Preparation and characterization of digoxin antibody and its application to immunoassays: comparison of performance characteristics between enzyme immunoassay and immunostrip test

After characterizing digoxin immunogens and antibodies, we investigated the assay performances of enzyme immunoassay (EIA), biotin–streptavidin mediated enzyme immunoassay (B-Av EIA), and immunostrip test and compared the effectiveness of these tests for detecting the presence of digoxin and its analogues. The clinical use of digoxin is very complicated due to its narrow therapeutic range. Thus, the development of a rapid and simple detection device has been needed. In our study, we determined digoxin levels by EIA and B-Av EIA, and compared these tests with the immunotest strip to determine the possibility of personal monitoring at the bedside. Three kinds of digoxin antibodies were produced from various digoxin–BSA immunogens (digoxin/BSA molar ratio of 15:1, 50:1, and 200:1 in their preparation step). The antibodies produced were purified by the immunoaffinity chromatography using digoxin–KLH or digoxin–BSA as the affinity ligand. Antibody #7 and its matching coating ligand of digoxin–KLH were selected by titration and sensitivity studies for use in EIA and B-Av EIA. Colloidal gold-labeled antibody #7 on a glass fiber membrane and digoxin–BSA on a nitrocellulose membrane were selected for the immunostrip preparation. The EIA and B-Av EIA could detect 0.01 ppb digoxin within 2.5 h, but the immunostrip could detect 0.01 ppm within 3 min, which was three orders less sensitive than EIA or B-Av EIA.     

Electrorheology of Multiwalled Carbon Nanotube/Poly(methyl methacrylate) Nanocomposites

Summary: Multiwalled carbon nanotube (MWNT) nanocomposites dispersed in a poly(methyl methacrylate) (PMMA) matrix were prepared via suspension polymerization, in which radicals induced on the outer wall of the MWNTs by 2,2′‐azoisobutyronitrile initiate the grafting of PMMA. The synthesized MWNT/PMMA nanocomposite particles were found to have a spherical shape and exhibit a high electrical conductivity, mainly as a result of the carbon nanotubes. A suspension was prepared with MWNT/PMMA particles in insulating silicone oil and its electrorheological properties were investigated by controlling applied direct current (DC) electric field strengths.

Flow curve possessing a region analogous to the coexistence curve.     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

关于BL-代数的模糊滤子与模糊理想

在BL-代数中引入模糊超滤子和模糊固执滤子的概念,证明了如下条件对于BL-代数的非常数模糊滤子f来说是等价的:(1)f是布尔的和素的,(2)f是蕴涵的和素的,(3)f是超的,(4)f是固执的。应用模糊正蕴涵滤子给出G-代数的若干特征性质。提出BL-代数模糊理想的概念,给出一些重要例子,并通过例子说明在BL-代数中模糊理想一般不能由模糊滤子导出。同时,从模糊理想出发构造了商BL-代数,并建立了相应的同态基本定理。最后,研究了BL-代数的几类模糊理想及其相互关系,给出模糊布尔理想、模糊素理想、模糊超理想的特征性质。     

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.Subject terms: Antibody therapy, Molecularly targeted therapy, Drug development     

On the ring loading problem with demand splitting

In this paper, we improve the rerouting step of Myung, Kim and Tcha's algorithm for the ring loading problem with demand splitting and achieve a better running time. We also conduct a computational study to evaluate the practical performance of the proposed algorithm.     

Dual problems for weak and quasi approximation properties

It is shown that for the separable dual X^∗ of a Banach space X if X^∗ has the weak approximation property, then X has the metric quasi approximation property. Using this it is shown that for the separable dual X^∗ of a Banach space X the quasi approximation property and metric quasi approximation property are inherited from X^∗ to X and for a separable and reflexive Banach space X, X having the weak approximation property, bounded weak approximation property, quasi approximation property, metric weak approximation property, and metric quasi approximation property are equivalent. Also it is shown that the weak approximation property, bounded weak approximation property, and quasi approximation property are not inherited from a Banach space X to X^∗.     

Location-area partition in a cellular radio network

With an increasing population of mobile subscribers, the signalling traffic to control the subscriber mobility expands rapidly. Subscriber mobility is controlled through location registration based on the so-called location area, the basic area unit for paging which consists of a number of cells. There is a tradeoff between the two kinds of signalling traffic: paging and location updating. As location areas include a larger number of cells, the traffic volume for paging increases while that for location updating decreases. Given not only the pattern of call arrivals but also that for subscriber mobility, our problem is to minimise the total signalling traffic by optimally partitioning the whole area into location areas. We show that this problem can be transformed to the so-called clique partitioning problem (CPP). Also we demonstrate the process of implementing the algorithm for solving the CPP for real-world problems defined on the cellular network in Seoul.