免疫细胞素Hu14.18-IL-2对黑色素瘤病人的免疫激活作用

目的评估免疫细胞素Hu14.18-IL-2对黑色素瘤病人体内免疫作用。方法33位黑色素瘤病人用一种人源化抗神经节苷脂GD-2的单抗与IL-2融合的免疫细胞素进行治疗,按每天0.8、1.6、3.2、4.8、6.0、7.5 mg/m2静脉滴注,连续3 d为一疗程,病情稳定或缓解后,在第5周接受第2疗程治疗。观察病人外周血单核淋巴细胞抗体依赖的细胞毒性、自然杀伤细胞活性、IL-2的体外增殖以及IL-2可溶性受体的变化。结果Hu14.18-IL-2能诱导病人淋巴细胞的吞噬作用,增强外周血中自然杀伤细胞的杀伤能力和数目,使血清中IL-2受体复合体的可溶性受体α链水平上升。结论免疫细胞素Hu14.18-IL-2对黑色素瘤病人具有免疫激活作用。     

Engineering linear F(ab')2 fragments for efficient production in Escherichia coli and enhanced antiproliferative activity

We developed a novel bivalent antibody fragment, the linear(L-) F(ab')₂, comprising tandem repeats of a heavy chain fragmentV_H–C_H1–V_H–C_H1 cosecreted with a light chain.Functional humanized L-F(ab')₂ directed against p185^HER2 wassecreted from Escherichia coli at high titer (100 mg/l) andpurified to homogeneity. The L-F(ab')₂ binds two equivalentsof antigen with an apparent affinity (K_d = 0.46 nM) that iswithin 3-fold of the corresponding thioether-linked F(ab')₂fragment The N-terminal site binds antigen with an affinity(K_d = 1.2 nM) that is 4-fold greater than that for the C-terminalsite, as shown by the comparison of L-F(ab')₂ variants containinga single functional binding site. L-F(ab')₂ has greater antiproliferativeactivity than the thioether-linked F(ab')₂ against the p185^HER2-overexpressingtumor cell line BT474. Linear and thioether-linked F(ab')₂ havevery similar pharmacokinetic properties in normal mice, andtheir serum permanence times are respectively 7- and 8-foldlonger than the corresponding Fab fragment L-F(ab')₂ offersa facile route to bivalent antibody fragments that are potentiallysuitable for clinical applications, and that may have improvedbiological activity compared with thioether-linked F(ab')₂ fragments.     

Sintering ZrO2/TiC Composites with TiH2: The Role of Transient Liquid Phase and of Substoichiometry

Sintering tetragonal ZrO₂ with 35 vol% TiC results in a microstructure where all grain facets are free of amorphous interfaces independent of sintering aids as TiH₂ or MgO/ Y₂O₃; grain sizes are below 1 μm. With substoichiometric TiC_1-x, a relative density of 95% and closed porosity are obtained at a lower sintering temperature than with stoichiometric TiC, but subsequent cladless hot isostatic pressing (HIP) is required to achieve 99% density. High densities of 98% accompanied by good mechanical properties become possible by pressureless sintering with the use of TiH₂. MgO/Y₂O₃ doping also promotes densification, but results in less transformable zirconia and increases the number and size of amorphous triple junctions. The consequences are a lower fracture toughness and strength.     

Use of artificial intelligence in analytical systems for the clinical laboratory

The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI), both as expert systems and as neural networks.This paper considers the role of software in system operation, control and automation, and attempts to define intelligence. AI is characterized by its ability to deal with incomplete and imprecise information and to accumulate knowledge. Expert systems, building on standard computing techniques, depend heavily on the domain experts and knowledge engineers that have programmed them to represent the real world. Neural networks are intended to emulate the pattern-recognition and parallel processing capabilities of the human brain and are taught rather than programmed. The future may lie in a combination of the recognition ability of the neural network and the rationalization capability of the expert system.In the second part of the paper, examples are given of applications of AI in stand-alone systems for knowledge engineering and medical diagnosis and in embedded systems for failure detection, image analysis, user interfacing, natural language processing, robotics and machine learning, as related to clinical laboratories.It is concluded that AI constitutes a collective form of intellectual propery, and that there is a need for better documentation, evaluation and regulation of the systems already being used in clinical laboratories.     

Polyacrylonitrile-reinforced poly(vinyl alcohol) membranes: Mechanical and dialysis performance

Membranes used for hemodialysis should have good mechanical strength to withstand the maximum transmembrane pressure. Although crosslinked poly(vinyl alcohol) membrane has superior permeability to solutes, its wet breaking strength is low. Mechanical strength, dry and wet, of membranes made from crosslinked blendmers of poly(vinyl alcohol) and polyacrylonitrile was investigated. The possibilities of these membranes for the application as dialysis membranes were evaluated by estimating its solute permeabilities. The optimum membrane selected shows permeability and mechanical properties comparable with the commercial regenerated cellulose membrane. Polyelectrolyte grafting made the membrane more blood-compatible. © 1995 John Wiley & Sons, Inc.     

A Multi-Disciplinary Contribution to the Provenance Determination of Ancient Greek and Roman Marble Artifacts

The problem of determining the provenance of the white marble used for antique artifacts has been tackled in different ways. During the past decade it became clear that a multimethod approach is required to solve the problem. In addition, reliable reference material, i.e., samples collected at the ancient quarry sites in an archaeologically and geologically justified manner, turned out to be a prerequisite for reliable provenance determination. A multimethod approach based on petrography, stable isotope analysis of O and C, and trace element analysis yields complementary information. These methods were applied to the same set of 225 quarry samples. When processed with powerful statistical methods, the data thus obtained allowed all major types of marble used in antiquity to be distinguished. Thus, most problems concerning the provenance of artifacts can be solved. This approach was successfully applied to the provenance determination of about 75 artifacts from different museums in Europe and the USA.     

Effect of seawater constituents on the performance of thermal spray aluminum in marine environments

Thermally sprayed coatings are often used to mitigate corrosion of offshore structures. They act as a physical barrier to the aggressive marine environment and as a sacrificial distributed anode for low carbon steel. In such environments, the severity of material degradation depends on many factors. The effect of temperature, exposure time or the presence of micro‐organisms are the focus of many studies, for example, however, the effect of the different ions present in seawater remains largely unexplored. The chemical composition of the water changes considerably depending on the location; industrial, glacial, estuarine, and so forth. In addition, when thermal spray aluminum (TSA) protects steel in seawater, calcareous matter precipitates as a result of the cathodic polarization and subsequent localized increase in pH. Therefore, understanding how ions such as magnesium (II), calcium (II), or carbonates alter the coating properties in the marine environment is important. This paper reports the experimental work carried out with TSA‐coated steel samples with defects to simulate mechanical damage or erosion of the coating. The combination of electrochemical tests and surface characterization provided evidence of the efficiency of the calcareous bilayer that forms on top of steel reducing the TSA degradation.     

Effects of bile salts on rat hepatic acyl CoA:Cholesterol acyltransferase

Acyl CoA:cholesterol acyltransferase (EC2.3.1.26, ACAT), responsible for intracellular esterification of cholesterol, may play an important role in cholesterol trafficking within the cell, and thus, in maintenance of cellular cholesterol homeostasis. Bile acids are potential regulators of cholesterol trafficking in the liver. Therefore, the effect of bile salts on hepatic ACAT activity was studied in the perfused rat liver. ACAT activity was increased after liver perfusion with either taurocholate or taurochenodeoxycholate. However, addition of these bile salts at physiological concentrationsin vitro had little effect on microsomal ACAT activity. The increase in hepatic ACAT activity due to perfusion with bile salts was accompanied by reduced accumulation of very low density lipoprotein cholesterol in the perfusate, but there was no effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. Hepatic ACAT activity was decreased after bile diversion for four hours in the intact animal. This treatment had no statistically significant effect on 3-hydroxy-3-methylglutaryl-CoA reductase activity. These data suggest that bile salts induce changes in hepatic compartmentation and traffic of cholesterol within the hepatocyte accompanied by response of ACAT activity to maintain cellular cholesterol homeostasis.     

The role ofAzolla in curbing ammonia volatilization from flooded rice systems

By the year 2020, an additional 300 million tons of rice are needed annually to meet the demands of a growing population. If our natural resource base is to be preserved, intensification strategies should rely on integrated nutrient management, making full use of biological nitrogen fixation. TheAzolla-Anabaena complex is amongst the most effective systems of fixing nitrogen. In this paper we present evidence from greenhouse studies on the potential ofAzolla to curb the volatilization of NH₃ following the application of urea to a mixedAzolla-rice culture, providing a new incentive for developing ways of integratingAzolla in intensive rice cultivation systems.The results of a series of short term greenhouse experiments show that a full cover ofAzolla can significantly reduce losses of applied urea-N from 45 and 50% to 20 and 13% for the 30 and 60 kg N ha^–1 treatments, respectively. About one-quarter of the applied N was tied up in theAzolla biomass. The applied N inhibitedAzolla growth as well as the amount of N fixed. Inoculation with smaller quantities ofAzolla allowing for more vigorousAzolla multiplication was equally effective in reducing NH₃ volatilization and doubled the amount of¹⁵N tied-up byAzolla. The reduction in NH₃ volatilization is largely related to the depression byAzolla of the floodwater pH, which in its absence may reach values between 9 and 10 as a result of algal activity.Early rice growth responded positively to urea as well as the large quantities of appliedAzolla and increased the yield potential of the crop. Smaller quantities ofAzolla alone were not effective in this regard. The conservation of fertilizer N byAzolla, particularly when it fully covered the water, was reflected in a synergistic effect on rice dry matter production, amounting to 9% at the 30 kg N rate and 16% at the 60 kg N rate. In all likelihood this interaction is attributable to the higher efficiency of the applied N. The benefits ofAzolla in conserving basal urea-N even in small quantities (200-500 kg fresh material ha^–1), outweighed competition for the applied N and may be as important as its BNF. The most promising integratedAzolla/rice management systems emerging from our studies should be given further attention under field conditions.