Topological lower bounds on the distance between area preserving diffeomorphisms

Area preserving diffeomorphisms of the 2-disk which are Identity near the boundary form a group which can be equipped, using theL ²-norm on its Lie algebra, with a right invariant metric. In this paper we give a lower bound on the distance between diffeomorphisms which is invariant under area preserving changes of coordinates and which improves the lower bound induced by the Calabi invariant. In the case of renormalizable and infinitely renormalizable maps, our estimate can be improved and computed.     

一种基于图像处理技术获取尾流特性的新方法

提出了一种利用图像处理手段获取舰船尾流中气泡大小和密度的新方法.该方法对利用高速数字摄影设备拍摄的尾流图像进行处理;具有直观、实时、高效等特点,可以方便地应用在实际的工程项目中.     

Electrochemical Nano-Roughening of Gold Microstructured Electrodes for Enhanced Sensing in Biofluids**

A key challenge for sensor miniaturization is to create electrodes with smaller footprints, while maintaining or increasing sensitivity. In this work, the electroactive surface of gold electrodes was enhanced 30-fold by wrinkling followed by chronoamperometric (CA) pulsing. Electron microscopy showed increased surface roughness in response to an increased number of CA pulses. The nanoroughened electrodes also showed excellent fouling resistance when submerged in solutions containing bovine serum albumin. The nanoroughened electrodes were used for electrochemical detection of Cu²⁺ in tap water and of glucose in human blood plasma. In the latter case, the nanoroughened electrodes allowed highly sensitive enzyme-free sensing of glucose, with responses comparable to those of two commercial enzyme-based sensors. We anticipate that this methodology to fabricate nanostructured electrodes can accelerate the development of simple, cost-effective, and high sensitivity electrochemical platforms.     

Surface-Area Determination of Anisotropic Polymersomes by Amphiphilic Molecular Probe Loading

The surface area of anisotropic polymeric assemblies is a critical parameter concerning their properties. However, it is still a grand challenge for traditional techniques to determine the surface area. Here, a molecular probe loading (MPL) method is developed to measure the surface area of anisotropic polymersomes in the shape of tube, disc, and stomatocyte. This method uses an amphiphilic molecular probe, comprising hydrophobic pyrene as the anchor and hydrophilic tetraethylene glycol (EG₄) as the float. The surface area of spherical polymersomes determined by dynamic light scattering is quantitatively correlated with the loading amount of probes, allowing the calculation of the average separation distance between the loaded probes. With the separation distance, we successfully determine the surface area of anisotropic polymersomes by measuring the loading amount. We envision that the MPL method will assist in the real-time surface area characterization, enabling the customization of functions.     

Bioanalytical method validation,biopharmaceutical and pharmacokinetic evaluation of GSK-650394, a serum- and glucocorticoid-regulated kinase 1 inhibitor

GSK-650394 is an inhibitor of serum- and glucocorticoid-regulated kinase 1 that displays potency for treating cancer, hypertension, cardiovascular and neuronal diseases, such as Parkinson’s disease. However, the biopharmaceutical properties and pharmacokinetics of GSK-650394 have not been studied extensively. Also, there are currently no bioanalytical assays available for this new drug candidate. In this study, we developed a simple and sensitive liquid chromatography-tandem mass spectrometry method to quantify GSK-650394 in rat plasma and validated its selectivity, linearity, accuracy and precision, sensitivity, matrix effects, extraction recovery, and stability, following the United States Food and Drug Administration guidelines. In vitro studies showed the biopharmaceutical properties of GSK-650394, including its low solubility in water and simulated gastrointestinal fluids, passive transport in Caco-2 cell monolayers, high plasma protein binding, and primary metabolism by glucuronide conjugation in the small intestine and liver of rats. Following intravenous administration (2 mg/kg) to rats, GSK-650394 exhibited low total clearance (11.18 ± 1.28 mL/min/kg) and volume of distribution at steady-state (346.1 ± 120.6 mL/kg). Following oral administration (2, 5, and 10 mg/kg) to rats, GSK-650394 underwent enterohepatic circulation, with low bioavailability (～9%). The insignificant difference in bioavailability among three oral doses suggests that GSK-650394 may follow linear pharmacokinetics up to an oral dose of 10 mg/kg. In addition, the total form of parent drug and glucuronide conjugate in rat plasma from three oral doses showed a much higher value of area under the plasma concentration versus time curve than the parent drug, indicating that the primary metabolism process of GSK-650394 was glucuronidation. Our findings suggest that the low oral bioavailability of GSK-650394 is associated with its low solubility, instability under acidic gastric conditions, and extensive glucuronidation metabolism.