Synthesis,Biological Evaluation of 1,1‐Diarylethylenes as a Novel Class of Antimitotic Agents

The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B‐ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA‐4 ( 2 e ), isoCA‐4 ( 2 k ) and isoNH₂CA‐4 ( 2 s ) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC₅₀ values of 4, 2 and 1.5 μM , respectively. These derivatives were found to be 10‐fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G₂/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e , 2 k and 2 s on the vessel‐like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors.     

An Effect of Temperature and Notch Geometry on Correlated Toughness of a Stainless Steel

To determine the toughness of materials, Charpy V notch test has been widely used over the world. Originally, the Charpy-V or U tests were used mainly as a quality control tests. In this paper, effects of temperature and notch geometry on variation of toughness/yield stress ratio were investigated. The experimental work has been performed on austenitic stainless steel 316L using Charpy tests and carried out at temperature range from 20 ℃ to 250 ℃ on different dimension of V- and U-notch specimens. Energy of fracture was determined directly from machine tests. Furthermore, Barsoum correlation has been applied to determine toughness/yield stress ratio as function of temperature. In addition, several parameters were investigated namely specimen thickness and notch cut angles. U-notch specimen offers a high resistance comparatively to the V-notch and that toughness depends on temper situation and orientation of notch relative to the rolling direction.     

A hybrid analytical model for the transverse vibration response of a micro-end mill

As a result of its detrimental effect on tool life and product quality, vibration analyses are crucial if the full potential of micro-milling operation is to be attained. In this paper, a hybrid analytical model (HAM) developed for estimating the transverse response of a micro-end mill is presented. The HAM is a combination of discrete and distributed structural elements. The discrete elements account for the stiffness and damping coefficients of the machining system, while the distributed elements idealize the geometrical representation of the micro-end mill with a novel model of the micro-flute. A number of slot micro-end milling operations, carefully designed with the Taguchi method of design of experiments, are carried out to examine the accuracy of the HAM. The comparison of the response profile from the experiment and the developed model shows reasonably close similarity. The influence of the helix angle is found to be far greater on the response of the micro-end mill than the other geometric variables. By making use of the root mean square of the response, it is further observed that the representation of the micro-flute of the micro-end mill with a less accurate model deteriorates the prediction of the HAM.     

Grid automata and supervisory control of dense real-time discrete event systems

We present a generalization of the classical supervisory control theory for discrete event systems to a setting of dense real-time systems modeled by Alur and Dill timed automata. The main problem involved is that in general the state space of a timed automaton is (uncountably) infinite. The solution is to reduce the dense time transition system to an appropriate finite discrete subautomaton, the grid automaton, which contains enough information to deal with the timed supervisory control problem (TSCP). The plant and the specifications region graphs are sampled for a granularity defined in a way that each state has an outgoing transition labeled with the same time amount. We redefine the controllability concept in the context of grid automata, and we provide necessary and sufficient solvability conditions under which the optimal solution to centralized supervisory control problems in timed discrete event systems under full observation can be obtained. The enhanced setting admits subsystem composition and the concept of forcible event. A simple example illustrates how the new method can be used to solve the TSCP.     

A Concern-based Technique for Architecture Modelling Using the UML Package Merge

In this paper, we present a concern-based technique for software architecture modelling. We use the new UML 2 Package Merge relationship as a technique for the separation of concerns. We present the advantages of using the UML Package Merge relationship for software architecture modelling, and we propose a set of extensions for its limitations.     

On the Electromagnetic Interference Fringes Method in Geophysical Prospecting Applications

The method of electromagnetic interference fringes for the prospecting of conductive subsurfaces inside the earth is reviewed. The fields radiated by an electrically small horizontal loop situated on the earth's surface are derived and expressed in terms of different interfering wave components. The variable distance interference fringes (VDIF) method and the variable frequency interference (VFIF) method of prospecting are considered, and an interpretation procedure using the data obtained from both methods is suggested.     

Stepwise Formation of Some Bivalent Metal Chelates with Sodium Alizarin Sulphonate

The stepwise protonation constants of the ligand and the stability constants of Alizarin Red S with some bivalent metal ions, Pb²⁺, Cu²⁺, Zn²⁺, and Hg²⁺ have been determined at 30° and at various ionic strengths viz. 0.02, 0.05, 0.15 and 0.20, maintained by sodium perchlorate solution. The formation of the chelate is evident from the shift between the (i) ligand and (ii) ligand and metal titration curves. From the values of the stepwise protonation constants and metal ligand stability constants at various ionic strengths, thermodynamic formation constants were evaluated by extrapolation to zero ionic strength. The order of stability constants was found to be: Cu > Pb > Zn > Hg     

Static and Dynamic Mechanical Behavior of Electron Beam‐Cured Monomer and Monomer/Liquid Crystal Systems

Summary: This paper discusses static and dynamic mechanical properties of electron beam‐cured mixtures made of the nematic liquid crystal (LC) E7 and either tripropyleneglycol diacrylate (TPGDA) or propoxylated glycerol triacrylate (GPTA) as monomers differing essentially by their functionality. Dilution of the initial mixture with LC leads to a significant weakening of the film mechanical strength. Strong effects were found on Young modulus and rubbery state modulus. As the concentration of LC increases, these mechanical parameters drop significantly together with the glass transition temperature of the polymer showing a plasticizing effect. The results for the glass transition temperatures for the polymer and the LC were confirmed by thermograms obtained by differential scanning calorimetry.

Storage tensile modulus versus temperature of EB‐cured TPGDA/E7 films for different LC concentrations.     

Goats' milk xanthine oxidoreductase is grossly deficient in molybdenum

Xanthine oxidoreductase (XOR) was purified from goats' milk. The u.v.-visible absorption spectrum was essentially identical to those of the corresponding bovine and human milk enzymes and showed an A280/A450 ratio of 5.20+/-0.12, indicating a high degree of purity. Like bovine and human milk XORs, enzyme purified from goats' milk showed a single band on SDS-PAGE corresponding to a subunit with approximate Mr 150,000. On Western blotting, mouse monoclonal anti-human XOR antibody cross-reacted with purified caprine and bovine XORs. The specific xanthine oxidase activity of goats' milk XOR, however, was very much lower than that of bovine XOR, although NADH oxidase activities of XOR from the two sources were similar. In these respects, the caprine milk XOR mirrors the human milk enzyme, in which case the kinetic effects have previously been attributed to relatively low molybdenum content. The molybdenum content of goats' milk XOR also was shown to be relatively low, with 0.09 atoms Mo per subunit, compared with 055 atoms Mo per subunit for the bovine enzyme. A parallel purification of human milk XOR showed 0.03 atoms Mo per subunit. The possible physiological significance of the low molybdenum content of the caprine milk enzyme and of its correspondingly low enzymic activity is discussed.     

Enrichment of cysteine-containing peptides from tryptic digests using a quaternary amine tag

A new strategy for specifically targeting cysteine-containing peptides in a tryptic digest is described. The method is based on quantitatively derivatizing cysteine residues with a quaternary amine tag (QAT). Tags were introduced into proteins following reduction of disulfide bonds through derivatization of cysteine residues with (3-acrylamidopropyl)trimethylammonium chloride. After trypsin digestion, derivatized cysteine-containing peptides were enriched by strong cation exchange chromatography. The method was validated using model peptides and a protein. The QAT strategy has several advantages over other methods for the selection of cysteine-containing peptides. One is that it increases the ionization efficiency of cysteine-containing peptides. The other is that chromatographic selection is achieved with simple, robust cation exchange chromatography columns. As a result, this new strategy provides a simple way to facilitate enrichment of cysteine-containing peptides, thereby reducing sample complexity in bottom-up proteomics.