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61.
The aim of this study was to elucidate the possible causes of elevated low-density lipoprotein (LDL)-cholesterol levels in transplanted patients treated with the immunosuppressant drug, cyclosporine. HepG2 cells, from a well-differentiated cell-line of hepatoma cells, were cultured and used as a model for in vitro hepatocytic LDL uptake. Different concentrations of cyclosporine, which were within the range of concentrations found in humans treated with cyclosporine, were added to tissue culture medium together with 125I-LDL. The results showed that cyclosporine reduced LDL uptake and degradation in HepG2 cells by about 25%. The cells were also pretreated with cyclosporine for 1 to 24 hours and then incubated with new medium containing labeled LDL for 2 hours at 4 degrees C in an LDL-binding assay. The data showed that cyclosporine reduced the subsequent LDL binding. Cyclosporine has no toxic effects on HepG2 cells, as shown by unchanged growth capacity of the cells. By means of a 50-fold excess of unlabeled LDL, a monoclonal anti-LDL receptor antibody, and dextran sulfate, we also evaluated if this inhibition of LDL binding occurred through the LDL receptor-mediated pathway, through non-LDL receptor-mediated pathways, or through both. The results show that cyclosporine reduces LDL binding and uptake by mainly inhibiting the LDL receptor-mediated pathway. We also studied the effect of the LDL-cyclosporine complex on the binding of labelled LDL. The presence of cyclosporine in the LDL particle does not influence the binding behaviour of LDL to its receptor. We also found that cyclosporine reduces the expression of the LDL receptor messenger RNA (mRNA) by about 40%. Thus, the interpretation of this study is that cyclosporine can cause an increase in LDL-cholesterol in the plasma of transplantation patients by reducing the catabolism of LDL in the liver by inhibiting mainly the LDL receptor-mediated catabolism through an effect on LDL receptor synthesis.  相似文献   
62.
Materials eliciting increased tongue flicking and prey attack in garter snakes were isolated from both earthworm and fish prey. New extraction methods based on chloroform-methanol mixtures are valuable adjuncts to the more typical aqueous preparations. Both high- and low-molecular weight components from earthworms and fish were active. The similarity between the active chemicals in these two classes of prey was established using several methods of analysis. These included chromatography, carbohydrate and amino acid analyses, and nuclear magnetic resonance.  相似文献   
63.
BB rats and nonobese diabetic (NOD) mice spontaneously develop autoimmune insulin dependent diabetes and serve as models for human type I diabetes. During progression of the disease the cytokine pattern elaborated by islet infiltrating immune cells shifts from a Th2 or Th0 toward Th1 type. Only the latter is associated with "destructive" insulitis. We discuss here attempts to modulate disease progression by targeting the gut immune system with bacterial immunostimulants. Oral dosing of diabetes prone BB rats with lipopolysaccharide (LPS) or the Escherichia coli extract OM-89 lead to a Th2-shift of pancreatic mRNA expression. In vitro studies showed that repeated exposure toward LPS or OM-89 lead to downregulation of proinflammatory macrophage responses. In the NOD mouse, repeated oral dosing of OM-89 caused a Th2 shift in the gut cytokine gene expression, probably because of desensitization of macrophages and other antigen presenting cells. Concomitantly, diabetes prevention by oral insulin was improved. In conclusion, oral dosing with bacterial immunostimulants dampens Th1 type immune reactivities of the gut immune system and thereby promotes oral tolerance mechanisms. Downregulation of proinflammatory immune reactivities by repeated exposure to bacterial stimulants requires intact desensitization mechanisms in macrophages or other antigen presenting cells.  相似文献   
64.
This paper presents an ontology-driven approach for spatial database enrichment in support of map generalisation. Ontology-driven spatial database enrichment is a promising means to provide better transparency, flexibility and reusability in comparison to purely algorithmic approaches. Geographic concepts manifested in spatial patterns are formalised by means of ontologies that are used to trigger appropriate low level pattern recognition techniques. The paper focuses on inference in the presence of vagueness, which is common in definitions of spatial phenomena, and on the influence of the complexity of spatial measures on classification accuracy. The concept of the English terraced house serves as an example to demonstrate how geographic concepts can be modelled in an ontology for spatial database enrichment. Owing to their good integration into ontologies, and their ability to deal with vague definitions, supervised Bayesian inference is used for inferring complex concepts. The approach is validated in experiments using large vector datasets representing buildings of four different cities. We compare classification results obtained with the proposed approach to results produced by a more traditional ontology approach. The proposed approach performed considerably better in comparison to the traditional ontology approach. Besides clarifying the benefits of using ontologies in spatial database enrichment, our research demonstrates that Bayesian networks are a suitable method to integrate vague knowledge about conceptualisations in cartography and GIScience.  相似文献   
65.
Three populations of the water snake,Natrix s. sipedon, were tested for their responses to surface water extracts prepared from various prey species. It was clearly shown that these snakes can distinguish between different prey genera on the basis of chemical cues alone. Adult snakes caught at a fish hatchery where goldfish (Carassius auratus) were abundant responded most to goldfish extract, as did laboratory-born snakes reared on goldfish for one year. However, snakes caught in a relatively undisturbed mountain stream environment and naive young born to a mountain female responded more to the extracts of various sympatric-mountain fish and amphibians. The evidence indicates that newborn snakes have genetic predispositions for sympatric species of the classes of prey normally eaten. These preferences can be enhanced or inhibited during ontogeny.  相似文献   
66.
67.
2‐Methyltetrahydrothiophen‐3‐one ( 3 ) is a volatile compound that plays an important role especially in food and flavour chemistry because it contributes to the aroma of several foodstuffs including wine. Although 3 can be formed by chemical reactions during food preparation, it is also produced by microorganisms. Recent studies with yeasts showed that methionine ( 1 ) is a potential precursor of 3 , but the mechanism of the transformation is unknown. The biosynthetic pathway leading to 3 in the bacterium Chitinophaga Fx7914 was probed. Extensive feeding experiments with differently labelled precursors by using liquid cultures of Chitinophaga Fx7914 were performed. The volatiles released by the bacterium were collected by using a closed loop stripping apparatus (CLSA) and analysed by GC–MS. The observed incorporation pattern of the precursors into 3 led to the elucidation of the biosynthetic pathway. One part of the compound 2 originates from homocysteine ( 15 ), which is transformed into 3‐mercaptopropanal ( 17 ). The second biosynthetic building block is pyruvate ( 14 ). An acyloin‐forming reaction furnishes the key intermediate 21 , which cyclises intramolecularly to a diol. Dehydration followed by tautomerisation lead to the cyclic ketone 3 , which is produced by the bacterium in racemic form.  相似文献   
68.
69.
Atom interferometry represents a quantum leap in the technology for the ultra-precise monitoring of accelerations and rotations and, therefore, for the science that relies on these quantities. These sensors evolved from a new kind of optics based on matter-waves rather than light-waves and might result in an advancement of the fundamental detection limits by several orders of magnitude. This paper describes the current status of the Space Atom Interferometer project (SAI), funded by the European Space Agency. In a multi-pronged approach, SAI aims to investigate both experimentally and theoretically the various aspects of placing atom interferometers in space: the equipment needs, the realistically expected performance limits and potential scientific applications in a micro-gravity environment considering all aspects of quantum, relativistic and metrological sciences. A drop-tower compatible atom interferometry acceleration sensor prototype has been designed, and the manufacturing of its subsystems has been started. A compact modular laser system for cooling and trapping rubidium atoms has been assembled. A compact Raman laser module, featuring outstandingly low phase noise, has been realized. Possible schemes to implement coherent atomic sources in the atom interferometer have been experimentally demonstrated.  相似文献   
70.
Bulk and surface distributions of molecular orientation in injection‐molded plaques of thermotropic liquid crystalline polymers (TLCPs) have been studied using a combination of techniques, coordinated with process simulations using the Larson‐Doi “polydomain” model. Wide‐angle X‐ray scattering was used to map out the bulk orientation distribution. Fourier Transform Infrared Attenuated Total Reflectance (FTIR‐ATR) and Near‐Edge X‐ray Absorption Fine Structure (NEXAFS) were utilized to probe the molecular orientation states to within about ~5 μm and ~2 nm, respectively, of the sample surface. These noninvasive, surface‐sensitive techniques yield reasonable self‐consistency, providing complementary validation of the robustness of these methods. An analogy between Larson‐Doi and fiber orientation models has allowed the first simulations of TLCP injection molding. The simulations capture many fine details in the bulk orientation distribution across the sample plaque. Direct simulation of surface orientation at the level probed by FTIR‐ATR and NEXAFS was not possible due to the limited spatial resolution of the simulations. However, simulation results extracted from the shear‐dominant skin region are found to provide a qualitatively accurate indicator of surface orientation. Finally, simulations capture the relation between bulk and surface orientation states across the different regions of the sample plaque. POLYM. ENG. SCI., 50:1864–1877, 2010. © 2010 Society of Plastics Engineers  相似文献   
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