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Custom-designed DNA arrays offer the possibility of simultaneously monitoring thousands of hybridization reactions. These arrays show great potential for many medical and scientific applications, such as polymorphism analysis and genotyping. Relatively high costs are associated with the need to specifically design and synthesize problem-specific arrays. Recently, an alternative approach was suggested that utilizes fixed, universal arrays. This approach presents an interesting design problem-the arrays should contain as many probes as possible, while minimizing experimental errors caused by cross-hybridization. We use a simple thermodynamic model to cast this design problem in a formal mathematical framework. Employing new combinatorial ideas, we derive an efficient construction for the design problem and prove that our construction is near-optimal. 相似文献
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Although new detection screening methods must still be developed, the actual main limitation in combinatorial chemistry seems to be the diversity of ligands that can be generated in terms of real structural and chemical diversity. Thus, there is a strong interest for the development of different strategies for the parallel or combinatorial synthesis of ligands. We report here a selection of recent attempts proposing 'open' approaches able to increase the diversity of molecular architecture truly accessible via parallel or combinatorial processes. 相似文献
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Over the last 20 years, there has been a growing requirement by governments around the world for organisations to adopt more sustainable practices. Wastewater treatment is no exception, with many currently used systems requiring large capital investment, land area and power consumption. High rate algal ponds offer a sustainable, efficient and lower cost option to the systems currently in use. They are shallow, mixed lagoon based systems, which aim to maximise wastewater treatment by creating optimal conditions for algal growth and oxygen production—the key processes which remove nitrogen and organic waste in HRAP systems. This design means they can treat wastewater to an acceptable quality within a fifth of time of other lagoon systems while using 50% less surface area. This smaller land requirement decreases both the construction costs and evaporative water losses, making larger volumes of treated water available for beneficial reuse. They are ideal for rural, peri-urban and remote communities as they require minimum power and little on-site management. This review will address the history of and current trends in high rate algal pond development and application; a comparison of their performance with other systems when treating various wastewaters; and discuss their potential for production of added-value products. Finally, the review will consider areas requiring further research. 相似文献
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A series of novel, functionalized catecholamines (congeners) has been synthesized in which, formalistically, the N-isopropyl group of isoproterenol has been extended by a linear alkyl chain of varying length, terminated by a carboxyl group. Model amide derivatives have also been prepared in order to optimize the biological activity of these derivatives and also to aid in the design of appropriate peptides for the synthesis of conjugates. As a result of these studies, a series of amino acid and monodisperse peptide carriers, containing p-aminophenylalanine as the point of attachment for the drug, was prepared, together with the corresponding conjugates. In vitro and in vivo evaluation of the congeners, model amides, and conjugates has demonstrated that the biological activity of these derivatives is extremely sensitive to structural modifications at a point far-removed from the pharmacophore, in both the congener amide and conjugate series. A number of the model amides and conjugates have proven to be highly active when tested in both in vitro and in vivo test systems. The implications of these results in terms of a novel structure–activity approach to drug design are discussed. 相似文献
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Axonal regeneration is inhibited by a plethora of different mechanisms in the adult central nervous system (CNS). While neurotrophic factors have been shown to stimulate axonal growth in numerous animal models of nervous system injury, a lack of suitable growth substrates, an insufficient activation of neuron-intrinsic regenerative programs, and extracellular inhibitors of regeneration limit the efficacy of neurotrophic factor delivery for anatomical and functional recovery after spinal cord injury. Thus, growth-stimulating factors will likely have to be combined with other treatment approaches to tap into the full potential of growth factor therapy for axonal regeneration. In addition, the temporal and spatial distribution of growth factors have to be tightly controlled to achieve biologically active concentrations, to allow for the chemotropic guidance of axons, and to prevent adverse effects related to the widespread distribution of neurotrophic factors. Here, we will review the rationale for combinatorial treatments in axonal regeneration and summarize some recent progress in promoting axonal regeneration in the injured CNS using such approaches. 相似文献
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New approaches for cell-specific targeting: identification of cell-selective peptides from combinatorial libraries 总被引:3,自引:0,他引:3
Brown KC 《Current opinion in chemical biology》2000,4(1):16-21
Peptides that recognize specific cell types promise to be valuable tools both in research and clinical applications. Cell-specific peptides can be useful as drug delivery vehicles, diagnostic agents, affinity reagents for cell purification, gene therapy delivery agents, and research tools to probe the nature of a cell's surface. Recently, cell-specific targeting-peptides have been identified by phage-display selections against purified cell-surface markers, whole cells in tissue culture, and even tissues within live animals. These methods for identifying cell-targeting peptides will certainly increase the tools available to the scientist for cell-specific targeting. 相似文献
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Proteins rarely function in isolation but they form part of complex networks of interactions with other proteins within or among cells. The importance of a particular protein for cell viability is directly dependent upon the number of interactions where it participates and the function it performs: the larger the number of interactions of a protein the greater its functional importance is for the cell. With the advent of genome sequencing and "omics" technologies it became feasible conducting large-scale searches for protein interacting partners. Unfortunately, the accuracy of such analyses has been underwhelming owing to methodological limitations and to the inherent complexity of protein interactions. In addition to these experimental approaches, many computational methods have been developed to identify protein-protein interactions by assuming that interacting proteins coevolve resulting from the coadaptation dynamics between the amino acids of their interacting faces. We review the main technological advances made in the field of interactomics and discuss the feasibility of computational methods to identify protein-protein interactions based on the estimation of coevolution. As proof-of-concept, we present a classical case study: the interactions of cell surface proteins (receptors) and their ligands. Finally, we take this discussion one step forward to include interactions between organisms and species to understand the generation of biological complexity. Development of technologies for accurate detection of protein-protein interactions may shed light on processes that go from the fine-tuning of pathways and metabolic networks to the emergence of biological complexity. 相似文献
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Evans MR Norris KJ Benton TG 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2012,367(1586):163-169
The world is experiencing significant, largely anthropogenically induced, environmental change. This will impact on the biological world and we need to be able to forecast its effects. In order to produce such forecasts, ecology needs to become more predictive--to develop the ability to understand how ecological systems will behave in future, changed, conditions. Further development of process-based models is required to allow such predictions to be made. Critical to the development of such models will be achieving a balance between the brute-force approach that naively attempts to include everything, and over simplification that throws out important heterogeneities at various levels. Central to this will be the recognition that individuals are the elementary particles of all ecological systems. As such it will be necessary to understand the effect of evolution on ecological systems, particularly when exposed to environmental change. However, insights from evolutionary biology will help the development of models even when data may be sparse. Process-based models are more common, and are used for forecasting, in other disciplines, e.g. climatology and molecular systems biology. Tools and techniques developed in these endeavours can be appropriated into ecological modelling, but it will also be necessary to develop the science of ecoinformatics along with approaches specific to ecological problems. The impetus for this effort should come from the demand coming from society to understand the effects of environmental change on the world and what might be performed to mitigate or adapt to them. 相似文献
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The efficiency of existing combinatorial biological library methods has been moderate in terms of the success rates, the affinities of the ligands selected and the time and effort involved in trying to optimize the initial leads. Although mimicking natural evolution, existing strategies take little notice of the importance of recombination within a selected population to generate increased diversity. We present an overview of our recent progress which has resulted in the successful development of such a strategy, which we designate cosmix-plexing. We incorporate recombination as a central feature in obtaining high success rates and high affinities, even for short monomer peptides, in a very short time. The method uses type II restriction enzymes to re-assort small hypervariable DNA cassettes from an intermediate pre-selected population (e.g. from a phagemid display library), while maintaining the original open-reading frame. Since, in the naive library, each cassette contains all possible combinations of the polypeptide sequences it encodes, much longer regions can be optimized than was possible with methods which depend on a simple selection from the naive library. Short peptides can now be rapidly selected, which exhibit the same, or higher, specificity and affinity for a defined target molecule, than (say) an antibody or even the natural ligand. 相似文献
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Nonpeptide compounds that mimic bioactive peptides are desirable for a number of clinical indications. We report a new practical method for the design of scaffolds exhibiting drug-like properties that are suitable for the display of peptide pharmacophores. The synthesis of various synthons of 7'-hydroxy-2',3'-dihydro-1'H,2H,5H-spiro[imidazolidine-4,4'-quinoline]-2,5-dione (1) and methods for the introduction of several mimics of amino acid side-chains are described. This method is exemplified by derivatives that show agonist activity for the somatostatin type 2 receptor. 相似文献
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Osteoarthritis (OA) is a multi-factor disorder of sinovial joints, which characterized by escalated degeneration and loss
of articular cartilage. Treatment of OA is a critical unmet need in medicine for regeneration of damaged articular cartilage
in elderly. On the other hand, lubricin, a glycoprotein specifically synthesized by chondrocytes located at the surface of
articular cartilage, has been shown to provide boundary lubrication of congruent articular surfaces under conditions of high
contact pressure and near zero sliding speed. Lubrication of these surfaces is critical to normal joint function, while different
gene expressions of lubricin had been found in the synovium of rheumatoid arthritis (RA) and OA. Moreover, mutations or lacking
of lubricin gene have been shown to link to the joint disease such as camptodactyly-arthropathy-coxa vara-pericarditis syndrome
(CACP), synovial hyperplasia and failure of joint function, suggesting an important role of lubricin in the pathogenesis of
these joint disease. Recent studies demonstrate that administration with recombinant lubricin in the joint cavity would be
effective in the prevention of cartilage degeneration in animal OA models. Therefore, a treatment with lubricin which would
protect cartilage in vivo would be desirable. This article reviews recent findings with regard to the possible role of lubricin
in the progression of OA, and further discusses lubricin as a novel potential biotherapeutic approaches for the treatment
of OA. 相似文献
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Felton LA 《AAPS PharmSciTech》2007,8(4):258-266
Polymeric film coatings have been applied to solid substrates for decorative, protective, and functional purposes. Irrespective of the reasons for coating, certain properties of the polymer films may be determined as a method to evaluate coating formulations, substrate variables, and processing conditions. This article describes experimental techniques to assess various properties of both free and applied films, including water vapor and oxygen permeability, as well as thermal, mechanical, and adhesive characteristics. Methods to investigate interfacial interactions are also presented. 相似文献
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Trehalose production: exploiting novel approaches 总被引:28,自引:0,他引:28
Trehalose (alpha-D-glucopyranosyl alpha-D-glucopyranoside) is a unique sugar capable of protecting biomolecules against environmental stress. It is a stable, colorless, odor-free and non-reducing disaccharide, and is widespread in nature. Trehalose has a key role in the survival of some plants and insects, termed anhydrobionts, in harsh environments, even when most of their water body is removed. The properties of these types of organisms drove attention towards the study of trehalose. Since then, it proved to be an active stabilizer of enzymes, proteins, biomasses, pharmaceutical preparations and even organs for transplantation. Recently, trehalose has been accepted as a safe food ingredient by the European regulation system following approval by the US Food and Drug Administration. The wide range of applications of this sugar has increased the interest of many research groups into the development of novel and economically feasible production systems. This article provides a comprehensive review of the current achievements in the biotechnological production of trehalose. 相似文献