38 research outputs found
Flame retardants, surfactants and organotins in sediment and mysid shrimp of the Scheldt estuary (The Netherlands)
No full textAuthor Posting. © The Authors, 2004. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Environmental Pollution 136 (2005): 19-31, doi:10.1016/j.envpol.2004.12.008.Sediment and mysids from the Scheldt estuary, one of the largest and most polluted estuaries in Western Europe, were analyzed for a number of contaminants that have shown to possess endocrine-disrupting activity, i.e. organotins, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA), nonylphenol ethoxylates (NPE) and transformation products nonylphenol (NP) and nonylphenol ether carboxylates (NPEC). In addition, in vitro estrogenic and androgenic potencies of water and sediment extracts were determined. Total organotin concentrations ranged from 84 to 348 ng/g dw in sediment and 1110 to 1370 ng/g dw in mysid. Total PBDE (excluding BDE-209) concentrations ranged from 14 to 22 ng/g dw in sediment and from 1765 to 2962 ng/g lipid in mysid. High concentrations of BDE-209 (240-1650 ng/g dw) were detected in sediment and mysid (269-600 ng/g lipid). Total HBCD concentrations in sediment and mysid were 14-71 ng/g dw and 562-727 ng/g lipid, respectively. Total NPE concentrations in sediment were 1422 ng/g dw, 1222 ng/g dw for NP and 80 ng/g dw for NPEC and ranged from 430 to 1119 ng/g dw for total NPE and from 206 to 435 ng/g dw for NP in mysid. Significant estrogenic potency, as analyzed using the yeast estrogen assay, was detected in sediment and water samples from the Scheldt estuary, but no androgenic activity was found. This study is the first to report high levels of endocrine disruptors in estuarine mysids.Funding to Tim Verslycke was provided by a research grant of the Flemish Institute for the Promotion of Scientific and Technological Research in Industry (IWT-V, Belgium) and a postdoctoral award by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Ocean Life Institute. The chemical analysis was financially supported by the National Institute for Coastal and Marine Management (RIKZ, The Netherlands)
Parallel NMR supersequences: ten spectra in a single measurement
No full textThe principles employed in parallel NMR and MRI are applied to NMR supersequences yielding as many as ten 2D NMR spectra in one measurement. We present a number of examples where two NOAH (NMR by Ordered Acquisition using 1H-detection) supersequences are recorded in parallel, thus dramatically increasing the information content obtained in a single NMR experiment. The two parallel supersequences entangled by time-sharing schemes (IPAP-seHSQC, HSQC-COSY, and HSQC-TOCSY) incorporate also modified (sequential and/or interleaved) conventional pulse schemes (modules), including HMBC, TOCSY, COSY, CLIP-COSY, NOESY, and ROESY. Such parallel supersequences can be tailored for specific applications, for instance, the analysis and characterization of molecular structure of complex organic molecules from a single measurement. In particular, the CASPER software was used to establish the structure of a tetrasaccharide, β-LNnTOMe, with a high degree of confidence from a single measurement involving a parallel NOAH-5 supersequence
Increasing sensitivity and versatility in NMR supersequences with new HSQC-based modules
No full textThe sensitivity-enhanced HSQC, as well as HSQC-TOCSY, experiments have been modified for incorporation into NOAH (NMR by Ordered Acquisition using 1H detection) supersequences, adding diversity for 13C and 15N modules. Importantly, these heteronuclear modules have been specifically tailored to preserve the magnetisation required for subsequent acquisition of other heteronuclear or homonuclear modules in a supersequence. In addition, we present protocols for optimally combining HSQC and HSQC-TOCSY elements within the same supersequences, yielding high-quality 2D spectra suitable for structure characterisation but with greatly reduced experiment durations. We further demonstrate that these time savings can translate to increased detection sensitivity per unit time
Multiplexing experiments in NMR and multi-nuclear MRI
No full textMultiplexing NMR experiments by direct detection of multiple free induction decays (FIDs) in a single experiment offers a dramatic increase in the spectral information content and often yields significant improvement in sensitivity per unit time. Experiments with multi-FID detection have been designed with both homonuclear and multinuclear acquisition, and the advent of multiple receivers on commercial spectrometers opens up new possibilities for recording spectra from different nuclear species in parallel. Here we provide an extensive overview of such techniques, designed for applications in liquid- and solid-state NMR as well as in hyperpolarized samples. A brief overview of multinuclear MRI is also provided, to stimulate cross fertilization of ideas between the two areas of research (NMR and MRI). It is shown how such techniques enable the design of experiments that allow structure elucidation of small molecules from a single measurement. Likewise, in biomolecular NMR experiments multi-FID detection allows complete resonance assignment in proteins. Probes with multiple RF microcoils routed to multiple NMR receivers provide an alternative way of increasing the throughput of modern NMR systems, effectively reducing the cost of NMR analysis and increasing the information content at the same time. Solid-state NMR experiments have also benefited immensely from both parallel and sequential multi-FID detection in a variety of multi-dimensional pulse schemes. We are confident that multi-FID detection will become an essential component of future NMR methodologies, effectively increasing the sensitivity and information content of NMR measurements
Parallel nuclear magnetic resonance spectroscopy
No full textNuclear magnetic resonance (NMR) spectroscopy is a principal analytical technique used for the structure elucidation of molecules. This Primer covers different approaches to accelerate data acquisition and increase sensitivity of NMR measurements through parallelization, enabled by hardware design and/or pulse sequence development. Starting with hardware-based methods, we discuss coupling multiple detectors to multiple samples so each detector/sample combination provides unique information. We then cover spatio-temporal encoding, which uses magnetic field gradients and frequency-selective manipulations to parallelize multidimensional acquisition and compress it into a single shot. We also consider the parallel manipulation of different magnetization reservoirs within a sample to yield new, information-rich pulse schemes using either homonuclear or multinuclear detection. The Experimentation section describes the set-up of parallel NMR techniques. Practical examples revealing improvements in speed and sensitivity offered by the parallel methods are demonstrated in Results. Examples of use of parallelization in small-molecule analysis are discussed in Applications, with experimental constraints addressed under the Limitations and optimizations and Reproducibility and data deposition sections. The most promising future developments are considered in the Outlook, where the largest gains are expected to emerge once the discussed techniques are combined
Isolation, separation, identification, and quantification of bioactive methylated flavone regioisomers by UHPLC-MS/MS
No full textMethylated flavones, commonly found in many plants of the Brassicaceae family, have potent antioxidant and anticancer activity with diverse therapeutic potential. However, the specific regioisomers of methylated flavones can have significantly different biochemical and potentially therapeutic properties as shown by various bioassays but analytically differentiating these compounds has been technically challenging and rarely reported. In this study, we demonstrate differentiation and identification of selected bioactive methylated flavone regioisomers, namely 5,7,3′-trihydroxy-4′-methoxyflavone, and 5,7,4′-trihydroxy-3′-methoxyflavone extracted from Coronopus didymus, a member of the Brassicaceae family, using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS). Characteristic MS/MS product ions produced from neutral loss of carbon monoxide, and a methyl radical from the [M-H]– ion, exhibited differential relative abundances attributed to different structural stabilities under the same activation and collision-induced dissociation conditions. MS/MS also provided structural information which was sufficient to differentiate the methylated regioisomers and determine the position of the methyl group based on interpretation of their respective fragmentation patterns. Quantification showed 5,7,4′-trihydroxy-3′-methoxyflavone was at least 1.60 mg per 10 g plant material in C. didymus extracts. This study demonstrates a straightforward and novel approach to rapidly differentiate, identify and quantify regio-isomeric methylated flavone natural products using reversed-phase UPLC-MS/MS
Technical education and the London county council 1918-1939. A study in course innovation and development
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Our thesis is concerned with the process of course innovation and Development in technical education within the area of the London County Council During the period 1918-39. Although essential, an historical study, the Thesis is intended to be of value in a consideration of future development in Technical education, and in particular in the study of the relationship between Curriculum management and manpower planning. The first part of our thesis describes the institutional structure of the principal sectors of technical education in London and outlines the Type of courses that were available and their general progress during the Interwar years. The second part of our thesis seeks to analyse the background to course innovation and to assess why certain courses were successful and why others were comparative failures. Since the topic is potentially so vast, our thesis has been limited to an identification of major factors, rather than a detailed consideration of each one. Our analysis shows the process of course innovation and development in technical education to have been a highly complex interaction of forces in which the other aspects of the educational structure, including administrative as well as teach1ng institutions, played a vital role. Emphasis has been given to the influence of senior administrative officers within the local I education authority framework. Special mention has been made of the work of the Board of Education and of the limitations of the Board in tailing to establish definite guidelines for course development in technical education. Important factors outside the educational structure have also been considered, including the attitudes of parents and business management to formal technical training
Counterion-Mediated Enantioconvergent Synthesis of Axially Chiral Medium Rings
No full text[Image: see text] There are few enantioconvergent reactions in which racemic substrates bearing multiple stereochemical features are converted into products with high levels of diastereo- and enantiocontrol. Here, we disclose a process for the highly enantio- and diastereoselective syntheses of medium ring lactams via an intramolecular counterion-directed C-alkylation reaction. The treatment of racemic biaryl anilides that exist as a complex mixture of enantiomers and diastereoisomeric conformers by virtue of multiple axes of restricted rotation with a quinidine-derived ammonium salt under basic conditions affords medium ring lactams bearing elements of both axial and point chirality via an enolate-driven configurational relaxation process. Thermal equilibration of the syn- and anti-product diasteroisomers has demonstrated that the barriers to bowl inversion are >124 kJ mol(-1). We propose that the chiral ammonium salt differentiates between a complex and rapidly equilibrating mixture of enolate and rotational isomers, ultimately leading to highly enantioselective alkylative ring closure. This dynamic and enantioconvergent process offers an operationally simple approach to the synthesis of valuable chiral medium ring lactams for which there are few catalytic and enantioselective approaches
T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.
No full textThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedTo estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.This work was supported by European and Developing Countries Clinical Trials Partnership grant # IP.2009.33011.004; trial foods were prepared and supplied by Nutriset, Malauney, Franc
Clerodane Diterpenoids from an Edible Plant <i>Justicia insularis</i>: Discovery, Cytotoxicity, and Apoptosis Induction in Human Ovarian Cancer Cells
No full textObjectives: The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics. Justicia insularis T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored J. insularis and investigate their underlying mechanism of action. Methods: The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identified active compounds. Key finding: The two cytotoxic compounds were identified as clerodane diterpenoids: 16(α/β)-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide (1) and 16-oxo-cleroda-3,13(14)E-dien-15-oic acid (2) from the Acanthaceous plant for the first time. Compound 1 was a very abundant compound (0.7% per dry weight of plant material) and was shown to be more potent than compound 2 with IC50 values in the micromolar range against OVCAR-4 and OVCAR-8 cancer cells. Compounds 1 and 2 were less cytotoxic to HOE cell line. Both compounds induced apoptosis by increasing caspase 3/7 activities in a concentration dependent manner. Compound 1 further increased caspase 8 and 9 activities and apoptosis cell populations. Compounds 1 and 2 are both drug like, and compound 1 may target various proteins including a kinase. Conclusions: Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer
