Hydrophilic interaction liquid chromatography-tandem mass spectrometry determination of estrogen conjugates in human urine

We report a hydrophilic interaction liquid chromatography (HILIC) separation with tandem mass spectrometry (MS) detection method for analysis of seven urinary estrogen conjugates. HILIC separation employing a mobile phase with high organic solvent content resulted in enhanced electrospray ionization efficiency and MS sensitivity compared with reversed-phase (RP) LC-MS methods. Solid-phase extraction (SPE) was used to further improve the limit of detection and to eliminate interferences for the analysis of urine samples. No hydrolysis or derivatization was required in the sample pretreatment. This SPE/HILIC-MS/MS method provided limits of quantification (LOQs at S/N = 10) for the seven conjugates ranging from 2 to 1000 pg/mL with only 1 mL of urine sample, representing an improvement of 1 order of magnitude over the RPLC tandem MS methods previously reported. This method provided a linear dynamic range of 3 orders of magnitude, recovery of 92-109%, intraday accuracy of 84-109%, intraday precision of 1-14%, interday accuracy of 80-111%, and interday precision of 1-22%. We have successfully applied this technique to determine the seven estrogen conjugates in urine samples of a pregnant woman and found unique concentration changes of six estrogen conjugates at different stages of pregnancy while the concentration of estriol-3-glucuronide (E3-3G) remained constant. We further studied the profiles of individual estrogen conjugates in breast cancer patients before and after treatment and found patient-dependent effects of aromatase inhibitor treatment on estrogen phase-II metabolism, which have not been reported previously. This study demonstrates the potential clinical application of the HILIC-MS/MS technique for sensitive monitoring of the changes of urinary estrogen conjugates in a clinical setting.     

Analysis of steroid conjugates in sewage influent and effluent by liquid chromatography-tandem mass spectrometry

Environmental endocrine disruptors such as estrone (E1) and beta-estradiol (E2) are excreted in human urine primarily as water-soluble glucuronides and sulfates that can dissociate in wastewater treatment systems to the more active free estrogens. Measurement of the distribution and fate of the steroid conjugates and the corresponding free estrogens in treatment plants and receiving waters is critical for understanding the reproductive and developmental effects of these substances on aquatic organisms. A sensitive method to measure steroid estrogen conjugates in matrix-rich sewage influents and effluents (method detection limits ranged from 0.04 to 0.28 ng/L) has been developed using HPLC tandem mass spectrometry with electrospray ionization. The method employs extensive sample purification by selective extraction from an Oasis HLB solid-phase cartridge followed by separation by anion exchange chromatography. This purification scheme, combined with a stable isotope dilution approach, was used to overcome problems of matrix suppression of ionization and permitted selective and sensitive detection of six target conjugates of E1 and E2. Accurate quantitation was highly dependent on the method of sample preservation. Acidification of each sample (pH 2.0) was effective in preventing enzymatic or chemical decomposition of steroid conjugates in all sample types, whereas glucuronide conjugates were hydrolyzed in the presence of mercury and formalin preservatives. Measured concentrations of steroid sulfates in the influent to a sewage treatment plant were approximately 100 times greater than that of the respective steroid glucuronides, suggesting that the preponderance of glucuronides had dissociated prior to reaching the treatment plant. A small percentage of the steroid sulfates persisted through biological treatment of sewage and was measured in the effluent. Steroid conjugates that survive decomposition or bypass biological treatment of municipal wastewater are released into surface waters and may serve as a source of free steroids.     

Structural investigation of PEG-fibrinogen conjugates

Controllable bio-synthetic polymeric hydrogels made from fibrinogen-poly(ethylene glycol) adducts have been successfully employed in tissue engineering. The structural consequences of PEG conjugation to fibrinogen (i.e., PEGylation) in such a hydrogel network are not fully understood. The current investigation details the structural alterations caused to the reduced fibrinogen polypeptides by the covalent attachment of linear or branched PEG chains. The structure of PEGylated fibrinogen polypeptides were comprehensively characterized using small angle X-ray scattering, light scattering, and cryo-transmission electron microscopy. These characterizations concur that the bio-synthetic hybrids self-assemble into elongated objects, having a protein core of about 50 Å in diameter decorated with multiple PEG chains. Conjugates with branched PEG chains were shorter, and have lower average molecular weight compared to conjugates with linear chains. The diameter of the protein core of both samples was similar, suggesting a tail-to-head aggregation of the PEGylated fibrinogen polypeptide. A more complete understanding of this unique structural arrangement can provide further insight into the full extent of biofunctional accessibility in a biomaterial that combines the advantages of synthetic polymers with bioactive proteins.     

BIOSEP膜-生物反应器处理城市污水

法国威力雅水务(Veolia Water)开发的膜生物反应工艺--BIOSEP技术,其城市污水处理应用工程之一的德吕镇(Thelus)污水站已运行4年.在经过长期运行后,对其进行处理效果进行了一次为期3周的评估.在进水sS最高达868 mg/L、CoD(化学需氧量)在932～1 890 mg/L的情况下,污水站出水SS(悬浮固体)小于2 mg/L,COD小于30 mg/L,去除率在98%以上.但其存在出水中硝酸盐氮过高的问题.而对于膜组件的运行中膜堵塞的问题,4年实际运行过程中,在化学浸泡清洗对膜通量的提高效率有限的情况下,优化膜滤运行方式对预防膜堵塞、稳定膜通量有着良好的效果.     

Vermitechnology for sewage sludge recycling

The present paper is aimed at safe reuse and recycling of sewage sludge (SS) and production of good quality compost using vermicomposting. Three different earthworm species Eiseniafetida (E. fetida), Eudrilus eugeniae (E. eugeniae), Perionyx excavatus (P. excavatus) in individual and combinations were utilized to compare the suitability of worm species for composting of sewage sludge as well as the quality of the end product. The sewage sludge without blending can be directly converted into good quality fertilizer (vermicompost). Vermicomposting resulted in reduction in C/N ratio 25.6 to 6-9, TOC (25%) but increase in electrical conductivity (EC) (47-51%), total nitrogen (TN) (2.4-2.8 times), potassium (45-71%), calcium (49-62%), sodium (62-82%) and total phosphorous (TP) (1.5-1.8 times), which indicated that sewage sludge can be recycled as a good quality fertilizer. The present study also inferred that the application of sewage sludge in the agricultural fields after vermicomposting would not have any adverse effect as the heavy metals (Cu, Mn, Pb and Zn) are now within the permissible limits.     

Measuring originality in science

Scientometrics - Originality has self-evident importance for science, but objectively measuring originality poses a formidable challenge. We conceptualise originality as the degree to which a...     

Glass-ceramic from sewage sludge ash

Glass-ceramic was produced by adding limestone to sewage sludge incinerated ash. Black glass was produced by melting a blended ash batch at 1450°C. For nucleation, this glass was reheated at 800°C for 1 h, and reheated at 1100°C for 2 h to form glass-ceramic. The main components of sewage sludge incinerated ash are SiO2 and Al2O3. Because small amounts of Fe2O3, sulfur and carbon are included, the addition of limestone alone can generate the crystal nucleant, FeS, to form anorthite (CaO·Al2O3·2SiO2) crystal. The glass-ceramic showed superior characteristics of high strength and acid resistance for use in construction materials. This revised version was published online in November 2006 with corrections to the Cover Date.     

Light-activated nanotube-porphyrin conjugates as effective antiviral agents

Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex?vivo reusable antiviral agents.     

Comparative cytotoxicity of gold-doxorubicin and InP-doxorubicin conjugates

Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.     

Ultrasensitive DNA detection using oligonucleotide-silver nanoparticle conjugates

Oligonucleotide-gold nanoparticle (OGN) conjugates are powerful tools for the detection of target DNA sequences due to the unique properties conferred upon the oligonucleotide by the nanoparticle. Practically all the research and applications of these conjugates have used gold nanoparticles to the exclusion of other noble metal nanoparticles. Here we report the synthesis of oligonucleotide-silver nanoparticle (OSN) conjugates and demonstrate their use in a sandwich assay format. The OSN conjugates have practically identical properties to their gold analogues and due to their vastly greater extinction coefficient both visual and absorption analyses can occur at much lower concentrations. This is the first report of OSN conjugates being successfully used for target DNA detection and offers improved sensitivity which is of interest to a range of scientists.     

三坐标测量机面向测量任务的测量精度分析

本文主要分析测量条件对三坐标测量机测量精度的影响,并对可能出现的影响因素进行简述,最后,通过具体实例进一步验证测量条件对测量结果的影响,得出三坐标测量机出厂给出的测量精度并不能代表使用中的实际测量精度的结论。     

钢卷尺示值误差测量值的不确定度评定

本文根据《JJG4-2015钢卷尺检定规程》对钢卷尺示值误差测量值的不确定度的评定方法进行了分析,并对其相关测量模型、灵敏系数、输入量的标准不确定度、合成不确定度和扩展不确定度进行了阐述。     

齿轮测量中心标准中齿廓倾斜偏差测量不确定度评定

依据JJF 1561-2016《齿轮测量中心校准规范》的规定,对齿轮测量中心标准中齿廓倾斜偏差的测量值的不确定度进行评定。     

Ex-situ bioremediation of polycyclic aromatic hydrocarbons in sewage sludge

Polycyclic aromatic hydrocarbons (PAH) are regarded as environmental pollutants. A promising approach to reduce PAH pollution is based on the implementation of the natural potential of some microorganisms to utilize hydrocarbons. In this study Proteiniphilum acetatigenes was used for bioaugmentation of sewage sludge to improve the PAH removal. Bioaugmentation experiments were performed in parallel semi-continuously fed reactors started up with digested primary and secondary sludge. Three bioaugmentation approaches were investigated: A1, addition of bacteria once during starting up; A2, addition of bacteria at the beginning and then every 2nd day and A3, addition of encapsulated bacteria once during starting up. Removal of PAH was found to be both biotic and abiotic. All three approaches had a positive effect of the biological removal of PAH. Highest biological removal of individual PAH (up to 80%) was observed using continuous addition (approach A2) of the bacteria to the reactors. In general, the effect of bioaugmentation was higher in the reactors fed with primary sludge compared to the reactors fed with mixed sludge. Bioaugmentation resulted in biological removal of low molecular weight PAH in the reactors fed with primary sludge using all three approaches while clear biological removal of the medium- and high molecular weight PAH only was observed if the bacteria were added continuously (approach A2).     

双光束法测速度时测量角产生的影响

本文讲述了利用双光束法进行无接触流速的测量。并着重讨论和分析了不同测量角所带来的不同影响,以及最佳测量角的选定。     

Measuring reuse in hazard analysis

Hazard analysis for safety-critical systems require sufficient coverage and rigour to instill confidence that the majority of hazardous consequences have been identified. These requirements are commonly met through the use of exhaustive hazard analysis techniques. However, such techniques are time consuming and error-prone. As an attempt at exhaustive coverage, hazard analysts typically employ reuse mechanisms such as copy-and-paste. Unfortunately, if reuse is applied inappropriately there is a risk that the reuse is at the cost of rigour in the analysis. This potential risk to the validity of the analysis is dependent on the nature and amount of reuse applied.This paper investigates hazard analysis reuse over two case studies. Initially reuse in an existing safety argument is described. Argument structures within the hazard analysis are identified and the amount of verbatim reuse examined. A second study is concerned with how reuse changes as a result of tool support. In contrast to the first case, the defined arguments are more diverse—reuse has occurred but is less verbatim in nature. Although tool support has aided the customisation of the reused arguments, many are only trivially customised. An edit distance algorithm is utilised to identify and enumerate verbatim and trivial reuse in the arguments.     

表面粗糙度仪的测量系统分析

本文以JB-1C型表面粗糙度测试仪组成的测景系统为研究对象,制定了表面粗糙度仪测量系统分析计划.采用均值-极差法对测量系统的重复性与再现性的分析步骤、计算过程、计算结果做了详尽的剖析和讨论.认为该测量系统的偏倚、线性和稳定性能满足要求,其重复性与再现性指标10%≤%R&R=17.9%<30%.测量系统可以接受.