Biotinylated nanodiamond: simple and efficient functionalization of detonation diamond

We have developed a simple and efficient method for the covalent functionalization of detonation nanodiamond. After homogenization of the surface by borane reduction, the surface was modified with (3-aminopropyl)trimethoxysilane. Subsequent grafting of biotin yielded covalently biotinylated nanodiamond, which was characterized by FTIR spectroscopy, X-ray powder diffractometry, thermogravimetry, and elemental analysis. The activity was tested with horseradish peroxidase-labeled streptavidin. The surface loading of biotin was found to be 1.45 mmol g-1. The new material opens the way to covalently bonded diamond bioconjugates for labeling, drug delivery, and other applications.     

Use of elevated flow rates in preparative subcritical fluid chromatography

The benefits of using high flow rates in preparative subcritical fluid chromatography are explored. It is demonstrated that chromatograms loaded to onset of peak coalescence do not deteriorate as flow increases. This allows separation of material in very short time periods leading to dramatically increased production rates. A key factor to accessing elevated flows is the use of shorter columns and the resulting decrease in pressure drop.     

Effect of the TAT-RasGAP(317-326) peptide on apoptosis of human malignant mesothelioma cells and fibroblasts exposed to meso-tetra-hydroxyphenyl-chlorin and light

BACKGROUND: 5,10,15,20-Tetrakis(m-hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy (PDT) has shown insufficient tumor selectivity for the treatment of pleural mesothelioma. Tumor selectivity of mTHPC-PDT may be enhanced in the presence of the TAT-RasGAP(317-326) peptide which has the potential to specifically sensitize tumor cells to cytostatic agents. MATERIALS AND METHODS: H-meso-1 and human fibroblast cell cultures, respectively, were exposed to two different mTHPC doses followed by light delivery with and without TAT-RasGAP(317-326) administration. mTHPC was added to the cultures at a concentration of 0.04microg/ml and 0.10microg/ml, respectively, 24h before laser light illumination at 652nm (3J/cm(2), 40mW/cm(2)). TAT-RasGAP(317-326) was added to the cultures immediately after light delivery at a concentration of 20microM. The apoptosis rate was determined by scoring the cells displaying pycnotic nuclei. Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: Light delivery associated with 0.04microg/ml mTHPC resulted in a significantly higher apoptosis rate in the presence of TAT-RasGAP(317-326) than without in H-meso-1 cells (p<0.05) but not in fibroblasts. In contrast, 1.0microg/ml mTHPC and light resulted in a significantly higher apoptosis rate in both H-meso-1 cells and fibroblasts as compared to controls (p<0.05) but the addition of TAT-RasGAP(317-326) did not lead to a further significant increase of the apoptosis rate of both H-meso-1 cells and fibroblasts as compared to mTHPC and light delivery alone. CONCLUSION: TAT-RasGAP(317-326) selectively enhanced the effect of mTHPC and light delivery on H-meso-1 cells but not on fibroblasts. However, this effect was mTHPC dose-dependent and occurred only at a low sensitizer dose.     

Potential analytical applications of lysenin channels for detection of multivalent ions

Transmembrane protein transporters possessing binding sites for ions, toxins, pharmaceutical drugs, and other molecules constitute excellent candidates for developing sensitive and selective biosensing devices. Their attractiveness for analytical purposes is enhanced by the intrinsic amplification capabilities shown when the binding event leads to major changes in the transportation of ions or molecules other than the analyte itself. The large-scale implementation of such transmembrane proteins in biosensing devices is limited by the difficulties encountered in inserting functional transporters into artificial bilayer lipid membranes and by the limitations in understanding and exploiting the changes induced by the interaction with the analyte for sensing purposes. Here, we show that lysenin, a pore-forming toxin extracted from earthworm Eisenia foetida, which inserts stable and large conductance channels into artificial bilayer lipid membranes, functions as a multivalent ion-sensing device. The analytical response consists of concentration and ionic-species-dependent macroscopic conductance inhibition most probably linked to a ligand-induced gating mechanism. Multivalent ion removal by chelation or precipitation restores, in most cases, the initial conductance and demonstrates reversibility. Changes in lipid bilayer membrane compositions leading to the absence of voltage-induced gating do not affect the analytical response to multivalent ions. Microscopic current analysis performed on individual lysenin channels in the presence of Cu²⁺ revealed complex open–closed transitions characterized by unstable intermediate sub-conducting states. Lysenin channels provide an analytical tool with a built-in sensing mechanism for inorganic and organic multivalent ions, and the excellent stability in an artificial environment recommend lysenin as a potential candidate for single-molecule detection and analysis.     

Bi2223带材临界电流沿长度方向的统计分布

本文采用四引线法测量了Bi2223带材临界电流沿长度方向的分布,采用正态分布、对数正态分布、威布尔分布和最小极值分布对临界电流分布进行了拟合检验,确定了临界电流的最优统计分布模型.     

Comparative virtual screening and novelty detection for NMDA-GlycineB antagonists

Identification of novel compound classes for a drug target is a challenging task for cheminformatics and drug design when considerable research has already been undertaken and many potent lead structures have been identified, which leaves limited unclaimed chemical space for innovation. We validated and successfully applied different state-of-the-art techniques for virtual screening (Bayesian machine learning, automated molecular docking, pharmacophore search, pharmacophore QSAR and shape analysis) of 4.6 million unique and readily available chemical structures to identify promising new and competitive antagonists of the strychnine-insensitive Glycine binding site (Glycine_B site) of the NMDA receptor. The novelty of the identified virtual hits was assessed by scaffold analysis, putting a strong emphasis on novelty detection. The resulting hits were tested in vitro and several novel, active compounds were identified. While the majority of the computational methods tested were able to partially discriminate actives from structurally similar decoy molecules, the methods differed substantially in their prospective applicability in terms of novelty detection. The results demonstrate that although there is no single best computational method, it is most worthwhile to follow this concept of focused compound library design and screening, as there still can new bioactive compounds be found that possess hitherto unexplored scaffolds and interesting variations of known chemotypes.     

Vortex ring velocity and minimum separation in an infinite train of vortex rings generated by a fully pulsed jet

A pulsed jet with a period of no flow between pulses (i.e., a fully pulsed jet) produces a multiplicity of vortex rings whose characteristics are determined by the jet pulsing parameters. The present study analyzes the case of impulsively initiated and terminated jet pulses in the limit of equal pulse duration and period to determine the minimum possible vortex ring separation obtainable from a fully pulsed jet. The downstream character of the flow is modeled as an infinite train of thin, coaxial vortex rings. Assuming inviscid flow and matching the circulation, impulse, kinetic energy, and frequency of the jet and vortex ring train allow the properties of the vortex ring train to be determined in terms of the ratio of jet slug length-to-diameter ratio (L/D) used for each pulse. The results show the minimum ring separation may be made arbitrarily small as L/D is decreased and the corresponding total ring velocity remains close to half the jet velocity for L/D < 4, but the thin-ring assumption is violated for L/D > 1.5. The results are discussed in the context of models of pulsed-jet propulsion.     

Momentum evolution of ejected and entrained fluid during laminar vortex ring formation

The evolution of total circulation and entrainment of ambient fluid during laminar vortex ring formation has been addressed in a number of previous investigations. Motivated by applications involving propulsion and fluid transport, the present interest is in the momentum evolution of entrained and ejected fluid and momentum exchange among the ejected, entrained fluid and added mass during vortex ring formation. To this end, vortex rings are generated numerically by transient jet ejection for fluid slug length-to-diameter (L/D) ratios of 0.5–3.0 using three different velocity programs [trapezoidal, triangular negative slope (NS), and positive slope (PS)] at a jet Reynolds number of 1,000. Lagrangian coherent structures (LCS) were utilized to identify ejected and entrained fluid boundaries, and a Runge-Kutta fourth order scheme was used for advecting these boundaries with the numerical velocity data. By monitoring the center of mass of these fluid boundaries, momentum of each component was calculated and related to the total impulse provided by the vortex ring generator. The results demonstrate that ejected fluid exchanges its momentum mostly with added mass during jet ejection and that the momentum of the entrained fluid at jet termination was < 11% of the total ring impulse in all cases except for the triangular NS case. Following jet termination, momentum exchange was observed between ejected and entrained fluid yielding significant increase in entrained fluid’s momentum. A performance metric was defined relating the impulse from over-pressure developed at the nozzle exit plane during jet ejection to the flow evolution, which increased preferentially with L/D over the range considered. An additional benefit of this study was the identification of the initial (i.e., before jet initiation) location of the fluid to be entrained into the vortex ring.