Amphiphilic Copolymers Shuttle Drugs Across the Blood–Brain Barrier

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood–brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non‐water‐soluble and brain‐impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N‐(2‐hydroxypropyl)‐methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48‐fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.

     

Sequence-based analysis of 5′UTR and coding regions of CASP3 in terms of miRSNPs and SNPs in targetting miRNAs

Apoptosis is described as a mechanism of cell death occurring after adequate cellular harm. Deregulation of apoptosis occurs in many human conditions such as autoimmune disorders, ischemic damage, neurodegenerative diseases and different cancer types. Information relating miRNAs to cancer is increasing. miRNAs can affect development of cancer via many different pathways, including apoptosis. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Although polymorphisms in miRNA genes are very uncommon, SNPs in miRNA-binding sites of target genes are quite common. Many researches have revealed that SNPs in miRNA target sites improve or decrease the efficacy of the interaction between miRNAs and their target genes. Our aim was to specify miRSNPs on CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 5′UTR and coding exons of CASP3, and evaluate the effect of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. We detected 141 different miRNA binding sites (126 different miRNAs) and 7 different SNPs in binding sites of miRNA in 5′UTR and CDS of CASP3 gene. Intriguingly, miR-339-3p’s binding site on CASP3 has a SNP (rs35372903, G/A) on CASP3 5′UTR and its genomic sequence has a SNP (rs565188493, G/A) at the same nucleotide with rs35372903. Also, miR-339-3p has two other SNPs (rs373011663, C/T rs72631820, A/G) of which the first is positioned at the binding site. Here, miRSNP (rs35372903) at CASP3 5′UTR and SNP (rs565188493) at miR-339-3p genomic sequence cross-matches at the same site of binding region. Besides, miR-339-3p targets many apoptosis related genes (ZNF346, TAOK2, PIM2, HIP1, BBC3, TNFRSF25, CLCF1, IHPK2, NOL3) although it had no apoptosis related interaction proven before. This means that miR-339-3p may also have a critical effect on apoptosis via different pathways other than caspase-3. Hence, we can deduce that this is the first study demonstrating a powerful association between miR-339-3p and apoptosis upon computational analysis.     

Statistical optimization of conditions for protease production fromBacillus sp. and its scale-up in a bioreactor

A statistical approach, response surface methodology (RSM), was used to study the production of extracellular protease fromBacillus sp., which has properties of immense industrial importance. The most influential parameters for protease production obtained through the method of testing the parameters one at a time were starch, soybean meal, CaCl₂, agitation rate, and inoculum density. This method resulted in the production of 2543 U/mL of protease in 48 h fromBacillus sp. Based on these results, face-centered central composite design falling under RSM was employed to further enhance protease activity. The interactive effect of the most influential parameters resulted in a 1.50-fold increase in protease production, yielding 3746 U/mL in 48 h. Analysis of variance showed the adequacy of the model and verification experiments confirmed its validity. On subsequent scale-up in a 30-L bioreactor using conditions optimized through RSM, 3978 U/mL of protease was produced in 18 h. This clearly indicated that the model remained valid even on a large scale. RSM is a quick process for optimization of a large number of variables and provides profound insight into the interactive effect of various parameters involved in protease production.     

Proximate Composition,Antioxidant Properties,and Hepatoprotective Activity of Three Species of Shellfish of the Pacific Coast of Russia

The objective of the present study was to investigate the proximate composition, antiradical properties and hepatoprotective activity of three species of shellfish, Corbicula japonica, Spisula sachalinensis, and Anadara broughtonii, from the coastal areas of Far East Russia. Biologically active peptides such as taurine (3.74 g/100 g protein) and ornithine (2.12 g/100 g protein) have been found in the tissues of A. broughtonii. C. japonica contains a high amount of ornithine (5.57 g/100 g protein) and taurine (0.85 g/100 g protein). The maximum DPPH and ABTS radical scavenging activity (36.0 µg ascorbic acid/g protein and 0.68 µmol/Trolox equiv/g protein, respectively) was determined for the tissue of C. japonica. The protein and peptide molecular weight distribution of the shellfish tissue water extracts was investigated using HPLC. It was found that the amount of low molecular weight proteins and peptides were significantly and positively correlated with radical scavenging activity (Pearson’s correlation coefficient = 0.96), while the amount of high molecular weight proteins negatively correlated with radical scavenging activity (Pearson’s correlation coefficient = −0.86). Hepatoprotective activity, measured by the survival rate of HepG2 hepatocytes after cotreatment with t-BHP, was detected for C. japonica. The highest protection (95.3 ± 2.4%) was achieved by the cold water extract of C. japonica at the concentration of 200 mg/mL. Moreover, oral administration of hot water extract of C. japonica to rats before the treatment with CCl₄ exhibited a markedly protective effect by lowering serum levels of ALT and AST, inhibiting the changes in biochemical parameters of functional state of rat liver, including MDA, SOD, GSH and GST.     

A Capacity-Achieving Feedback Scheme of the Gaussian Multiple-Access Channel with Degraded Message Sets

The classical Schalkwijk–Kailath (SK) scheme for the point-to-point white Gaussian channel with noiseless feedback plays an important role in information theory due to the fact that it is capacity-achieving and the complexity of its encoding–decoding procedure is extremely low. In recent years, it has been shown that an extended SK feedback scheme also achieves the capacity region of the two-user Gaussian multiple-access channel with noiseless feedback (GMAC-NF), where two independent messages are, respectively, encoded by two intended transmitters. However, for the two-user GMAC-NF with degraded message sets (one common message for both users and one private message for an intended user), the capacity-achieving feedback scheme remains open. In this paper, we propose a novel two-step SK-type feedback scheme for the two-user GMAC-NF with degraded message sets and show that this scheme is capacity-achieving.     

Measuring and Controlling Bias for Some Bayesian Inferences and the Relation to Frequentist Criteria

A common concern with Bayesian methodology in scientific contexts is that inferences can be heavily influenced by subjective biases. As presented here, there are two types of bias for some quantity of interest: bias against and bias in favor. Based upon the principle of evidence, it is shown how to measure and control these biases for both hypothesis assessment and estimation problems. Optimality results are established for the principle of evidence as the basis of the approach to these problems. A close relationship is established between measuring bias in Bayesian inferences and frequentist properties that hold for any proper prior. This leads to a possible resolution to an apparent conflict between these approaches to statistical reasoning. Frequentism is seen as establishing figures of merit for a statistical study, while Bayes determines the inferences based upon statistical evidence.     

Computation methods for combinatorial sums and Euler‐type numbers related to new families of numbers

The aim of this article is to define some new families of the special numbers. These numbers provide some further motivation for computation of combinatorial sums involving binomial coefficients and the Euler kind numbers of negative order. We can show that these numbers are related to the well‐known numbers and polynomials such as the Stirling numbers of the second kind and the central factorial numbers, the array polynomials, the rook numbers and polynomials, the Bernstein basis functions and others. In order to derive our new identities and relations for these numbers, we use a technique including the generating functions and functional equations. Finally, we give not only a computational algorithm for these numbers but also some numerical values of these numbers and the Euler numbers of negative order with tables. We also give some combinatorial interpretations of our new numbers. Copyright © 2016 John Wiley & Sons, Ltd.     

中心零可换环

本文给出了中心零可换环而非中心半交换环的例子,否定地回答了Jung等人在文[Bull.Korean Math.Soc.2015,52(1):247-261]中的一个问题.并证明了如果R是中心约化环,那么对任意正整数n,R[x]/(x~n)是中心对称环.     

基于PSR-PCA模型的京津冀区域大气环境治理绩效评价实证研究

随着我国工业化和新型城镇化建设进程的不断加快,资源和环境问题对于经济发展的制约和限制性作用日益凸显,其中大气污染问题首当其冲.而京津冀地区恰恰是我国大气污染最为严重的地区之一.为了对京津冀大气污染治理进行整体综合绩效评价,以环境资源管理的PSR模型为基础构建了京津冀区域大气污染治理绩效评价指标体系,并结合主成分分析法(PCA)对京津冀地区13个城市2013-2015年的大气污染治理绩效进行了实证分析.