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11.
1 ISO140 0 1认证证书是绿色通行证国际标准化组织于 1987年和 1996年分别发布了ISO90 0 0和ISO140 0 0两大管理体系标准。ISO140 0 0则后来居上 ,其发展势头远远超过了ISO90 0 0。到目前为止 ,在短短的四年多的时间里 ,世界各国取得ISO140 0 1认证的单位已达到 2 0 0 0 0多家 ,我国也有 5 0 0多家取得了ISO140 0 1的认证 ,今后每年将以数倍的速度发展。其原因是 :人们在严酷的现实面前 ,逐渐深刻地认识到对环境的破坏而造成的沉重后果 ,“我们只有一个地球”的说法越来越深入人心。而对环境问题的关注 ,实质上是社会…  相似文献   
12.
Macrocycles constitute an attractive structural class of molecules for targeting biomolecular interfaces with high affinity and specificity. Here, we report systematic studies aimed at exploring the scope and mechanism of a novel chemo‐biosynthetic strategy for generating macrocyclic organo‐peptide hybrids (MOrPHs) through a dual oxime‐/intein‐mediated ligation reaction between a recombinant precursor protein and bifunctional, oxyamino/1,3‐amino‐thiol compounds. An efficient synthetic route was developed to access structurally different synthetic precursors incorporating a 2‐amino‐ mercaptomethyl‐aryl (AMA) moiety previously found to be important for macrocyclization. With these compounds, the impact of the synthetic precursor scaffold and of designed mutations within the genetically encoded precursor peptide sequence on macrocyclization efficiency was investigated. Importantly, the desired MOrPHs were obtained as the only product from all the different synthetic precursors probed in this study and across peptide sequences comprising four to 15 amino acids. Systematic mutagenesis of the “i?1” site at the junction between the target peptide sequence and the intein moiety revealed that the majority of the 20 amino acids are compatible with MOrPH formation; this enables the identification of the most and the least favorable residues for this critical position. Furthermore, interesting trends with respect to the positional effect of conformationally constrained (Pro) and flexible (Gly) residues on the reactivity of randomized hexamer peptide sequences were observed. Finally, mechanistic investigations enabled the relative contributions of the two distinct pathways (side‐chain→C‐end ligation versus C‐end→side‐chain ligation) to the macrocyclization process to be dissected. Altogether, these studies demonstrate the versatility and robustness of the methodology to enable the synthesis and diversification of a new class of organo‐peptide macrocycles and provide valuable structure–reactivity insights to inform the construction of macrocycle libraries through this chemo‐biosynthetic strategy.  相似文献   
13.
14.
Macromers with functional groups that allow for chemical derivatization, polymerization reactions or impart specific physico-chemical properties are functional building blocks for polymeric systems used in different biomedical applications. With this motivation, a series of oligomeric macromers was synthesized by free radical polymerization of maleic anhydride (MA) with N-isopropylacrylamide (NiPAAm) and pentaerythritol diacrylate monostearate (PEDAS). This chemical design provides anhydride groups for effective reactivity of the macromers with amines and other nucleophiles, copolymerized NiPAAm for temperature responsiveness and lipophilic stearate domains for increased hydrogel stability. Macromers were synthesized with different MA co-monomer feeds and oligomeric molecules (Mn below 5000 Da) were obtained with MA contents between 7% and 27% as determined by titration. The fraction of chemically intact anhydrides was calculated to range from 75% to 80%. The ability of the macromers to cross-link di- or oligovalent amines as a function of MA content was investigated rheologically. It was also demonstrated that monovalent amines, e.g. aminofluorescein, could be grafted to the macromer chain utilizing only a fraction of the anhydride functionalities. The derivatized macromers could still participate in cross-linking reactions due to the remaining anhydrides. Temperature sensitivity was shown for aqueous solutions of macromers with fully dissociated anhydride groups. The solutions were additionally responsive to changes in calcium ion concentration and pH. Extracts from macromer cross-linked polyether hydrogels showed no toxicity on L929 fibroblasts.The macromers have perspective as biocompatible cross-linkers for hydrogel fabrication from various biomacromolecules with the opportunity to decorate the gels with monoamine molecules that alter the biological or physico-chemical properties.  相似文献   
15.
P‐Glycoprotein (P‐gp) is an efflux transporter widely expressed at the human blood–brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P‐gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2‐[2‐(2‐methyl‐(11C)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([11C]‐ 5 ); 2‐[2‐(2‐fluoromethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetra‐hydroisoquinoline ([18F]‐ 6 ); and 2‐[2‐(2‐fluoroethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([18F]‐ 7 ), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P‐gp. Methyl derivative [11C]‐ 5 is a potent P‐gp substrate, whereas the corresponding fluoroethyl derivative [18F]‐ 7 is a P‐gp inhibitor. Fluoromethyl compound [18F]‐ 6 is classified as a non‐transported P‐gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [11C]‐ 5 and [18F]‐ 7 , respectively, for in vivo imaging of P‐gp by using PET.  相似文献   
16.
神经酰胺脂质体——含角质层脂质膜的脂质体   总被引:4,自引:0,他引:4  
角质层的渗透屏障大多是由饱和脂质如神经酰胺、胆固醇和游离脂肪酸组成。它是物质交换的有效阻隔并防止皮肤干燥。神经酰胺脂质体(Cerasomes)是一种脂质体,它的膜是由最重要的角质层脂质组成的。神经酰胺脂质体作为类皮肤膜的来源,它能加快受损屏障层的再生、降低皮肤刺激,并且它还提供了将角质层脂质应用于化妆品中简单而有效的途径。  相似文献   
17.
Besides the well-known functions performed by vitamin B12 (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands. Syntheses, spectroscopic analysis of postreaction systems and kinetic investigations of conjugate formation reactions, have been complemented by DFT modelling. The obtained results showed that ligand charge, geometry and electron affinity may have a significant impact on carrier binding and release leading to the activation of the Pd(II) complex. This provides a rationale to expect that with appropriate composition of the coordination sphere, it will be possible to extend the spectrum of less toxic inorganic chemotherapeutics.  相似文献   
18.
An experimental investigation of boiling phenomena in inductively heated particle beds has been performed. The major aim of these experiments is to provide data for validating numerical codes used in reactor safety. The experiments can be divided in three parts: boiling experiments, dryout experiments and quenching experiments. In boiling experiments, the pressure gradients have been measured along the bed height for different flow modes, different heat inputs and different system pressures. In dryout experiments, the minimum heat input has been determined for which the particle bed starts to superheat significantly above the saturation temperature. The final test series deals with the cool down behaviour of strongly superheated particles by flooding them with cold water. The initial temperatures ranged from 200 up to 900 °C in top-quenching experiments and from 230 up to 450 °C in bottom-quenching experiments. All experiments were performed with pre-oxidised stainless steel balls of 6 and 3 mm diameter in a cylindrical crucible. The bed height was 640 mm and the bed diameter was 125 mm for boiling and dryout experiments, respectively 150 mm for quenching experiments. The experimental results are compared with various available dryout models.  相似文献   
19.
A tendency towards growing requirements for the inspection of austenitic piping can be observed in several countries. In Germany the revised KTA rule demands the UT inspection of austenitic and dissimilar metal welds in piping with diameters of 200 mm or more.On the basis of experience gained from austenitic piping with integranular stress corrosion cracking (IGSCC), longitudinal waves and mode conversion techniques are used. Depending on the geometry, material and grain orientation, spurious signals can be observed which require additional evaluation or analysis measurements.A promising new technique is based on horizontally polarized shear (SH) waves generated by electromagnetic acoustic transducers (EMATs). Investigations in the laboratory and field inspections showed that SH waves are well suited for the detection of longitudinal flaws, especially where the weld can be examined from one side only.For the complete solution of a given inspection problem SH waves can be combined with well-known standard techniques in order to provide redundant information for the characterization and sizing of indications.The investigation of possibilities of SH waves showed that the problem of cast austenitic steel inspection might not be solved using this technique. However, measurements using low frequency UT transducers showed promising results.  相似文献   
20.
We superimpose weaving patterns on planar line arrangements, and we face the question when they can be realized by lines in 3-space. Using the combinatorial type of the given lines in the plane we derive a class of nonrealizable weavings.  相似文献   
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