Drug Administration (USFDA) and listed in Title 21 of the US Code of Federal Regulations before they may be used in products marketed in the United States. Some also are required to be batch certified by the USFDA prior to their use. Both domestic and imported products sold in interstate commerce fall under USFDA jurisdiction, and the USFDA's district laboratories use a combination of analytical methods for identifying or confirming the presence of potentially violative colour additives. We have developed a qualitative method for identifying 17 certifiable, certification exempt, and non-permitted colour additives in various food products. The method involves extracting the colour additives from a product and isolating them from non-coloured components with a C(18) Sep-Pak cartridge. The colour additives are then separated and identified by liquid chromatography (LC) with photodiode array detection, using an Xterra RP18 column and gradient elution with aqueous ammonium acetate and methanol. Limits of detection (LODs) ranged from 0.02 to 1.49 mg/l. This qualititative LC method supplements the visible spectrophotometric and thin-layer chromatography methods currently used by the USFDA's district laboratories and is less time-consuming and requires less solvent compared to the other methods. The extraction step in the new LC method is a simple and an efficient process that can be used for most food types.     

A Critique of Rolling Contact Fatigue Criteria for Bearing Rings with Hoop Stresses

Tensile residual and interference fit stresses not treated in classical bearing formulations are known to reduce bearing rolling contact fatigue (RCF) life. Recent modifications of such theory to account for these stresses have simply included them in the computation of a single yield stress type criterion—either maximum shear or equivalent stress. An alternative modification is proposed and demonstrated for fatigue crack initiation that recognizes the primary influence of the maximum range of shear stress but includes the effect of normal stress on the critical planes, as in other successful bulk fatigue criteria for multiaxial nonproportional stress cycle fatigue.     

Ascorbic acid,nitrate, and nitrite concentration relationship to the 24 hour light/dark cycle for spinach grown in different conditions

Nitrate, nitrite and ascorbic acid (vitamin C) concentrations were determined for spinach (Spinacia oleracea L.) over a 24 h period to determine if light intensity (including dark periods) at time of harvest impacts concentrations in raw vegetables. Nitrate, nitrate and ascorbic acid concentrations varied significantly over the 24 h period and appeared to be related to changes in light intensity. Light intensity at the time an experimental sample is collected may affect the concentration of some constituents that a researcher is studying. Also, nitrate and nitrite concentrations in raw spinach can be reduced by harvesting at the best time of day. The highest nitrate concentrations in spinach occurred in the dark just prior to an increase in light intensity. Ascorbic acid was near its highest level for the 24 h period when the light intensity initially increased, then decreased to its lowest level around 3–6 h later.     

扁平经纱在织机上无捻加工的解决方案

这个项目所取得的结果展示了如何采用扁平经纱织造致密面料的方法,这种方法既可实现高产量和高质量,又可改善材料的各种特性.因此,这种织物的应用领域可进一步拓展.这些改造采用的都是市场上有售的部件,无需特别的手段.改造之后,经轴和织造区之间的自由纱段最小化、经纱张力更均匀.经轴和织造区之间根据扁平纱的几何形状设置导纱器,并应用了特殊的综丝,明显减少或避免了经纱在整个经纱方向出现捻度.     

Influence of lamination process on optical fiber sensors embedded in composite material

In the paper we present the results of our research on optical fiber sensors embedded into composite material samples. We investigate the influence of the lamination process, axial orientation of an optical fiber sensor and coating of a fiber on stress monitoring of a composite material. In the paper we present two approaches to the case of composite condition monitoring, using a polarimetric fiber optic sensor as well as fiber Bragg gratings. We also present experimental evidence that interaction between a composite material and fiber optic sensors is very significant and depends on many factors such as fiber optic axial orientation and the coating layer surrounding an optical fiber.     

The Production of Conjugated α-Linolenic, γ-Linolenic and Stearidonic Acids by Strains of Bifidobacteria and Propionibacteria

Conjugated fatty acids are regularly found in nature and have a history of biogenic activity in animals and humans. A number of these conjugated fatty acids are microbially produced and have been associated with potent anti-carcinogenic, anti-adipogenic, anti-atherosclerotic and anti-diabetogenic activities. Therefore, the identification of novel conjugated fatty acids is highly desirable. In this study, strains of bifidobacteria and propionibacteria previously shown by us and others to display linoleic acid isomerase activity were assessed for their ability to conjugate a range of other unsaturated fatty acids during fermentation. Only four, linoleic, α-linolenic, γ-linolenic and stearidonic acids, were converted to their respective conjugated isomers, conjugated linoleic acid (CLA), conjugated α-linolenic acid (CLNA), conjugated γ-linolenic acid (CGLA) and conjugated stearidonic acid (CSA), each of which contained a conjugated double bond at the 9,11 position. Of the strains assayed, Bifidobacterium breve DPC6330 proved the most effective conjugated fatty acid producer, bio-converting 70% of the linoleic acid to CLA, 90% of the α-linolenic acid to CLNA, 17% of the γ-linolenic acid to CGLA, and 28% of the stearidonic acid to CSA at a substrate concentration of 0.3 mg mL⁻¹. In conclusion, strains of bifidobacteria and propionibacteria can bio-convert linoleic, α-linolenic, γ-linolenic and stearidonic acids to their conjugated isomers via the activity of the enzyme linoleic acid isomerase. These conjugated fatty acids may offer the combined health promoting properties of conjugated fatty acids such as CLA and CLNA, along with those of the unsaturated fatty acids from which they are formed.