教学质量监控体系的建立与实践

21世纪高等教育面临着知识经济的严峻挑战 ,这种挑战归根到底体现在对高等教育的质量要求上。2 1世纪中国能否实现文化复兴、民族腾飞和国家昌盛 ,能否跻身于世界强国之林 ,关键取决于教育 ,特别是高等教育所培养的人才质量。所以 ,提高教育质量 ,不仅是高等教育自身发展的生命     

The evaluation of three dimensional image distortion of helical scanning CT

We developed a computer algorithm to simulate distortion in the three-dimensional (3D) displays obtained by helical scanning. The algorithm constitutes calculation of the image profile in the longitudinal direction, which is assumed to be a convolution of the object function with the slice sensitivity profile (SSP) of helical scanning. Experiments were performed to examine the algorithm for its validity with the use of a K2HPO4 phantom. Simulated results and measurements was in a good agreement. The distortion was investigated by the computer simulation. The model simulated was a high density object (Ol) surrounded by low density tissue (Os). The helical interpolation used was 360-degree linear interpolation. Two parameters were defined: delta Lz, which is the difference in length between the 3D image and the actual object Ol in the longitudinal direction, and the cut level index (CLI), which is defined as CLI = (Cut Level CT Number-CT Number of Os)/(CT Number of OI-CT Number of Os). We found that magnitude of delta Lz increased depending on the table feed distance per 360-degree scan (Dt). When Ol was twice as long as Dt, delta Lz directly depended on CLI, but was independent of Ol length. When Ol length was longer than Dt, delta Lz was shown to be 0 at CLI not equal to 0.5 at every Dt. When Ol was shorter than Dt, delta Lz decreased remarkably depending on the length of Ol in higher CLI. The simulations, with the use of a newly developed algorithm, were demonstrated to be useful for evaluating the amount of distortion and for better understanding the characteristics of 3D displays of helical scanning.     

Creation and functional screening of a multi-use peptide library

Studies of functional interactions between transmembrane proteins such as G-protein-coupled receptors and ligands would benefit from the ability to utilize synthetic molecule libraries. This is realized here by the construction and application of a multi-use combinatorial peptide library (MUPL). Peptides are liberated from their supports in a dry state so that the problem of signal interference due to mixing of peptide molecules, particularly agonists and antagonists, is avoided. In addition, the peptides are released from their supports in a controlled manner so that fractions are available for multiple independent tests, thus eliminating the need for iterative library analysis and resynthesis. The MUPL concept was validated with a functional screen which detects agonists to G-protein-coupled receptors and led to the discovery of new ligands. It is expected that combining MUPLs with functional assays will enhance both basic scientific research and the rates of drug discovery and development.     

A quantitative evaluation of the three dimensional reconstruction of patients' coronary arteries

BACKGROUND: Through extensive training and experience angiographers learn to mentally reconstruct the three dimensional (3D) relationships of the coronary arterial branches. Graphic computer technology can assist angiographers to more quickly visualize the coronary 3D structure from limited initial views and then help to determine additional helpful views by predicting subsequent angiograms before they are obtained. METHODS: A new computer method for facilitating 3D reconstruction and visualization of human coronary arteries was evaluated by reconstructing biplane left coronary angiograms from 30 patients. The accuracy of the reconstruction was assessed in two ways: 1) by comparing the vessel's centerlines of the actual angiograms with the centerlines of a 2D projection of the 3D model projected into the exact angle of the actual angiogram; and 2) by comparing two 3D models generated by different simultaneous pairs on angiograms. The inter- and intraobserver variability of reconstruction were evaluated by mathematically comparing the 3D model centerlines of repeated reconstructions. RESULTS: The average absolute corrected displacement of 14,662 vessel centerline points in 2D from 30 patients was 1.64 +/- 2.26 mm. The average corrected absolute displacement of 3D models generated from different biplane pairs was 7.08 +/- 3.21 mm. The intraobserver variability of absolute 3D corrected displacement was 5.22 +/- 3.39 mm. The interobserver variability was 6.6 +/- 3.1 mm. CONCLUSIONS: The centerline analyses show that the reconstruction algorithm is mathematically accurate and reproducible. The figures presented in this report put these measurement errors into clinical perspective showing that they yield an accurate representation of the clinically relevant information seen on the actual angiograms. These data show that this technique can be clinically useful by accurately displaying in three dimensions the complex relationships of the branches of the coronary arterial tree.     

Complementation of null CF mice with a human CFTR YAC transgene

We have made transgenic mice carrying a 320 kb YAC with the intact human cystic fibrosis transmembrane regulator (CFTR) gene. Mice that only express the human transgene were obtained by breeding with Cambridge null CF mice. One line has approximately two copies of the intact YAC. Mice carrying this transgene and expressing no mouse cftr appear normal and breed well, in marked contrast to the null mice, where 50% die by approximately 5 days after birth. The chloride secretory responses in these mice are as large or larger than in wild-type tissues. Expression of the transgene is highly cell type specific and matches that of the endogenous mouse gene in the crypt epithelia throughout the gut and in salivary gland tissue. However, there is no transgene expression in some tissues, such as the Brunner's glands, where it would be expected. Where there are differences between the mouse and human pattern of expression, the transgene follows the mouse pattern. We have thus defined a cloned fragment of DNA which directs physiological levels of expression in many of the specific cells where CFTR is normally expressed.     

图书馆制度与图书馆发展关系论

图书馆制度包括宏观政策工作规程和个馆微观工作规则,它们与图书馆的发展密切相关,宏观规程指导图书馆事业发展方向,加大图书馆建设发展力度,确保图书馆文化的延续与发展;微观工作规则保证了图书馆各项工作的顺利进行,加强高校图书馆法规制度建设,将会在今后的自动化、网络化、现代化建设中发挥重要作用。     

Parallel synthesis and screening of a solid phase carbohydrate library

A solid phase carbohydrate library was synthesized and screened against Bauhinia purpurea lectin. The library, which contains approximately 1300 di- and trisaccharides, was synthesized with chemical encoding on TentaGel resin so that each bead contained a single carbohydrate. Two ligands that bind more tightly to the lectin than Gal-beta-1,3-GalNAc (the known ligand) have been identified. The strategy outlined can be used to identify carbohydrate-based ligands for any receptor; however, because the derivatized beads mimic the polyvalent presentation of cell surface carbohydrates, the screen may prove especially valuable for discovering new compounds that bind to proteins participating in cell adhesion.     

量纲理论在粒子冲击钻井系统粒子分离效率研究中的应用

通过量纲分析对粒子冲击钻井分离系统实验台所得到的实验数据进行处理分析,结果发现钢质粒子损失率随着泥浆流量、黏度以及钢质粒子所占比例的增大而增大.量纲模型中表征几何特征、工作状态、泥浆流体特征以及流量等参数是主要影响因素.根据分析本文还提出了适用于多种泥浆工况下钢质粒子损失率的经验公式.     

The synthesis and screening of a combinatorial peptide library for affinity ligands for glycosylated haemoglobin

This paper reports the synthesis and screening of a combinatorial peptide library for new affinity ligands for glycosylated haemoglobin (HbA1c), which is an important indicator of diabetes control. The new ligands are suitable for large-scale synthesis and overcome the disadvantages of antibodies (unstable and expensive to produce etc.), while remaining as efficient as antibodies in binding to the analyte. The library consisted of 262,144 hexapeptides synthesised using the one-bead-one-compound technique. The hexapeptides attached onto beads were screened with glycosylated haemoglobin HbA1c. The structures of the peptides exhibiting high affinity were characterised by Edman microsequencing. Computer modelling simulation of one of the lead sequences has shown that this class of ligand has a high affinity and specificity for glycosylated haemoglobin.     

Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening

V79 (Chinese hamster lung fibroblast) cell lines expressing a functional recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UGT), i.e., UGT2B1, were established. Western blot analysis of positive colonies, using anti-rat liver UGT antibodies, revealed the presence of an immunoreactive polypeptide of the expected molecular mass of 52 kDa. The substrate specificity of the recombinant enzyme toward > 100 compounds was determined. Phenolic and alcoholic substrates included 4-methylumbelliferone, 4-hydroxybiphenyl, chloramphenicol, and testosterone, but a range of carboxylic acids of both endogenous (medium-chain saturated fatty acids, long-chain polyunsaturated fatty acids, and bile acids) and exogenous (profen nonsteroidal anti-inflammatory drugs, fibrate hypolipidemic agents, and sodium valproate) origin were also accepted, indicating that the enzyme was capable of forming both ether- and ester-type glucuronides from various structurally unrelated compounds. Determination of apparent kinetic constants for the glucuronidation by UGT2B1 of selected aglycones revealed a high maximal velocity toward the 3-position of morphine (49.3 +/- 2.2 nmol/min/mg of protein), compared with other known substrates such as 4-methylumbelliferone (2.67 +/- 0.11 nmol/min/mg of protein) or clofibric acid (0.06 +/- 0.02 nmol/min/mg of protein). To gain a better insight into the mechanisms underlying the apparently wide substrate specificity of UGT2B1, series of structurally related compounds were tested as potential substrates. The rate of glucuronidation of unbranched saturated fatty acids and omega,omega,omega-triphenylalkanoic acids increased progressively with increasing alkyl chain length and then declined, with the best substrates in these two homologous series being decanoic acid and 4,4,4-triphenylbutanoic acid, respectively. Glucuronidation of para-substituted phenols always proceeded at a higher rate than that of the corresponding para-substituted benzoic acids. This could mean that the aglycon hydroxyl group was better positioned in the enzyme active site in the case of phenols. Alternatively, if the initial interaction with the enzyme required the aglycon to be in the protonated uncharged form, then the observation could be explained by the difference in ionization between phenols and benzoic acids at the incubation pH used. The introduction of a bulky alkyl group into the para-position led to increases of up to 300-fold in the rate of glucuronidation, probably as a result of the increased aglycon lipophilicity. Finally, the enzyme showed a degree of stereo- and regiospecificity, preferring (S)-ibuprofen to the R-enantiomer (Vmax/Km, 3.06 and 1.10 microliters/min/mg of protein, respectively) and glucuronidating lithocholic acid but not hyodeoxycholic acid, which differs by only a single hydroxyl group.(ABSTRACT TRUNCATED AT 400 WORDS)     

Encoded combinatorial chemistry: synthesis and screening of a library of highly functionalized pyrrolidines

The application of a new encoding technology for drug discovery is described. A combinatorial library of mercaptoacyl pyrrolidines has been prepared on a beaded polymeric support. Each polymer bead carries one library constituent in association with an oligomeric "tag," the structure of which is a record of the specific reagents from which that library member was prepared. After the ligands were solubilized, an array of such beads was screened for angiotensin-converting enzyme inhibitory activity, and the structures of active pyrrolidines were deduced by analysis of the associated tags at sub-picomole levels. Several extremely potent enzyme inhibitors were identified, many from multiple beads. The most potent inhibitor was found to have a Ki of 160 pM, approximately 3-fold more active than captopril in the same assay. Direct comparison with iterative deconvolution shows that the encoded screening strategy is a much more efficient means for extracting information from such compound collections, producing more data on a larger number of active structures.     

Construction of a mouse blastocyst cDNA library by PCR amplification from total RNA

Prostaglandin E2 (PGE2) and beta-adrenergic agonists can suppress lipopolysaccharide-induced tumor necrosis factor-alpha (TNF) production from elicited macrophages. We assessed the responsiveness of rat peritoneal macrophages to PGE2 and the beta-adrenergic agonist isoproterenol during immunologically-mediated arthritis. We assessed macrophage sensitivity to these mediators from resident macrophages and macrophages elicited with either streptococcal cell wall or complete Freund's adjuvant. Peritoneal macrophages were obtained from female Lewis rats that were (1) injected with complete Freund's adjuvant and non-arthritic (CFA); (2) injected with streptococcal cell wall and arthritic (ART); (3) injected with streptococcal cell wall and non-reactive (NON) and (4) non-elicited resident macrophages (RES). When challenged with graded concentrations of lipopolysaccharide (0.1 to 10,000 ng/ml), macrophages obtained from each group of rats released TNF in a concentration-dependent manner, with macrophages from arthritic rats (ART) producing the greatest amount of TNF (p < 0.001). While PGE2 suppressed lipopolysaccharide (100 ng/ml) stimulated TNF production in a concentration-dependent manner in all groups, the greatest sensitivity to PGE2 was observed with macrophages obtained from rats which received streptococcal cell wall when compared to both complete Freund's adjuvant-elicited and resident macrophages (p < 0.05). The beta-adrenergic agonist isoproterenol also inhibited lipopolysaccharide-stimulated TNF production from macrophages in all groups. In addition, the specific beta 2-adrenergic antagonist, ICI 118.551, shifted isoproterenol concentration-effect curves to the right (p < 0.01). Minimal responsiveness to isoproterenol was observed with resident peritoneal macrophages. Maximum isoproterenol-induced inhibition of TNF production was observed with complete Freund's adjuvant-elicited macrophages, and significantly less in macrophages of streptococcal cell wall-injected rats. Of particular interest, macrophages obtained from streptococcal cell wall-injected rats, which became arthritic, were significantly less sensitive to isoproterenol than those which did not develop arthritis (p < 0.02). In addition, these changes in sensitivity were not reflected by changes in the sensitivity of both CFA and ART groups to dibutyryl cAMP. The present study demonstrates a shift in the balance between inhibitory mediator responses in rats inoculated with one of two different adjuvants. These investigations support the role of PGE2 and a neurotransmitter as immunomodulating compounds which may effectively maintain an inflammatory lesion such as arthritis.     

Construction and characterization of a human bacterial artificial chromosome library

A high-performance liquid chromatographic method with evaporative light-scattering detection was developed for the analysis of intact lipid classes in nervous tissue. The method had the ability to resolve plasmalogen-phosphatidyl-ethanolamine and diacyl-phosphatidylethanolamine along with other major phospholipid classes in a single run. This technique was employed for the investigation of the effects of chronic alcohol consumption on the membrane lipid class composition of human brains (alcoholics, n = 13; controls, n = 11). Measurements were performed on cholesterol, cerebrosides, sulfatides, phospholipids and sphingolipids in total lipid extracts of white matter, gray matter and cerebellar regions of human brains. No significant differences in the lipid class composition between the groups were observed.     

连铸专家质量判定系统及其应用

介绍连铸专家质量判定系统的技术特点、调教要点及实际应用进展。     

实施工序质量评价提高质量管理体系运行的有效性

总结了柳钢在质量管理体系上下工序之间开展工序质量评价的办法以及效果,提出质量管理工作的新思路.     

连铸保护渣质量评价体系探讨

连铸保护渣对连铸工艺的顺行和铸坯表面质量具有重要影响.本文初步建立了连铸保护渣质量全面评价体系,主要包括连铸保护渣成分、物理性能以及使用性能,为准确评价连铸保护渣质量优劣、减少因保护渣原因造成的连铸质量事故以及开发品种钢连铸保护渣提供了参考.     

The use of a combinatorial library method to isolate human tumor cell adhesion peptides

Tumor cell progression is dependent in part on the successful adhesive interactions of the cells with the extracellular matrix. In this study, a new approach is described to isolate linear peptide ligand candidates involved in cellular adhesion. A synthetic combinatorial peptide library based on the 'one-bead-one-peptide' concept was incubated with live human prostate cancer cells for 90 min at 37 degrees C. The peptide bead coated with a monolayer of cells was then isolated for microsequencing. The DU145 (DU-H) cells were chosen since they have been previously characterized as containing elevated levels of a laminin receptor for cell adhesion, the alpha 6 beta 1 integrin on the cell surface. The use of a function-blocking antibody (GoH3) allows for the detection of peptides which are alpha 6-specific ligand candidates. From two different libraries (linear 9-mer and 11-mer) of a total of 1,500,000 beads, 68 peptide beads containing attached cells were isolated. These positive beads were then retested to determine the ability of the GoH3 antibody to block binding of the cells to the peptide beads. The alpha 6 integrin candidate peptide beads (five in total) were recovered and two of the beads were microsequenced. These two peptides, RU-1 (LNIVS-VNGRHX) and RX-1 (DNRIRLQAKXX), resemble the previously reported active peptide sequences (GD-2 and AG-73) from native laminin. The RU-1, RX-1 and AG-73 peptides were tested for their ability to support cell attachment and to bind the cell surface of DU-H prostate carcinoma cells in suspension using fluorescence-activated cell-sorting (FACS) analysis. Both RU-1 and AG-73 peptides supported cellular attachment within 1 h. In contrast, after 1 h, EHS laminin supported both cellular attachment and spreading. The RX-1 peptide exhibited only weak binding to the DU-H prostate carcinoma cells. FACS analysis indicated that AG-73 peptide attached to tumor cell surfaces over a range of concentrations, whereas the RU-1 peptide showed a homogeneous concentration required for attachment. The described strategy for screening a random peptide library offers three advantages: (i) ligands for conformationally sensitive receptors of adhesion can be isolated using live cells; (ii) specific binding can be selected for using function-blocking antibodies; and (iii) peptides supporting adhesion independent of spreading properties can be distinguished. In principle, specific adhesive peptides without prior knowledge of the sequence could be isolated for any epithelial cell surface receptor for which a function-blocking reagent is available.     

Identification of two novel diurnal genes by screening of a rat brain cDNA library

While the hypothalamus is fundamental for sleep and circadian regulation, the molecular mechanisms involved are poorly understood. We have used a differential gene expression technique to identify hypothalamic genes which have altered expression in rat sleep periods. Complex cDNA probes from rat hypothalami removed at Zeitgeber times 4 and 15 were hybridised to rat brain cDNA library girds. From 30 differentially expressed clones, six were further analysed and two were confirmed to exhibit increased expression at Zeitgeber time 4. A Northern blot hybridization of brain, heart, kidney, lung, testis and skin mRNA showed that both clones were brain specific. Therefore, we have identified two novel brain specific diurnally expressed hypothalamic genes. Both genes may have roles in sleep or circadian regulation.