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1.
Athina Dimopoulou Stella Manta Vanessa Parmenopoulou Petros Gkizis Evdoxia Coutouli-Argyropoulou Dominique Schols 《Nucleosides, nucleotides & nucleic acids》2015,34(4):289-308
We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a–e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a–e and thioguanine 4a–e nucleosides, while their N-7 substituted congeners 10a–e and 7a–e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a–e, 5a–e, 8a–e, and 11a–e were evaluated for their cytostatic activity in three different tumor cell proliferative assays. 相似文献
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Gourbatsi E Al-Fageeh MB Marchant RJ Scott SJ Underhill MF Smales CM 《Molecular biotechnology》2006,33(1):1-11
The generation of cell lines stably expressing recombinant material is a lengthy process and there has thus been much interest
in the use of transient expression systems to rapidly produce recombinant material. To achieve this, the DNA of interest must
be delivered into the nucleus of the target cell. The mechanisms by which this process occurs are poorly understood and the
efficiency of various methods differs widely. Recently, nuclear localization signals (NLSs) have been investigated to target
entry of DNA into the nucleus of mammalian cells. We have used NLSs from the SV40 and Tat antigens mixed with our model luciferase
reporter gene plasmid for the transfection of Chinese hamster ovary (CHO) cells using calcium phosphate and FuGNE 6 transfection
technology. The nocovalent complexation of NLSs with plasmid DNA before calcium phosphate-mediated transfection resulted in
enhanced reporter gene expression with increasing ratios of NLS to plasmid until reaching a mximum. At higher ratios than
maximum expression, the expression levels decreased. On the other hand, when using FuGENE 6 reagent NLSs did not enhance reporter
gene expression. Cell cycle arrest in G2/M phase obliterated the effect of the NLS on reporter gene expression when using the calcium phosphate transfection method. 相似文献
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Eleni Karali Beat Brunner Ruth Doherty Anna M. Hersperger Mark D. A. Rounsevell 《Human ecology: an interdisciplinary journal》2013,41(6):915-926
Identifying and interpreting the heterogeneity of farmer behaviour is becoming increasingly important in support of policy- and decision-making goals. This paper explores whether observed differences in farming practices can be interpreted from the heterogeneity of farmer behaviour. Farmer attitudes and objectives were analysed using a combination of principal components and cluster analysis applied to responses to statements in a telephone-based survey. Respondents were classified into four profiles; business-oriented, lifestylers, multifunctionalists and traditionalists. Each profile differed in terms of farm management practices, the amount of land farmers either managed or owned, the existence of successors and the importance placed on household members in providing information. The results suggest that knowledge of farmer behavioural profiles could support more targeted policy development that accounts for alternative farmer goals. However, similarities were also found between the profiles, suggesting that farmer behaviour would be better interpreted as a dynamic set of identities, rather than as static profiles. 相似文献
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Objectives
There are a number of blockbuster monoclonal antibodies on the market used for the treatment of a variety of diseases. Although the formulation of many antibodies is achieved in ‘platform’ formulations, some are so difficult to formulate that it can result in an inability to develop a finished drug product. Further, a large number of antibody-inspired or-based molecules are now being developed and assessed for biotherapeutic purposes and less is understood around the required active protein drug concentrations, excipients and additives required in final product formulations.Results
We investigated the effect of formulation variables (pH, buffer composition, glycine and NaCl concentration, time and temperature of accelerated stability studies) on antibody solubility/aggregation and activity using a Plackett–Burman Experimental Design approach. We then used the findings from this study and applied these to the formulation of a single chain variable fragment (ScFv) molecule. Our data shows that prediction of ScFc stability from a model monoclonal antibody could be achieved although further formulation optimization was required. Mass spectrometry analysis confirmed changes to the mass and hence authenticity of both the model antibody and ScFv under formulation conditions that did not provide appropriate conditions for protection of the molecules.Conclusions
The role of the different formulation conditions on maintaining protein integrity is described and using mass spectrometry shows that protein integrity is compromised under particular conditions. The implications for predicting successful formulations for protein molecules is discussed and how antibody formulations could be used to predict formulation components for novel antibody based molecules.6.
Plant biotechnology relies heavily on the genetic manipulation of crops. Almost invariantly, the gene of interest is expressed in a constitutive fashion, although this may not be strictly necessary for several applications. Currently, there are several regulatable expression systems for the temporal, spatial and quantitative control of transgene activity. These molecular switches are based on components derived from different organisms, which range from viruses to higher eukaryotes. Many inducible systems have been designed for fundamental and applied research and since their initial development, they have become increasingly popular in plant molecular biology.This review covers a broad number of inducible expression systems examining their properties and relevance for plant biotechnology in its various guises, from molecular breeding to pharmaceutical and industrial applications. For each system, we examine some advantages and limitations, also in relation to the strategy on which they rely. Besides being necessary to control useful genes that may negatively affect crop yield and quality, we discuss that inducible systems can be also used to increase public acceptance of GMOs, reducing some of the most common concerns. Finally, we suggest some directions and future developments for their further diffusion in agriculture and biotechnology. 相似文献
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A protected trihydroxyindolizidine 3-carboxylate was prepared by a 6-endo epoxide cleavage, which in turn was intermediately formed from the hetero-Diels-Alder adduct of ethyl 2-nitrosoacrylate to a D-ribose-derived exo-glycal. 相似文献
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The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer 下载免费PDF全文
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M. Žužek J. Friedrich B. Cestnik A. Karalič A. Cimerman 《Biotechnology Techniques》1996,10(12):991-996
Summary During the study of mevinolin biosynthesis by Aspergillus terreus ATCC 20542, 10 different medium components were selected for medium optimization. A new optimization method based on genetic algorithms and inductive learning was used for experimental design. For better efficiency the method was supported by a model, constructed with machine learning method, to predict the productivity. In four generations of fermentation experiments the productivity increased nearly three times. 相似文献
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