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31.
Bai R Nguyen TL Burnett JC Atasoylu O Munro MH Pettit GR Smith AB Gussio R Hamel E 《Journal of chemical information and modeling》2011,51(6):1393-1404
Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [(3)H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K(d) of 0.31 μM. We found no HB-induced aggregation of tubulin by high-performance liquid chromatography, even following column equilibration with HB. Binding of [(3)H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K(i), 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K(i)'s, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds. 相似文献
32.
Nguyen Van Luong Nguyen Xuan Thuan 《Nonlinear Analysis: Theory, Methods & Applications》2011,74(3):983-992
In this paper, we prove some coupled fixed point theorems for mappings having a mixed monotone property in partially ordered metric spaces. The main results of this paper are generalizations of the main results of Bhaskar and Lakshmikantham [T. Gnana Bhaskar, V. Lakshmikantham, Fixed point theorems in partially ordered metric spaces and applications, Nonlinear Anal. TMA 65 (2006) 1379-1393]. As an application, we discuss the existence and uniqueness for a solution of a nonlinear integral equation. 相似文献
33.
Semigroup Forum - In this paper we present a simple spectral theory of polynomially bounded functions on the half line, and then apply it to study the asymptotic behavior of solutions of fractional... 相似文献
34.
Bacillus thuringiensis and recombinant Escherichia coli proteinaceous protoxins were subject to proteolysis and analyzed by capillary electrokinetic chromatography. Three resulting toxins (65 kDa) were baseline-resolved within 22 min using a 10 mM borate, pH 11 separation buffer consisting of 25 mM sodium dodecyl sulfate (SDS) and 30 mM phytic acid. The toxins displayed differential interactions with the SDS and phytic acid phases to effect their separation. The ion-pairing interaction between the analyte and phytic acid was also useful in preventing adsorption to the capillary walls and thus enhanced separation resolution and efficiency. The use of electrokinetic chromatography allows achievement of the separation in a significantly shorter time than conventional high-performance liquid chromatography (HPLC) using a diethylaminoethyl (DEAE) weak-anion exchanger. 相似文献
35.
Ronda Gras Yujuan Hua Jim Luong Peiqi Qiao Xiuhan Grace Yang Peilin Yang 《Journal of separation science》2019,42(17):2826-2834
A gas chromatographic approach for the determination and quantification of trace levels of carbon oxides in gas phase matrices for in situ or near‐line/at‐line analysis has been successfully developed. Catalytic conversion of the target compounds to methane via the methanation process was conducted inside a metal 3D‐printed jet that also acted as a hydrogen burner for the flame ionization detector. Modifications made to a field transportable gas chromatograph enabled the leveraging of advantaged microfluidic‐enhanced chromatography capability for improved chromatographic performance and serviceability. The compatibility with adsorption chromatography technology was demonstrated with in‐house constructed columns. Sustained reliable conversion efficiencies of greater than 99% with respectable peak symmetries were attained at 400°C. Quantification of carbon monoxide and carbon dioxide at a parts‐per‐million level over a range from 0.2 ppm to 5% v/v for both compounds with a respectable precision of less than 3% relative standard deviation for peak area (n = 10) and a detection limit of 0.1 ppm v/v was achieved. Linearity with correlation coefficients of R2 greater than 0.9995 and measured recoveries of >99% for spike tests were achieved. The 3D‐printed steel jet was found to be reliable and resilient against potential contamination from the matrices owing to the in situ backflushing capability. 相似文献
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In this paper, a computational study using the moving element method (MEM) is carried out to investigate the dynamic response of a high-speed rail (HSR) traveling at non-uniform speeds. A new and exact formulation for calculating the generalized mass, damping and stiffness matrices of the moving element is proposed. Two wheel–rail contact models are examined. One is linear and the other nonlinear. A parametric study is carried out to understand the effects of various factors on the dynamic amplification factor (DAF) in contact force between the wheel and rail such as the amplitude of acceleration/deceleration of the train, the severity of railhead roughness and the wheel load. Resonance in the vibration response can possibly occur at various stages of the journey of the HSR when the speed of the train matches the resonance speed. As to be expected, the DAF in contact force peaks when resonance occurs. The effects of the severity of railhead roughness and the wheel load on the occurrence of the jumping wheel phenomenon, which occurs when there is a momentary loss of contact between the wheel and track, are investigated. 相似文献
39.
2-D GC is a logical and cost effective extension to 1-D GC for improving the separation resolution, selectivity, and peak capacity of an analytical system. The advent of electronic pressure control systems that are accurate to the third decimal place, combined with recently innovated chromatographic devices such as capillary flow technology, has eliminated many deficiencies encountered in current conventional 2-D GC by making the technique reliable and simple to implement in both production and research analytical facilities. Low thermal mass GC (LTM-GC) was successfully integrated with capillary flow technology to further enhance overall 2-D GC chromatographic system performance by providing not only faster throughput via rapid heating and cooling, but independent temperature control for each dimension to maximize separation power. As an example, despite the enhanced peak capacity obtained from conventional 2-D GC, alkyl naphthalene isomers such as 2,3-dimethyl and 1,4-dimethyl naphthalene coeluted. These two critical compounds were well resolved (R = 5.2) using 2-D GC with LTM-GC with a similar analytical time. This paper demonstrates the benefits of combining capillary flow technology with LTM-GC to provide major enhancements to conventional 2-D GC. The synergy of these techniques is highlighted with practical industrial applications. 相似文献
40.
Electrodeposition of Pt-Pb nanoparticles (PtPbNPs) to multi-walled carbon nanotubes (MWCNTs) resulted in a stable PtPbNP/MWCNT nanocomposite with high electrocatalytic activity to glucose oxidation in either neutral or alkaline medium. More importantly, the nanocomposite electrode with a slight modification exhibited high sensitivity, high selectivity, and low detection limit in amperometric glucose sensing at physiological neutral pH (poised at a negative potential). At +0.30 V in neutral solution, the nanocomposite electrode exhibited linearity up to 11 mM of glucose with a sensitivity of 17.8 μA cm−2 mM−1 and a detection limit of 1.8 μM (S/N = 3). Electroactive ascorbic acid (0.1 mM), uric acid (0.1 mM) and fructose (0.3 mM) invoked only 23%, 14% and 9%, respectively, of the current response obtained for 3 mM glucose. At −0.15 V in neutral solution, the electrode responded linearly to glucose up to 5 mM with a detection limit of 0.16 mM (S/N = 3) and detection sensitivity of ∼18 μA cm−2 mM−1. At this negative potential, ascorbic acid, uric acid, and fructose were not electroactive, therefore, not interfering with glucose sensing. Modification of the nanocomposite electrode with Nafion coating followed by electrodeposition of a second layer of PtPbNPs on the Nafion coated PtPbNP/MWCNT nanocomposite produced a glucose sensor (poised at −0.15 V) with a lower detection limit (7.0 μM at S/N = 3) and comparable sensitivity, selectivity and linearity compared to the PtPbNP/MWCNT nanocomposite. The Nafion coating lowered the detection limit by reducing the background noise, while the second layer of PtPbNPs restored the sensitivity to the level before Nafion coating. 相似文献