971 resultados para Absolute generality


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Thesis (doctoral)--Rijks-Universiteit te Leiden.

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Thesis (doctoral)--Universiteit van Amsterdam.

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Thesis (doctoral)--

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Azedaralide, a potentially advanced intermediate for the total synthesis of various tetranortriterpenes, was constructed utilising the Fernandez-Mateos protocol and assigned both relative and absolute stereochemistries. Both asymmetric aldol and classical chiral resolution attempts failed to deliver pure enantiomers whereas preparative chiral chromatography resolved racemic azedaralide with ease. (c) 2006 Elsevier Ltd. All rights reserved.

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SFTI-1 is a small cyclic peptide from sunflower seeds that is one of the most potent trypsin inhibitors of any naturally occurring peptide and is related to the Bowman-Birk family of inhibitors (BBIs). BBIs are involved in the defense mechanisms of plants and also have potential as cancer chemopreventive agents. At only 14 amino acids in size, SFTI-1 is thought to be a highly optimized scaffold of the BBI active site region, and thus it is of interest to examine its important structural and functional features. In this study, a suite of 12 alanine mutants of SFTI-1 has been synthesized, and their structures and activities have been determined. SFTI-1 incorporates a binding loop that is clasped together with a disulfide bond and a secondary peptide loop making up the circular backbone. We show here that the secondary loop stabilizes the binding loop to the consequences of sequence variations. In particular, full-length BBIs have a conserved cis-proline that has been shown previously to be required for well defined structure and potent activity, but we show here that the SFTI-1 scaffold can accommodate mutation of this residue and still have a well defined native-like conformation and nanomolar activity in inhibiting trypsin. Among the Ala mutants, the most significant structural perturbation occurred when Asp(14) was mutated, and it appears that this residue is important in stabilizing the trans peptide bond preceding Pro(13) and is thus a key residue in maintaining the highly constrained structure of SFTI-1. This aspartic acid residue is thought to be involved in the cyclization mechanism associated with excision of SFTI-1 from its 58-amino acid precursor. Overall, this mutational analysis of SFTI-1 clearly defines the optimized nature of the SFTI-1 scaffold and demonstrates the importance of the secondary loop in maintaining the active conformation of the binding loop.

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Absolute calibration relates the measured (arbitrary) intensity to the differential scattering cross section of the sample, which contains all of the quantitative information specific to the material. The importance of absolute calibration in small-angle scattering experiments has long been recognized. This work details the absolute calibration procedure of a small-angle X-ray scattering instrument from Bruker AXS. The absolute calibration presented here was achieved by using a number of different types of primary and secondary standards. The samples were: a glassy carbon specimen, which had been independently calibrated from neutron radiation; a range of pure liquids, which can be used as primary standards as their differential scattering cross section is directly related to their isothermal compressibility; and a suspension of monodisperse silica particles for which the differential scattering cross section is obtained from Porod's law. Good agreement was obtained between the different standard samples, provided that care was taken to obtain significant signal averaging and all sources of background scattering were accounted for. The specimen best suited for routine calibration was the glassy carbon sample, due to its relatively intense scattering and stability over time; however, initial calibration from a primary source is necessary. Pure liquids can be used as primary calibration standards, but the measurements take significantly longer and are, therefore, less suited for frequent use.

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Document ranking is an important process in information retrieval (IR). It presents retrieved documents in an order of their estimated degrees of relevance to query. Traditional document ranking methods are mostly based on the similarity computations between documents and query. In this paper we argue that the similarity-based document ranking is insufficient in some cases. There are two reasons. Firstly it is about the increased information variety. There are far too many different types documents available now for user to search. The second is about the users variety. In many cases user may want to retrieve documents that are not only similar but also general or broad regarding a certain topic. This is particularly the case in some domains such as bio-medical IR. In this paper we propose a novel approach to re-rank the retrieved documents by incorporating the similarity with their generality. By an ontology-based analysis on the semantic cohesion of text, document generality can be quantified. The retrieved documents are then re-ranked by their combined scores of similarity and the closeness of documents’ generality to the query’s. Our experiments have shown an encouraging performance on a large bio-medical document collection, OHSUMED, containing 348,566 medical journal references and 101 test queries.

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We propose a self-reference multiplexed fibre interferometer (MFI) by using a tunable laser and fibre Bragg grating (FBG). The optical measurement system multiplexes two Michelson fibre interferometers with shared optical path in the main part of optical system. One fibre optic interferometer is used as a reference interferometer to monitor and control the high accuracy of the measurement system under environmental perturbations. The other is used as a measurement interferometer to obtain information from the target. An active phase tracking homodyne (APTH) technique is applied for signal processing to achieve high resolution. MFI can be utilised for high precision absolute displacement measurement with different combination of wavelengths from the tuneable laser. By means of Wavelength-Division-Multiplexing (WDM) technique, MFI is also capable of realising on-line surface measurement, in which traditional stylus scanning is replaced by spatial light-wave scanning so as to greatly improve the measurement speed and robustness.

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We propose a self-reference multiplexed fibre interferometer (MFI) by using a tunable laser and fibre Bragg grating (FBG). The optical measurement system multiplexes two Michelson fibre interferometers with shared optical path in the main part of optical system. One fibre optic interferometer is used as a reference interferometer to monitor and control the high accuracy of the measurement system under environmental perturbations. The other is used as a measurement interferometer to obtain information from the target. An active phase tracking homodyne (APTH) technique is applied for signal processing to achieve high resolution. MFI can be utilised for high precision absolute displacement measurement with different combination of wavelengths from the tuneable laser. By means of Wavelength-Division-Multiplexing (WDM) technique, MFI is also capable of realising on-line surface measurement, in which traditional stylus scanning is replaced by spatial light-wave scanning so as to greatly improve the measurement speed and robustness. © 2004 Optical Society of America.

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As the world’s natural resources dwindle and critical levels of environmental pollution are approached, sustainability becomes a key issue for governments, organisations and individuals. With the consequences of such an issue in mind, this paper introduces a unifying approach to measure the sustainability performance of socio-economic systems based on the interplay between two key variables: essentiality of consumption and environmental impact. This measure attributes to every system a ‘fitness’ value i.e. a quantity that reflects its ability to remain resilient/healthy by avoiding ecological, social and economic collapse as it consumes the available resources. This new measure is tested on a system where there is a limited supply of resources and four basic consumption types. The analysis has theoretical implications as well as practical importance as it can help countries, organisations or even individuals, in finding better ways to measure sustainability performance.

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Pahayokolides A-D are cytotoxic cyclic polypeptides produced by the freshwater cyanobacterium Lyngbya sp. strain 15-2 that possess an unusual β-amino acid, 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid (Athmu). The absolute configuration of pahayokolides A-D was determined using advanced Marfey’s method. It was also confirmed that a pendant N-acetyl- N-methyl leucine moiety in pahayokolide A was absent in pahayokolides B and pahayokolides C-D were conformers of pahayokolide A. Feeding experiments indicated that the biosynthesis of the Athmu sidechain arises from leucine or α-ketoisovalerate, however could not be further extended by three rounds of condensation with malonate units. Putative four peptide and one unique polyketide synthetases in Lyngbya sp. strain 15-2 were identified by using a PCR method and degenerate primers derived from conserved core sequences of known NRPSs and PKSs. Identification of one unique KS domain conflicted with the logic rule that the long side chain of Athmu was assembled by three rounds of ketide extensions if PKSs were involved. A gene cluster (pah) encoding a peptide synthetase putatively producing pahayokolide was cloned, partially sequenced and characterized. Seven modules of the non-ribosomal peptide synthetase (NRPS) were identified. Ten additional opening reading frames (ORFs) were found, responsible for peptide resistance, transport and degradation. Although the predicted substrate specificities of NRPS agreed with the structure of pahayokolide A partially, the disagreement could be explained. However, no PKS gene was found in the pah gene cluster.