Existence of a globally asymptotically stable equilibrium in Volterra models with continuous time delay

A sufficient condition for the existence of a globally asymptotically stable equilibrium in Volterra models with continuous time delay is obtained, and some properties of the stable equilibrium are proven. Furthermore, some applications in which asymptotic stability only depends on the sign of the coefficients are considered.     

Extreme value analysis in biometrics

We review some approaches of extreme value analysis in the context of biometrical applications. The classical extreme value analysis is based on iid random variables. Two different general methods are applied, which will be discussed together with biometrical examples. Different estimation, testing, goodness‐of‐fit procedures for applications are discussed. Furthermore, some non‐classical situations are considered where the data are possibly dependent, where a non‐stationary behavior is observed in the data or where the observations are not univariate. A few open problems are also stated.     

Use of PCR in the field

Polymerase chain reaction (PCR) represents a powerful new technology with a variety of field applications. While most of these are still experimental, implementation of PCR-based detection of Onchocerca volvulus in black flies, and subspecific differentiation strongly suggest that potential problems can be overcome. Because of high sensitivity and specificity, PCR provides in some cases the only means to address central parasitological questions, and may well become the 'gold standard' by which other diagnostic techniques are measured. In spite of these advantages, routine implementation of PCR,at present,requires transportation of samples to a central facility for processing, and personnel whose technical competence is high. In addition, reagents are expensive. Robert Barker here weighs up these considerations with regard to the potential utility of PCR assays for some applications.     

Molecular genetics and the management and conservation of marine organisms

Biochemical and molecular species identification techniques have a broad range of applications in the management and conservation of marine organisms. While species boundaries are not always clearly defined, phylogeneticists utilise autapomorphic characters to distinguish phylogenetic species. Genetic markers discriminate between marine taxa when traditional morphological distinctions are unclear. The applications of these techniques can be divided into four general categories. Firstly, compliance enforcement, which often depends on genetic identification techniques to enable officials to identify the species to which regulations pertain. Secondly, quality control applications, to allow for the testing of marine products to guard against fraudulent substitution with less valuable species, which is particularly pertinent since processing often obliterates identifiable features. Thirdly, a variety of applications to ecological and life-history studies and conservation management are reported. Here, the genetic identification techniques of species from cryptic life-cycle stages or of morphologically indistinct species are an indispensable tool for marine scientists, conservators and managers. Lastly, the application of genetic techniques for sourcing population origin is briefly discussed. The biochemical and molecular techniques applied to species identification all exploit phenotypic or genotypic polymorphisms that are sampled using either tertiary level protein based methods or primary level DNA based methods. In this review, examples of the applications along with the total protein, allozyme, serological, PCR and other DNA based methodologies are briefly described and some generalities with regard to their use are presented.     

Developments in enzyme technology

Enzyme technology has a well established industrial base with applications which have survived the test of time in a competitive market place. In this review a number of the most prominent applications of enzymes in the wide field of Biotechnology are examined together with a brief exposition of some of the theoretical background.     

Unique analytical capabilities of laser scanning cytometry (LSC) that complement flow cytometry

Flow cytometry has become an indispensable instrumentation in many disciplines of biology and medicine. There are some limitations of flow cytometry, inherent to the fact that the cells are measured in flow, which limit its usefulness in some applications. The microscope-based laser scanning cytometer (LSC) has many features similar to flow cytometry but few restrictions of the latter and therefore it is useful in many new applications. This review briefly outlines the applications that are unique to LSC, particularly related to its morphometric capabilities and the possibility of cell relocation. Potential future applications of LSC are also discussed.     

The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice

Groups of hairless mice received one, two, five and fifty applications of 20 nmoles TPA (12-0-tetradecanoylphorbol-13-acetate) on the skin of the back, and were observed for 20 months. The animals developed some papillomas, some squamous cell carcinomas, some fibrosarcomas of the dermis, and some malignant and benign tumours in internal organs. There was a small, not significantly different, incidence of benign and malignant tumours after 1, 2 and 5 paintings, and a significantly higher tumour incidence after 50 applications. Apart from reticuloses, which are commonly seen in these animals, the occurrence of other tumours is believed to be related to the TPA treatment. The results are interpreted as showing that TPA, like croton oil, should be regarded as a complete carcinogen.     

光片荧光显微镜特点及其应用

传统荧光显微镜由于对某些荧光分子存在光毒性、光损伤等方面的缺陷,无法满足对部分活体样本进行长时间观测的需求。光片荧光显微镜（light sheet fluorescence microscope,LSFM）是一种新型荧光显微镜,有别于激光共聚焦显微镜,其特殊的正交光路设计和高效的信号采集装置,使其具备低光毒性、低光漂白、低光损伤和高时空分辨率等优良特性,从而能对细胞及大尺度生物组织样本进行时空连续性较好的记录,尤其适宜于活体生物样品。基于此,概述了光片荧光显微镜的成像原理、成像优势、成像效果的改进与优化历程及其在生命科学领域应用所取得的研究成果,重点对近三年相关应用进行了汇总,并简要介绍了其在神经生物学、发育生物学、动物细胞生物学和植物科学领域中一部分代表性研究内容,最后,总结了光片荧光显微镜的优点与发展至今仍存在的不足,并对其在光遗传学和多组学研究中的潜在应用进行了展望,以期为研究人员提供较为系统的光片荧光显微镜相关基础知识、最新的研究应用进展以及未来的潜在应用方向,为研究人员提供参考。     

Hepatic microsomal enzymes: Potential applications

In contrast to the enzymes presently used in industrial applications, only a few hepatic microsomal enzymes have been isolated and characterized sufficiently to consider potential applications. When compared to the enzymes used for example by the sugar industry, the microsomal enzymes are more unstable, more difficult to purify, exhibit very low reaction rates, and usually require expensive cofactors or cosubstrates. However, microsomal enzymes have some unique properties which lend themselves to applications in the areas of pharmacology, medicine, and identification of potentially carcinogenic or toxic metabolites of foreign compounds. This paper reviews briefly some of these applications.     

iPSCs来源的血细胞在血液系统疾病中的应用与发展

骨髓（BM）移植已在许多血液病中成功应用多年,主要依赖于成人BM和外周血（PB）中的造血干细胞（HSCs）。然而,合适配型HSCs的稀缺限制了其临床应用,难以满足更多有需要的患者。诱导多能干细胞（iPSCs）的出现,有望解决这一难题。iPSCs具有分化成所有血细胞的潜能,使得HSCs和其他血细胞在血液病中的广泛应用成为可能。然而,临床应用iPSCs治疗血液病仍障碍重重。本文主要回顾了iPSCs在血液病中的应用和发展以及面临的问题和挑战。     

Practical applications of the microphotometric quantification of histoenzyme reactions

Summary There are many histochemical reactions which can be used for the accurate topographic detection of enzymes in tissues. There are also many reports of applications of these techniques in which the results have been evaluated subjectively. However, only a few of these methods have been the subject of quantification, using different methodologies, most of them based on microphotometry. A critical analysis of these procedures has generally shown that they are valid either relatively or at an absolute level. Nevertheless, the routine application of these methods is not as widespread as one might expect.In this paper, the methodological developments that have taken place in the histochemical assay of some enzymes by microspectrophotometry are reviewed briefly. The enzymes include acid phosphatase, non-specific esterase, succinate dehydrogenase and cytochrome oxidase. These methods have given consistent and useful results when applied to our experimental models of irradiated skin, and thus seem useful for various other applications.The reasons why there have been so few applications of quantitative histochemistry are also discussed together with possible ways of making its use more general.     

Liquid emulsion membranes: principles, problems and applications in fermentation processes

Liquid emulsion membranes (LEMs) have developed into a versatile technique for a variety of applications involving selective and controlled transport of biochemicals. Biological applications cover the controlled delivery of drugs from capsules, detoxification of the circulatory system, recovery of useful compounds from waste streams and selective separation of products from fermentation broths. This review traces the development of LEMs, discusses their key features, advantages and limitations, describes methods of modelling LEM systems and highlights some applications with industrial potential.Two kinds of LEM systems are considered. The first type are agitated emulsions, which are relatively easy to prepare and use but may be limited in their selectivity and long-term stability. Supported liquid membranes (SLMs) are a recent development; they use porous solid supports and have excellent stability and selectivity. Their chemical engineering aspects and applications in fermentation processes are considered.     

Plant Taxonomy Today

A computer program for genetic models which has some useful and labour saving features is described. The program allows students with only a rudimentary knowledge of programming to cope easily with complex genetic models. Some applications of the program are discussed.     

Parameterized specification, configuration and execution of data-intensive scientific workflows

Data analysis processes in scientific applications can be expressed as coarse-grain workflows of complex data processing operations with data flow dependencies between them. Performance optimization of these workflows can be viewed as a search for a set of optimal values in a multidimensional parameter space consisting of input performance parameters to the applications that are known to affect their execution times. While some performance parameters such as grouping of workflow components and their mapping to machines do not affect the accuracy of the analysis, others may dictate trading the output quality of individual components (and of the whole workflow) for performance. This paper describes an integrated framework which is capable of supporting performance optimizations along multiple such parameters. Using two real-world applications in the spatial, multidimensional data analysis domain, we present an experimental evaluation of the proposed framework.     

埃博拉病毒疫苗研究进展及相关专利浅析

通过非专利数据库的文献检索,总结了埃博拉病毒（EBOV）研究的最新进展,通过专利文献数据库文献检索分析EBOV疫苗的专利申请基本情况、发展趋势和技术点。结果发现专利申请量与疫情的爆发有一定的相关性;专利申请人多为政府主导的机构或非营利性机构;最新的专利申请均关注GP蛋白对病毒侵染的重要性,针对GP蛋白的抗体和疫苗正在开发中,其中Mapp生物制药公司的产品“ZMapp”作为试验性生物药物目前效果最佳。     

Improved quantitative and qualitative production of single-domain intrabodies mediated by the co-expression of Erv1p sulfhydryl oxidase

Camelidae single domain antibodies (VHHs) have structural and binding features that render them suitable alternatives to conventional IgG antibodies. VHHs are usually easier to produce as recombinant proteins than other antibody fragments. However, for some of the biotechnological applications for which they have been proposed, such as immunochromatography and assisted-crystallography, large amounts of purified antibodies are necessary, whereas some VHH-fusions with common tags such as GFP and SNAP are poorly expressed in the bacterial periplasm. Here we have shown that the co-expression of Erv1p sulfhydryl oxidase resulted in an astonishing yield increase of VHH-SNAP constructs expressed in the bacterial cytoplasm. The resulting recombinant antibodies were also more stable than the antibodies produced using the same plasmid, but in wild-type bacteria. Using this approach, it was possible to obtain tens of milligram of purified fusion antibodies using a basic flask fermentation protocol. Therefore, the described method represents a valid solution to produce inexpensively large amounts of single domain antibodies for in vitro applications and we expect it will be suitable for the production of other antibody fragments.     

Detection of singlet oxygen and its role in dye-sensitized photooxidation in aqueous and micellar solutions

Indirect methods for the detection of singlet oxygen in dye-sensitized photooxidation based on its interception by some singlet oxygen acceptors in aqueous and micellar solutions are discussed. Mechanistic aspects and some applications of a very sensitive method using p-nitrosodimethylaniline in the presence of imidazole (RNO + imidazole method) are also treated. The technique of competition kinetics with a singlet oxygen quencher N-3 which can serve for the determination of the role of singlet oxygen is discussed as well. Such competition with tryptophan and guanosine shows that these substrates react exclusively or predominantly via the singlet oxygen mechanism in the presence of hematoporphyrin as sensitizing dye.     

Novel and Transgenic Food Crops: Overview of Scientific Versus Public Perception

Recombinant DNA technology offers opportunities to develop new products in many different fields, including agriculture and the agro-food area. Transgenic plants with improved agronomic traits currently grow in field trials and a few varieties have already reached the European market. By and large, new technologies raise both concerns and expectations and modern biotechnology is no exception. Indeed, a voluntary moratorium on experiments involving recombinant DNA molecules was called for in 1974. At the present time, although a majority of academic and industrial scientists agree that transgenic food crops pose no risk for the environment or human health, some others believe that certain applications of modern plant biotechnology are hazardous. In particular, deliberate releases of genetically modified plants are regarded as risky. There is also a disparity between expert and lay perception of r-DNA technology applications to food crops, which makes public information a difficult task. This paper aims at exposing these conflicting points of view on the agricultural applications of modern biotechnology. We also propose some recommendations pertaining to public information in Europe. It appears that consensus conferences might be a good approach to stimulate public information and public debate in Europe, although this approach has to be adapted to the cultural context of each country.     

Engineering proteins with tunable thermodynamic and kinetic stabilities

It is widely recognized that enhancement of protein stability is an important biotechnological goal. However, some applications at least, could actually benefit from stability being strongly dependent on a suitable environment variable, in such a way that enhanced stability or decreased stability could be realized as required. In therapeutic applications, for instance, a long shelf-life under storage conditions may be convenient, but a sufficiently fast degradation of the protein after it has performed the planned molecular task in vivo may avoid side effects and toxicity. Undesirable effects associated to high stability are also likely to occur in food-industry applications. Clearly, one fundamental factor involved here is the kinetic stability of the protein, which relates to the time-scale of the irreversible denaturation processes and which is determined to some significant extent by the free-energy barrier for unfolding (the barrier that "separates" the native state from the highly-susceptible-to-irreversible-alterations nonnative states). With an appropriate experimental model, we show that strong environment-dependencies of the thermodynamic and kinetic stabilities can be achieved using robust protein engineering. We use sequence-alignment analysis and simple computational electrostatics to design stabilizing and destabilizing mutations, the latter introducing interactions between like charges which are screened out at high salt. Our design procedures lead naturally to mutating regions which are mostly unstructured in the transition state for unfolding. As a result, the large salt effect on the thermodynamic stability of our consensus plus charge-reversal variant translates into dramatic changes in the time-scale associated to the unfolding barrier: from the order of years at high salt to the order of days at low salt. Certainly, large changes in salt concentration are not expected to occur in biological systems in vivo. Hence, proteins with strong salt-dependencies of the thermodynamic and kinetic stabilities are more likely to be of use in those cases in which high-stability is required only under storage conditions. A plausible scenario is that inclusion of high salt in liquid formulations will contribute to a long protein shelf-life, while the lower salt concentration under the conditions of the application will help prevent the side effects associated with high-stability which may potentially arise in some therapeutic and food-industry applications. From a more general viewpoint, this work shows that consensus engineering and electrostatic engineering can be readily combined and clarifies relevant aspects of the relation between thermodynamic stability and kinetic stability in proteins.