含电子媒介物的一次性葡萄糖传感器的响应性能

目前,适合于测量体内、外生理溶液中葡萄糖浓度的葡萄糖检测装置中,国外便携式产品占据全部国内市场,其中绝大部分是基于比色原理,近些年国外又推出一次性使用电化学葡萄糖传感器。基于葡萄糖传感器中新的测量电流方法,本文主要从材料选择和结构进行研究,以提高传感器的性能。本研究以水溶性高分子材料聚丙烯酰胺为载体,探讨加入电子媒介物铁氰化钾后,一次性传感器的各种影响因素及影响规律,并探索工作电极和参比电极为相同材料的可行性,为制作性能优良的一次性传感器提供依据。     

Engineering quadrupole magnetic flow sorting for the isolation of pancreatic islets

Quadrupole magnetic flow sorting (QMS) is being adapted from the separation of suspensions of single cells (<15 μm) to the isolation of pancreatic islets (150–350 μm) for transplant. To achieve this goal, the critical QMS components have been modeled and engineered to optimize the separation process. A flow channel has been designed, manufactured, and tested. The quadrupole magnet assembly has been designed and verified by finite element analysis. Pumps have been selected and verified by test. Test data generated from the pumps and flow channel demonstrate that the fabricated channel and peristaltic pumps fulfill the requirements of successful QMS separation.     

Functional improvement of porcine neonatal pancreatic cell clusters via conformal encapsulation using an air-driven encapsulator

Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 ± 2.88%) than that of naïve NPCCs and NPCCs in small capsule (86.83 ± 2.32%, 87.67 ± 2.07%, respectively) at day 7. The viability of naïve NPCCs decreased rapidly at day 14 (75.67 ± 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 ± 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 ± 0.09 and 2.13 ± 0.09) was conserved better compared to that of naïve NPCCs (2.04 ± 0.25 and 1.53 ± 0.32, respectively) and NPCCs in large capsules (2.04 ± 0.34 and 1.13 ± 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion.     

New leads for selective GSK-3 inhibition: pharmacophore mapping and virtual screening studies

Summary Glycogen Synthase Kinase-3 is a regulatory serine/threonine kinase, which is being targeted for the treatment of a number of human diseases including type-2 diabetes mellitus, neurodegenerative diseases, cancer and chronic inflammation. Selective GSK-3 inhibition is an important requirement owing to the possibility of side effects arising from other kinases. A pharmacophore mapping strategy is employed in this work to identify new leads for selective GSK-3 inhibition. Ligands known to show selective GSK-3 inhibition were employed in generating a pharmacophore map using distance comparison method (DISCO). The derived pharmacophore map was validated using (i) important interactions involved in selective GSK-3 inhibitions, and (ii) an in-house database containing different classes of GSK-3 selective, non-selective and inactive molecules. New Lead identification was carried out by performing virtual screening using validated pharmacophoric query and three chemical databases namely NCI, Maybridge and Leadquest. Further data reduction was carried out by employing virtual filters based on (i) Lipinski’s rule of 5 (ii) van der Waals bumps and (iii) restricting the number of rotatable bonds to seven. Final screening was carried out using FlexX based molecular docking study.     

Comparison of a homology model and the crystallographic structure of human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) in a structure-based identification of inhibitors

Summary Human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes the interconversion of cortisone into active cortisol. 11βHSD1 inhibition is a tempting target for the treatment of a host of human disorders that might benefit from blockade of glucocorticoid action, such as obesity, metabolic syndrome, and diabetes type 2. Here, we report an in silico screening study aimed at identifying new selective inhibitors of human 11βHSD1 enzyme. In the first step, homology modeling was employed to build the 3D structure of 11βHSD1. Further, molecular docking was used to validate the predicted model by showing that it was able to discriminate between known 11βHSD1 inhibitors or substrates and non-inhibitors. The homology model was found to reproduce closely the crystal structure that became publicly available in the final stages of this work. Finally, we carried out structure-based virtual screening experiments on both the homology model and the crystallographic structure with a database of 114’000 natural molecules. Among these, 15 molecules were consistently selected as inhibitors based on both the model and crystal structures of the enzyme, implying a good quality for the homology model. Among these putative 11βHSD1 inhibitors, two were flavonone derivatives that have already been shown to be potent inhibitors of the enzyme.     

Synthesis of urea acetates as potential PPARα/γ,dual agonists

In the quest for novel PPARα/γ dual agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia,we designed and synthesized a series of urea acetates as potential PPARα/γ dual agonists.The structure of the target compounds,intermediates were characterized by 1H NMR,HRMS.     

Exact Misclassification Probabilities for Plug-In Normal Quadratic Discriminant Functions: II. The Heterogeneous Case

We consider the problem of discriminating between two independent multivariate normal populations, N_p(μ₁, Σ₁) and N_p(μ₂, Σ₂), having distinct mean vectors μ₁ and μ₂ and distinct covariance matrices Σ₁ and Σ₂. The parameters μ₁, μ₂, Σ₁, and Σ₂ are unknown and are estimated by means of independent random training samples from each population. We derive a stochastic representation for the exact distribution of the “plug-in” quadratic discriminant function for classifying a new observation between the two populations. The stochastic representation involves only the classical standard normal, chi-square, and F distributions and is easily implemented for simulation purposes. Using Monte Carlo simulation of the stochastic representation we provide applications to the estimation of misclassification probabilities for the well-known iris data studied by Fisher (Ann. Eugen.7 (1936), 179–188); a data set on corporate financial ratios provided by Johnson and Wichern (Applied Multivariate Statistical Analysis, 4th ed., Prentice–Hall, Englewood Cliffs, NJ, 1998); and a data set analyzed by Reaven and Miller (Diabetologia16 (1979), 17–24) in a classification of diabetic status.