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121.
Erika Lattová Eilean J. McKenzie Marco L. H. Gruwel Vic Spicer Radoslav Goldman Hélène Perreault 《Rapid communications in mass spectrometry : RCM》2009,23(18):2983-2995
Woodchucks have been a preferred lab animal model of chronic hepatitis B viral infection. The model recapitulates the disease progression of HBV infection to hepatocellular carcinoma (HCC) and has documented similarities in protein glycosylation with human HCC. This study examined N‐glycans in serum of animals with(out) HCC. Oligosaccharides were released enzymatically using PNGaseF from total serum or from serum partially fractionated by extraction. Two different extraction procedures – reversed‐phase high‐performance liquid chromatography (RP‐HPLC) and solid‐phase extraction (SPE) on a cation‐exchange/reversed‐phase STRATA‐XC cartridge – were used with the purpose of confirming glycosylation profiles. Oligosaccharides were analyzed by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) after derivatization with phenylhydrazine and/or permethylation. Characteristic fragment ions produced under MS/MS conditions allowed discrimination between isomeric structures of oligosaccharides, including those sialylated with two types of acidic residues. The complementary methods allowed structural characterization of oligosaccharides from various N‐glycan classes. Furthermore, to validate results, glycosylation profiles of woodchuck sera were compared to glycans obtained from mouse serum on the same conditions. In summary, we have identified 40 N‐glycan structures in the serum of woodchucks and some types of oligosaccharide structures appeared to increase in HCC samples following protease digest. The study provides improved tools for the characterization of N‐glycans from total serum in the progression of liver disease. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
122.
123.
W. E. Spicer 《固体与材料科学评论》1976,6(3):317-336
In the decades after World War 11, there was an explosion of fundamental research in solids and practical applications thereof. Although surfaces were not ignored in this work, until recently they were not strongly emphasized. In the last few years there has been a growing emphasis on the study of surfaces and related interfaces. There are several reasons for hs. First, as knowledge regarding the bulk properties of solids became increasingly complete, it became more and more evident how little was known about the surfaces. Thus, the study of surfaces is an exciting new frontier of scientific knowledge. Secondly, the development of devices and processes that depend on surfaces has been increasingly hindered by the lack of knowledge about surfaces, interfaces, and interactions that take place on surfaces. As a result, new techniques for experimental studies of surfaces have recently been developed.1,2 These show great promise for allowing examination of surfaces and interfaces on a microscopic and even atomic level, and for the gathering of detded information impossible to obtain in the past. Finally, theoretical methods3 are being rapidly developed, which provide increasingly detailed insight into surfaces and interactions on surfaces. 相似文献
124.
Differential cross sections for the elastic and inelastic scattering of protons by 17O have been measured at 8.62, 9.45 and 10.5 MeV. Excitation functions at 110° and 140° were measured from 8.5 to 10.5 MeV. The elastic scattering angular distributions were used to find optical model parameters for the scattering. The angular distributions of inelastically scattered protons were analysed using the effective interaction method of Satchler, and also with the microscopic theory of Geramb and Amos. 相似文献
125.
Tsuboi K Bachovchin DA Speers AE Spicer TP Fernandez-Vega V Hodder P Rosen H Cravatt BF 《Journal of the American Chemical Society》2011,133(41):16605-16616
Glutathione S-transferases (GSTs) are a superfamily of enzymes that conjugate glutathione to a wide variety of both exogenous and endogenous compounds for biotransformation and/or removal. Glutathione S-tranferase omega 1 (GSTO1) is highly expressed in human cancer cells, where it has been suggested to play a role in detoxification of chemotherapeutic agents. Selective inhibitors of GSTO1 are, however, required to test the role that this enzyme plays in cancer and other (patho)physiological processes. With this goal in mind, we performed a fluorescence polarization activity-based protein profiling (fluopol-ABPP) high-throughput screen (HTS) with GSTO1 and the Molecular Libraries Small Molecule Repository (MLSMR) 300K+ compound library. This screen identified a class of selective and irreversible α-chloroacetamide inhibitors of GSTO1, which were optimized to generate an agent KT53 that inactivates GSTO1 with excellent in vitro (IC(50) = 21 nM) and in situ (IC(50) = 35 nM) potency. Cancer cells treated with KT53 show heightened sensitivity to the cytotoxic effects of cisplatin, supporting a role for GSTO1 in chemotherapy resistance. 相似文献
126.
以CuCl2·3H2O,Cu(CH3COO)2·H2O和CuSO4·5H2O作为铜源,并向反应体系中引入少量NaCl或NaNO3,通过乙二醇溶剂中的溶剂热反应,合成了形貌各异的CuS微晶.结合XRD和SEM表征,初步探讨了阴离子Cl-、CH3COO-、SO4^2-和阳离子Na’对CuS微晶生长过程的影响.结果表明,Na+对CuS微晶的生长过程没有显著影响,而Cl、CH3COO-、SO4^2-由于在{1012}晶面上选择性吸附能力的差异,显著影响CuS微晶的形貌.本研究为进一步有效调控CuS微晶的形貌及性能奠定了基础. 相似文献
127.
Adibekian A Martin BR Chang JW Hsu KL Tsuboi K Bachovchin DA Speers AE Brown SJ Spicer T Fernandez-Vega V Ferguson J Hodder PS Rosen H Cravatt BF 《Journal of the American Chemical Society》2012,134(25):10345-10348
The development of small-molecule inhibitors for perturbing enzyme function requires assays to confirm that the inhibitors interact with their enzymatic targets in vivo. Determining target engagement in vivo can be particularly challenging for poorly characterized enzymes that lack known biomarkers (e.g., endogenous substrates and products) to report on their inhibition. Here, we describe a competitive activity-based protein profiling (ABPP) method for measuring the binding of reversible inhibitors to enzymes in animal models. Key to the success of this approach is the use of activity-based probes that show tempered rates of reactivity with enzymes, such that competition for target engagement with reversible inhibitors can be measured in vivo. We apply the competitive ABPP strategy to evaluate a newly described class of piperazine amide reversible inhibitors for the serine hydrolases LYPLA1 and LYPLA2, two enzymes for which selective, in vivo active inhibitors are lacking. Competitive ABPP identified individual piperazine amides that selectively inhibit LYPLA1 or LYPLA2 in mice. In summary, competitive ABPP adapted to operate with moderately reactive probes can assess the target engagement of reversible inhibitors in animal models to facilitate the discovery of small-molecule probes for characterizing enzyme function in vivo. 相似文献
128.
Ramnial T Abernethy CD Spicer MD McKenzie ID Gay ID Clyburne JA 《Inorganic chemistry》2003,42(5):1391-1393
The structure of 1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidene-silver(I) chloride, 1, has been determined to be a monomer with weak head-to-tail H...Cl interactions in the solid state. A multinuclear NMR study using a (13)C(carbene) labeled derivative, 1((13)C), exhibits (13)C-(107,109)Ag coupling in solution. Further, the solid state CP/MAS NMR parameters, including the principal components of the chemical shift tensors for both the (13)C and (109)Ag centers, have been determined. With the aid of DFT calculations, the orientation of the chemical shift tensors have been assigned. 相似文献
129.
M. A. Chaudhri G. Burns E. Reen J. L. Rouse B. M. Spicer 《Journal of Radioanalytical and Nuclear Chemistry》1977,37(1):243-253
A simple method for calculating the sensitivity for detecting a nuclide distributed uniformly in any given matrix through
charged particle activation is described. This method takes into account the actual values of the reaction cross section at
different energies as the beam traverses through a thick target and the corresponding stopping power values. The detection
sensitivity for fluorine in a number of matrices through the19F(p, αγ)16O reaction have been calculated as a function of the energy from threshold to 4.16 MeV using this method and the sensitivity
curves plotted. The sensitivity values (dps/ppm/μA) for a thick or thin target and even for a layer of known thickness at
a particular depth within a sample can be directly read from these curves for known bombarding conditions. The comparator
methods for charged particle activation analysis of RICCI1 and of CHAUDHRI,2 especially when the matrices of the sample and standard are different, have been compared in the case of F determination
through the19F(p, αγ)16O reaction. It has been found that the errors are reduced by almost a factor of two when the latter method is used compared
to the former one. The fluorine concentration in animal bones and teeth, apatite crystal, and rocks have been determined through
the19F(p, αγ)16O reaction using the Melbourne University Pelletron. 相似文献
130.