bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly sensitive localization analysis of gangliosides and sulfatides including structural isomers in mouse cerebellum sections by combination of laser microdissection and hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry with theoretically expanded multiple reaction monitoring
Authors: Ikeda Kazutaka , Taguchi Ryo 
Published: September 2010

AbstractLiquid chromatography/electrospray ionization mass spectrometry (LC/ESI‐MS) is suitable for analysis of glycosphingolipids such as fragile gangliosides avoiding the use of the sialic acid elimination. However, it was not possible to distinguish the structural isomers such as GD1a and GD1b with reversed‐phase LC/ESI‐MS by hydrophobic interaction. Here we report an effective method for targeted analysis of theoretically expanded ganglioside molecular species including structural isomers by hydrophilic interaction liquid chromatography (HILIC)/ESI‐MS with multiple reaction monitoring (MRM). As a result of MRM analysis of glycosphingolipid mixtures from porcine brain, each of the lipid classes was detected within 25 min in the following order: sulfatides > GM3 > GM2 > GM1 > GD3 > GD1a > GD2 > GD1b > GT1a > GT1b > GQ1b. For the advanced application, localization analysis of postnatal day 15 (P15) mouse cerebellum layered structures was carried out by combination of MRM and laser microdissection (LMD). As a result, GM3, GD1a, GT1b and GQ1b were abundantly detected in the molecular and granular layers, whereas GM1 was widely presented in each layered structure. These gangliosides were mainly composed of d18:1‐18:0 and d18:1‐20:0, but GM3 was d18:1‐16:0 and d18:1‐20:0. Meanwhile, sulfatide molecular species were mostly localized in the myelinated fibers and scarcely found in the molecular layer. These results suggested that our method is suitable to detect a variety of ganglioside classes and sulfatides with high sensitivity at the molecular species level and effective for localization analysis of these glycosphingolipids from mouse brain sections. Copyright © 2010 John Wiley & Sons, Ltd.
Elucidation of the decomposition pathways of protonated and deprotonated estrone ions: application to the identification of photolysis products
Authors: Bourcier Sophie , Poisson Clémentine , Souissi Yasmine , Kinani Said , Bouchonnet Stéphane , Sablier Michel 
Published: September 2010

AbstractWith the future aim of elucidating the unknown structures of estrogen degradation products, we characterized the dissociation pathways of protonated estrone (E1) under collisional activation in liquid chromatography/tandem mass spectrometry (LC/MS/MS) experiments employing a quadrupole time‐of‐flight mass spectrometer. Positive ion and negative ion modes give information on the protonated and deprotonated molecules and their product ions. The mass spectra of estrone methyl ether (CH3‐E1) and estrone‐d4 (E1‐d4) were compared with that of E1 in order (i) to elucidate the dissociation mechanisms of protonated and deprotonated molecules and (ii) to propose likely structures for each product ions. The positive ion acquisition mode yielded more fragmentation. The mass spectra of E1 were compared with those of estradiol (E2), estriol (E3) and 17‐ethynylestradiol (EE2). This comparison allowed the identification of marker ions for each ring of the estrogenic structure. Accurate mass measurements have been carried out for all the identified ions. The resulting ions revealed to be useful for the characterization of structural modifications induced by photolysis on each ring of the estrone molecule. These results are very promising for the determination of new metabolites in the environment. Copyright © 2010 John Wiley & Sons, Ltd.
Food contaminant analysis at ultra‐high mass resolution: application of hybrid linear ion trap – orbitrap mass spectrometry for the determination of the polyether toxins, azaspiracids, in shellfish
Authors: Škrabáková Zuzana , O'Halloran John , van Pelt Frank N.A.M. , James Kevin J. 
Published: September 2010

AbstractThe biotoxins, azaspiracids (AZAs), from marine phytoplankton accumulate in shellfish and affect human health by causing severe gastrointestinal disturbance, diarrhea, nausea and vomiting. Specific and sensitive methods have been developed and validated for the determination of the most commonly occurring azaspiracid analogs. An LTQ Orbitrap mass spectrometer is a hybrid instrument that combines linear ion trap (LIT) mass spectrometry (MS) with high‐resolution Fourier transform (FT) MS and this was exploited to perform simultaneous ultra‐high‐resolution full‐scan MS analysis and collision‐induced dissociation (CID) tandem mass spectrometry (MS/MS). Using the highest mass resolution setting (100 000 FWHM) in full‐scan mode, the methodology was validated for the determination of six AZAs in mussel (Mytilus galloprovincialis) tissue extracts. Ultra‐high mass resolution, together with a narrow mass tolerance window of ±2 mDa, dramatically improved detection sensitivity. In addition to employing chromatographic resolution to distinguish between the isomeric azaspiracid analogs, AZA1/AZA6 and AZA4/AZA5, higher energy collisionally induced dissociation (HCD) fragmentation on selected precursor ions were performed in parallel with full‐scan FTMS. Using HCD MS/MS, most precursor and product ion masses were determined within 1 ppm of the theoretical m/z values throughout the mass spectral range and this enhanced the reliability of analyte identity.For the analysis of mussels (M. galloprovincialis), the method limit of quantitation (LOQ) was 0.010 µg/g using full‐scan FTMS and this was comparable with the LOQ (0.007 µg/g) using CID MS/MS. The repeatability data were; intra‐day RSD% (1.8–4.4%; n = 6) and inter‐day RSD% (4.7–8.6%; n = 3). Application of these methods to the analysis of mussels (M. edulis) that were naturally contaminated with azaspiracids, using high‐resolution full‐scan Orbitrap MS and low‐resolution CID MS/MS, produced equivalent quantitative data. Copyright © 2010 John Wiley & Sons, Ltd.
Geographic origin of southern Brazilian wines by carbon and oxygen isotope analyses
Authors: Adami Laurien , Dutra Sandra Valduga , Marcon Ângela Rossi , Carnieli Gilberto João , Roani Carlos André , Vanderlinde Regina 
Published: September 2010

AbstractWe present a method that can differentiate between the varieties of grapes and the vintages of wines and show the relationship between the grapes, the wine and the geographic location. The place of origin and its geographic and climatic characteristics were determined by the isotopic ratios, 13C/12C of the ethanol and 18O/16O of the water content of wine (wine water), for southern Brazil wines. The producing subregions of Pinto Bandeira, Vale dos Vinhedos and Nova Pádua showed differences in the temperature, rainfall and humidity conditions used for the production under microvinification conditions of Merlot and Cabernet Sauvignon varieties, in the harvests of 2005 and 2006. An isotope ratio mass spectrometer coupled to an elemental analyzer was used to measure the 13C/12C of ethanol and the 18O/16O of wine water. Regardless of the grape variety used, it was possible to determine the subregion through measurement of the δ18O values in both harvests. The altitudes of the different subregions led to statistical differences and demonstrated an influence mainly on the δ18O values of wine water. The δ18O value of wine water was determined to be more selective for the determination of the cultivation subregions than the δ13C value of the ethanol. The altitude and latitude influenced mainly the δ 18O values of wine water and the ethanol. The climatic influences are more noteworthy in distinguishing the year of the harvest than the cultivation subregion. Copyright © 2010 John Wiley & Sons, Ltd.
Characterization and identification of saponins in Achyranthes bidentata by rapid‐resolution liquid chromatography with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry
Authors: Li Yan‐Jing , Wei Huan‐Li , Qi Lian‐Wen , Chen Jun , Ren Mei‐Ting , Li Ping 
Published: September 2010

AbstractA rapid‐resolution liquid chromatography (RRLC) method coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (Q‐TOF MS/MS) has been developed for analysis of oleanane‐type triterpenoid saponins in Achyranthes bidentata. Collision‐induced dissociation techniques were used to fragment the precursor molecular ions and the resulting product ions. A retro‐Diels‐Alder rearrangement from the oleanane aglycone skeleton in the MS/MS process yielded characteristic fragment ions in positive ion mode. These characteristic ions were helpful in predicting the aglycone structure. Losses of monosaccharide sequences, presence of sugar‐chain fragment ions, and cleavage of CO2 were observed for important information on sugar types and attachment sequences. Fragmentation rules of three major groups of saponins from A. bidentata were summarized, and the possible fragmentation pathways were proposed. A total of 22 compounds including both the target and unknown oleanane‐type triterpenoid saponins were rapidly screened and predicted in the herbal extract by the developed method. The RRLC‐Q‐TOF MS/MS method has provided a powerful approach for rapid separation, target screening and structural elucidation of oleanane‐type saponins, and also opened perspectives for similar studies on other herbal medicines. Copyright © 2010 John Wiley & Sons, Ltd.
Determining the topology of virus assembly intermediates using ion mobility spectrometry–mass spectrometry
Authors: Knapman Tom W. , Morton Victoria L. , Stonehouse Nicola J. , Stockley Peter G. , Ashcroft Alison E. 
Published: September 2010

AbstractWe have combined ion mobility spectrometry–mass spectrometry with tandem mass spectrometry to characterise large, non‐covalently bound macromolecular complexes in terms of mass, shape (cross‐sectional area) and stability (dissociation) in a single experiment. The results indicate that the quaternary architecture of a complex influences its residual shape following removal of a single subunit by collision‐induced dissociation tandem mass spectrometry. Complexes whose subunits are bound to several neighbouring subunits to create a ring‐like three‐dimensional (3D) architecture undergo significant collapse upon dissociation. In contrast, subunits which have only a single neighbouring subunit within a complex retain much of their original shape upon complex dissociation. Specifically, we have determined the architecture of two transient, on‐pathway intermediates observed during in vitro viral capsid assembly. Knowledge of the mass, stoichiometry and cross‐sectional area of each viral assembly intermediate allowed us to model a range of potential structures based on the known X‐ray structure of the coat protein building blocks. Comparing the cross‐sectional areas of these potential architectures before and after dissociation provided tangible evidence for the assignment of the topologies of the complexes, which have been found to encompass both the 3‐fold and the 5‐fold symmetry axes of the final icosahedral viral shell. Such insights provide unique information about virus assembly pathways that could allow the design of anti‐viral therapeutics directed at the assembly step. This methodology can be readily applied to the structural characterisation of many other non‐covalently bound macromolecular complexes and their assembly pathways. Copyright © 2010 John Wiley & Sons, Ltd.
Quantification of deuterated bisphenol A in serum, tissues, and excreta from adult Sprague‐Dawley rats using liquid chromatography with tandem mass spectrometry
Authors: Twaddle Nathan C. , Churchwell Mona I. , Vanlandingham Michelle , Doerge Daniel R. 
Published: September 2010

AbstractBisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products, epoxy resin‐based food can liners, and paper products. The presence of BPA in urine of >90% of Americans aged 6–60 suggests ubiquitous and frequent exposure and is problematic because of the potential for endocrine disruption. The ubiquity of environmental BPA in common laboratory supplies used for sample collection, storage, and analysis greatly increases the likelihood of false positive determinations, particularly at trace levels. The current study validated using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in conjunction with deuterated BPA as the dosing material to circumvent contamination for high sensitivity quantifications in rat serum, tissues, urine, and feces. The methods described provided measurements of both estrogen receptor‐active aglycone and metabolically deactivated conjugated forms of BPA, a distinction that is critical to assessing toxicological potential. The adequacy of the described methodology was substantiated by its utility in analyzing samples from rats treated orally with a 100 µg/kg body weight dose of d6‐BPA. These results emphasize the challenges inherent in measuring BPA in biological samples and how employing stable isotope labeled dosing can facilitate pharmacokinetic studies needed to understand BPA metabolism and disposition. Such studies conducted in experimental animal models, in conjunction with properly validated human biomonitoring data, will be the basis for PBPK modeling of BPA in environmentally exposed humans. Published in 2010 by John Wiley & Sons, Ltd.
High‐performance liquid chromatography/mass spectrometric and proton nuclear magnetic resonance spectroscopic studies of the transacylation and hydrolysis of the acyl glucuronides of a series of phenylacetic acids in buffer and human plasma
Authors: Karlsson Elin S. , Johnson Caroline H. , Sarda Sunil , Iddon Lisa , Iqbal Mazhar , Meng Xiaoli , Harding John R. , Stachulski Andrew V. , Nicholson Jeremy K. , Wilson Ian D. , Lindon John C. 
Published: September 2010

AbstractThe use of high‐performance liquid chromatography/mass spectrometry (HPLC/MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy for the kinetic analysis of acyl glucuronide (AG) isomerisation and hydrolysis of the 1‐β‐O‐acyl glucuronides (1‐β‐O‐AG) of phenylacetic acid, (R)‐ and (S)‐α‐methylphenylacetic acid and α,α‐dimethylphenylacetic acid is described and compared. Each AG was incubated in both aqueous buffer, at pH 7.4, and control human plasma at 37°C. Aliquots of these incubations, taken throughout the reaction time‐course, were analysed by HPLC/MS and1H NMR spectroscopy. In buffer, transacylation reactions predominated, with relatively little hydrolysis to the free aglycone observed. In human plasma incubations the calculated rates of reaction were much faster than for buffer and, in contrast to the observations in buffer, hydrolysis to the free aglycone was a significant contributor to the overall reaction.A diagnostic analytical methodology based on differential mass spectrometric fragmentation of 1‐β‐O‐AGs compared to the 2‐, 3‐ and 4‐positional isomers, which enables selective determination of the former, was confirmed and applied. These findings show that HPLC/MS offers a viable alternative to the more commonly used NMR spectroscopic approach for the determination of the transacylation and hydrolysis reactions of these AGs, with the major advantage of having the capability to do so in a complex biological matrix such as plasma. Copyright © 2010 John Wiley & Sons, Ltd.
Cure fraction model with random effects for regional variation in cancer survival
Authors: Seppä Karri , Hakulinen Timo , Kim Hyon‐Jung , Läärä Esa 
Published: September 2010

AbstractAssessing regional differences in the survival of cancer patients is important but difficult when separate regions are small or sparsely populated. In this paper, we apply a mixture cure fraction model with random effects to cause‐specific survival data of female breast cancer patients collected by the population‐based Finnish Cancer Registry. Two sets of random effects were used to capture the regional variation in the cure fraction and in the survival of the non‐cured patients, respectively. This hierarchical model was implemented in a Bayesian framework using a Metropolis‐within‐Gibbs algorithm. To avoid poor mixing of the Markov chain, when the variance of either set of random effects was close to zero, posterior simulations were based on a parameter‐expanded model with tailor‐made proposal distributions in Metropolis steps. The random effects allowed the fitting of the cure fraction model to the sparse regional data and the estimation of the regional variation in 10‐year cause‐specific breast cancer survival with a parsimonious number of parameters. Before 1986, the capital of Finland clearly stood out from the rest, but since then all the 21 hospital districts have achieved approximately the same level of survival. Copyright © 2010 John Wiley & Sons, Ltd.
Using ancestry matching to combine family‐based and unrelated samples for genome‐wide association studies
Authors: Crossett Andrew , Kent Brian P. , Klei Lambertus , Ringquist Steven , Trucco Massimo , Roeder Kathryn , Devlin Bernie 
Published: September 2010

AbstractWe propose a method to analyze family‐based samples together with unrelated cases and controls. The method builds on the idea of matched case–control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo‐controls are constructed, based upon the transmitted and untransmitted alleles. Unrelated controls, matched by genetic ancestry, supplement the sample of pseudo‐controls; likewise unrelated cases are also paired with genetically matched controls. Within each matched stratum, the case genotype is contrasted with control/pseudo‐control genotypes via CLR, using a method we call matched‐CLR (mCLR). Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry. The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map. Once constructed, new individuals can be projected onto the ancestry map based on their genotypes. Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to construct the ancestry map. Once samples are well‐matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error. Copyright © 2010 John Wiley & Sons, Ltd.
Factors affecting power of tests for multiple binary outcomes
Authors: Mascha Edward J. , Imrey Peter B. 
Published: September 2010

AbstractFrequently in clinical studies a primary outcome is formulated from a vector of binary events. Several methods exist to assess treatment effects on multiple correlated binary outcomes, including comparing groups on the occurrence of at least one among the outcomes (‘collapsed composite’), on the count of outcomes observed per subject, on individual outcomes adjusting for multiplicity, or with multivariate tests postulating either common or distinct effects across outcomes. We focus on a 1‐df distinct effects test in which the estimated outcome‐specific treatment effects from a GEE model are simply averaged, and compare it with other methods on clinical and statistical grounds.Using a flexible method to simulate multivariate binary data, we show that the relative efficiencies of the assessed tests depend in a complex way on the magnitudes and variabilities of component incidences and treatment effects, as well as correlations among component events. While other tests are easily ‘driven’ by high‐frequency components, the average effect GEE test is not, since it averages the log odds ratios unweighted by the component frequencies. Thus, the average effect test is relatively more powerful than other tests when lower frequency components have stronger associations with a treatment or other predictor, but less powerful when higher frequency components are more strongly associated. In studies when relative effects are at least as important as absolute effects, or when lower frequency components are clinically most important, this test may be preferred. Two clinical trials are discussed and analyzed, and recommendations for practice are made. Copyright © 2010 John Wiley & Sons, Ltd.
Best combination of multiple diagnostic tests for screening purposes
Authors: Qin Jing , Zhang Biao 
Published: September 2010

AbstractIn a medical diagnostic testing problem, multiple diagnostic tests are often available in distinguishing between diseased and nondiseased subjects. Different diagnostic tests are usually sensitive to different aspects of the disease. A desirable approach is to combine multiple diagnostic tests so as to obtain an optimal composite diagnostic test with higher sensitivity and specificity that detects the presence of the disease more accurately. To accomplish this, it has been observed via signal detection theory developed in the 1950s and 1960s, that the optimal combination of different diagnostic variables (i.e. the diagnostic test results) is determined by the likelihood ratio function for the diseased and nondiseased groups. The conventional approach is to fit parametric models for the diseased and nondiseased groups separately and then to use the fitted likelihood ratio function for the best combination of test results. However, this approach is not so robust if the underlying distribution functions are misspecified. Since the optimal combination depends only on the likelihood ratio function, it would be more appropriate to model this function directly. A two‐sample semiparametric inference technique is applied to the model for the likelihood ratio function. We consider the best combination of multiple diagnostic tests, and study semiparametric likelihood estimation of the optimal receiver operating characteristic curve and the area under the curve. We present a bootstrap procedure along with some results on simulation and on analysis of two real data sets. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of a Pillared Graphene Nanostructure: A Counterpart of Three‐Dimensional Carbon Architectures
Authors: Paul Rajat Kanti , Ghazinejad Maziar , Penchev Miroslav , Lin Jian , Ozkan Mihrimah , Ozkan Cengiz Sinan 
Published: September 2010

AbstractGraphene is a single sheet of carbon atoms with outstanding electrical and physical properties and is being exploited for applications in electronics, sensors, photovoltaics, and energy storage. A novel 3D architecture called a pillared graphene nanostructure (PGN) is a combination of two allotropes of carbon, including graphene and carbon nanotubes. A one‐step chemical vapor deposition process for large‐area PGN fabrication via a combination of surface catalysis and in situ vapor–liquid–solid mechanisms is described. A process by which PGN layers can be transferred onto arbitrary substrates while keeping the 3D architecture intact is also described. Single and multilayer stacked PGNs are envisioned for future ultralarge and tunable surface‐area applications in hydrogen storage and supercapacitors.