Optimization‐based framework for resin selection strategies in biopharmaceutical purification process development

This work addresses rapid resin selection for integrated chromatographic separations when conducted as part of a high‐throughput screening exercise during the early stages of purification process development. An optimization‐based decision support framework is proposed to process the data generated from microscale experiments to identify the best resins to maximize key performance metrics for a biopharmaceutical manufacturing process, such as yield and purity. A multiobjective mixed integer nonlinear programming model is developed and solved using the ε‐constraint method. Dinkelbach's algorithm is used to solve the resulting mixed integer linear fractional programming model. The proposed framework is successfully applied to an industrial case study of a process to purify recombinant Fc Fusion protein from low molecular weight and high molecular weight product related impurities, involving two chromatographic steps with eight and three candidate resins for each step, respectively. The computational results show the advantage of the proposed framework in terms of computational efficiency and flexibility. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1116–1126, 2017     

花卉脱毒培养与优质种苗生产

综述了自20世纪60年代以来花卉园艺植物离体快繁及脱毒培养技术的发展概况,着重讨论了外植体培养过程中以MS培养基补充植物激素的适宜范围及植物脱毒的主要方法。     

JPEG2000压缩算法及其在医学图像DICOM格式中的实现

本文描述了在医学图像DICOM格式中实现JPEG2000压缩算法的编程思路和方法。提供了部分VC＋＋代码,对关键函数进行了较详细的注解,并对两种图像压缩格式进行了比较,给出了一个详细的实验结果。     

A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies

Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4/7/10 have been obtained by the reaction of 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4(a-d) and 6-methyl uracil linked bis triazoles, 7(a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62–115.62 μM. Benzimidazolone bis triazoles, 10(a-n) showed better activity with MIC in the range 2.33–18.34 μM. Molecular modeling studies using Surflex-Dock algorithm supported our results.     

Prediction and analysis of protein methylarginine and methyllysine based on Multisequence features

Protein methylation, one of the most important post-translational modifications, typically takes place on arginine or lysine residue. The reversible modification involves a series of basic cellular processes. Identification of methyl proteins with their sites will facilitate the understanding of the molecular mechanism of methylation. Besides the experimental methods, computational predictions of methylated sites are much more desirable for their convenience and fast speed. Here, we propose a method dedicated to predicting methylated sites of proteins. Feature selection was made on sequence conservation, physicochemical/biochemical properties, and structural disorder by applying maximum relevance minimum redundancy and incremental feature selection methods. The prediction models were built according to nearest the neighbor algorithm and evaluated by the jackknife cross-validation. We built 11 and 9 predictors for methylarginine and methyllysine, respectively, and integrated them to predict methylated sites. As a result, the average prediction accuracies are 74.25%, 77.02% for methylarginine and methyllysine training sets, respectively. Feature analysis suggested evolutionary information, and physicochemical/biochemical properties play important roles in the recognition of methylated sites. These findings may provide valuable information for exploiting the mechanisms of methylation. Our method may serve as a useful tool for biologists to find the potential methylated sites of proteins.     

The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths

A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration (MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R₀), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission.     

Intergeneric somatic hybridization and its application to crop genetic improvement

Related or distant species of cultivated cs are a large pool of many desirable genes. Gene transfer from these species through conventional breeding is difficult owing to post- and pre-zygotic sexual incompatibilities. Somatic hybridization via protoplast fusion is a possible alternative for gene transfer from these species to cultivated crops. Since the early days of somatic hybridization many intergeneric somatic hybrids have been developed through symmetric fusion, asymmetric fusion and microfusion. Somatic hybrids are mainly selected by using markers such as specific media or fusion parents with special features, biochemical mutants, antibiotic resistance and complementation strategy. The hybridity of the regenerants is determined based on morphological, cytological and molecular analysis. The inheritance patterns of nuclear and cytoplasmic genomes in the somatic hybrids are diverse. Nuclear DNA from both fusion parents co-exists congruously in some hybrids with translocation and rearrangement of chromosomes, but spontaneous elimination of chromosomes from either or both fusion parents has been observed very often. In asymmetric fusion, chromosome elimination is an important issue that is a complicated process influenced by many factors, such as irradiation dose, phylogenetic relatedness, ploidy level of fusion parent and regenerants. As for chloroplast genome, uniparental segregation is mainly detected, though co-existence is also reported in some cases. The mitochondrial genome, in contrast to chloroplast, undergoes recombination and very frequent rearrangements. Somatic cell fusion has potential applications for crop genetic improvement by overcoming sexual incompatibility or reproductive barriers, and by realizing novel combinations of nuclear and/or cytoplasmic genomes.     

The gamma-frailty Poisson model for the nonparametric estimation of panel count data

In this article, we study nonparametric estimation of the mean function of a counting process with panel observations. We introduce the gamma frailty variable to account for the intracorrelation between the panel counts of the counting process and construct a maximum pseudo-likelihood estimate with the frailty variable. Three simulated examples are given to show that this estimation procedure, while preserving the robustness and simplicity of the computation, improves the efficiency of the nonparametric maximum pseudo-likelihood estimate studied in Wellner and Zhang (2000, Annals of Statistics 28, 779-814). A real example from a bladder tumor study is used to illustrate the method.     

Negritos, Australian aborigines, and the "proto-sundadont" dental pattern: the basic populations in east Asia, V.

Five evolutionarily significant dental traits were identified from a B-square distance analysis of nine crown characters recorded for several populations of East Asia and Oceania. Intergroup variation in these traits distinguishes three major divisions of the Mongoloid dental complex: sundadonty, sinodonty, and the dental pattern of Australian Aborigines. The Australian crown features may be characterized as having high frequencies of evolutionarily conservative characters. Negritos, one of the probable representatives of indigenous inhabitants of Southeast Asia who may have shared a common ancestor with Australians, possess the more derived sundadont dental pattern. As far as the five crown traits treated here are concerned, Australian dental features may be described as conforming to a "proto-sundadont" dental pattern, applying Turner's terminology. This pattern may represent a microevolutionary step prior to the emergence of the sundadont and sinodont patterns.