bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of dielectric barrier discharge ionization mass spectrometry for pesticide testing: a comparison with atmospheric pressure chemical ionization and electrospray ionization
Authors: Gilbert‐López Bienvenida , Geltenpoth Helma , Meyer Cordula , Michels Antje , Hayen Heiko , Molina‐Díaz Antonio , García‐Reyes Juan F. , Franzke Joachim 
Published: December 2012

RATIONALEThe present study reports on the evaluation of dielectric barrier discharge microplasma ionization (DBDI) for liquid chromatography/high resolution mass spectrometry (LC/HRMS) analyses of pesticide residues in fruit and vegetables. Ionization, fragmentation, analytical performance and matrix effects displayed by LC/DBDI‐MS were critically evaluated and compared with both atmospheric pressure chemical ionization (APCI) and electrospray (ESI), using a set of over 40 representative multiclass pesticides.METHODSSample preparation was accomplished using standard QuEChERS procedure and the identification and quantitation of the pesticides tested accomplished by means of LC/MS with a hybrid linear quadrupole ion trap (LIT)‐Fourier transform ion cyclotron resonance (FTICR) mass spectrometer operated in full‐scan positive ion mode using DBDI, APCI and ESI sources.RESULTSThe developed LC/DBDI‐MS method allowed the screening of 43 pesticides in three different vegetable matrices: apple, orange and tomato. Minor matrix effects (i.e. signal suppression or enhancement ≤20%) were observed in most of the studied compounds: 95%, 70% and 81% of the studied compounds showed minor matrix effects in extracts of apple, orange and tomato, respectively. The results of the analysis of spiked orange extracts showed that the sensitivity obtained with LC/DBDI‐MS is appropriate for multi‐residue analysis of pesticide residues in fruit and vegetable samples. The limits of quantitation (LOQs) obtained for most of the studied pesticides were in compliance with the European Regulation 396/2005 (and subsequent updates) on food commodities (default maximum residue level of 10 µg kg–1).CONCLUSIONSComparative studies with commercial sources demonstrate the suitability of DBDI as an ionization technique for residue analysis, because of the combination of the following two advantages: (1) the use of DBDI provides minimized matrix effects compared with APCI, and (2) improved the detection – in terms of sensitivity – of selected compounds that are not easily ionized by ESI, such as parathion. Copyright © 2012 John Wiley & Sons, Ltd.
Surface‐activated chemical ionization–electrospray mass spectrometry in the analysis of urinary thiodiglycolic acid
Authors: Puccio Giovanni , Brambilla Paolo , Conti Matteo , Bartolini Desirée , Noonan Douglas , Albini Adriana 
Published: December 2012

RATIONALEThiodiglycolic acid (TDGA) is a urinary metabolite of the oxazaphosphorine class of chemotherapeutics, in particular of ifosfamide. Ifosfamide metabolism generates chloroacetaldehyde (CAA), a toxic compound associated with neurotoxicity, nephrotoxicity, urotoxicity and cardiotoxicity. CAA, in turn, interacts with cellular thiol groups leading to GSH depletion, cell death and generation of thiodiglycolic acid (TDGA), as a final product. TDGA is mainly excreted in the urine. The ability to accurately measure TDGA in urine, therefore, will be a useful way of monitoring exposure to ifosfamide during chemotherapy.METHODSTDGA in urine samples was measured with liquid chromatography coupled to mass spectrometry (LC/MS) by means of a novel Surface‐Activated Chemical Ionization–Electrospray (SACI–ESI) or a classical ESI ion source alone.RESULTSThe SACI–ESI and ESI alone based methods for analysis of urinary TDGA were optimized and compared. A strong reduction in matrix effect together with enhanced quantification performances was obtained with the SACI–ESI when compared with ESI. In particular, an increase in quantification precision (from 85 to 95%) and accuracy (from 59 to 90%) were observed, which allowed for optimal detection of TDGA.CONCLUSIONSThe LC/SACI–ESI‐MS approach provides a very sensitive and quantitative method for the analysis of TDGA. Thanks to the enhancement in sensitivity and matrix effect reduction, the SACI–ESI source enables the use of a relatively low‐cost ion‐trap mass spectrometer in the analysis of this toxicity biomarker in urine. Due to these characteristics, this approach would constitute an invaluable tool in the clinical laboratory, for measuring TDGA and other toxicity related biomarkers of chemotherapy with proper sensitivity and accuracy. Copyright © 2012 John Wiley & Sons, Ltd.
Improved ruggedness of an ion‐pairing liquid chromatography/tandem mass spectrometry assay for the quantitative analysis of the triphosphate metabolite of a nucleoside reverse transcriptase inhibitor in peripheral blood mononuclear cells
Authors: Zhao Yue , Liu Guowen , Liu Yifei , Yuan Long , Hawthorne Dara , Shen Jim X. , Guha Mausumee , Aubry Anne 
Published: December 2012

RATIONALENucleotide analogs are highly polar and ionic, which impose great challenges on bioanalysis. Ion‐pairing liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the predominant reported approach for such compounds. Assay ruggedness of ion‐pairing LC/MS/MS methods was often a challenge due to the potential contamination of the ion source of the mass spectrometer and LC column performance deterioration caused by ion‐pairing reagents.METHODSAn ion‐pairing reagent was only added to the reconstitution solution to minimize its exposure to the MS ion source. To achieve optimum sensitivity, high pH mobile phases and negative ion ESI were needed for the LC/MS/MS method. However, high pH mobile phases led to the accumulation of ion‐pairing reagent on the analytical column, which was washed off with an acidic solution to restore the column performance. In addition, isopropanol was used as a mobile phase modifier to improve peak shape and sensitivity.RESULTSThe limit of detection was established at 1.0 ng/mL in the cell lysate. The calibration curve showed good linearity over the range of 1.0 to 100 ng/mL. The overall accuracy was no less than 87.7% based on four levels of quality control samples. Inter‐run precision and intra‐run precision across four analytical runs for low, geometric, medium and high QCs were less than 12.9.CONCLUSIONSBy identifying and addressing the root cause of the assay ruggedness problem, we have developed a rugged ion‐pairing LC/MS/MS method for a triphosphate (TP) metabolite of BMS‐986001 in peripheral blood mononuclear cells. The new method overcame challenges such as a rapid deterioration of the peak shape, increased carryover and extremely poor column life. The peak shape was well maintained throughout multiple analytical runs. This method has been successfully applied to a toxicology study in cynomolgus monkey. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of various endogenous and artefact modifications on large‐scale proteomics analysis
Authors: Bienvenut Willy V. , Sumpton David , Lilla Sergio , Martinez Aude , Meinnel Thierry , Giglione Carmela 
Published: December 2012

RATIONALESome large‐scale proteomics studies in which strong cation exchange chromatography has been applied are used to determine proteomes and post‐translational modification dynamics. Although such datasets favour the characterisation of thousands of modified peptides, e.g., phosphorylated and N‐α‐acetylated, a large fraction of the acquired spectra remain unexplained by standard proteomics approaches. Thus, advanced data processing allows characterisation of a significant part of these unassigned spectra.METHODSOur recent investigation of the N‐α‐acetylation status of plant proteins gave a dataset of choice to investigate further the in‐depth characterisation of peptide modifications using Mascot tools associated with relevant validation processes. Such an approach allows to target frequently occurring modifications such as methionine oxidation, phosphorylation or N‐α‐acetylation, but also the less usual peptide cationisation. Finally, this dataset offers the unique opportunity to determine the overall influence of some of these modifications on the identification score.RESULTSAlthough methionine oxidation has no influence and tends to favour the characterisation of protein N‐terminal peptides, peptide alkalinisation shows an adverse effect on peptide average score. Nevertheless, peptide cationisation appears to favour the characterisation of protein C‐terminal peptides with a limited to no direct influence on the identification score. Unexpectedly, our investigation reveals the unfortunate combination of the molecular weight of N‐α‐acetylation and potassium cation that mimics the mass increment of a phosphorylation group.CONCLUSIONSSince these characterisations rely upon computational treatment associated with statistical validation approaches such as 'False discovery rates' calculation or post‐translational modification position validation, our investigation highlights the limitation of such treatment which is biased by the initial searched hypotheses. Copyright © 2012 John Wiley & Sons, Ltd.
Fragmentation characteristics and isomeric differentiation of flavonol O‐rhamnosides using negative ion electrospray ionization tandem mass spectrometry
Authors: Ablajan Keyume , Tuoheti Anagu 
Published: December 2012

RATIONALEFlavonoids exhibit a wide range of biological activities. The differentiation and structural characterization of the flavonol O‐rhamnosides and their isomers are important research topics. Electrospray ionization tandem mass spectrometry (ESI‐MSn) is an indispensable tool and has become an efficient method for the identification of bioactive natural products.METHODSNegative ion ESI‐MSn was used to characterize and differentiate flavonol O‐rhamnosides and their isomeric compounds. The collision energies in collision‐induced dissociation were varied to optimize the structural information.RESULTSFlavonol 7‐O‐rhamnosides containing either a hydroxyl or a methoxyl group at the C‐8 position clearly differed from their isomeric compounds, such as the flavonol 3‐O‐rhamnosides, in the product ion spectra of the [M–H]– ions. The differences in the locations of the glycosyl group and OCH3 group resulted in a significant change in the relative abundances of the Y0– and [Y0–H]–• ions, and the formation of some characteristic ions, such as 1,3A0– and [1,3A0–CH3]–•.CONCLUSIONSAn efficient ESI‐MSn method for the structural identification and isomeric differentiation of flavonol O‐rhamnosides was developed. The differences in the glycosyl type, and the glycosylation and methoxylation positions in the structures of isomeric flavonoids, can be determined using (–)ESI‐MSn spectra. The formation and relative abundances of [Y0–H]–• and Y0– ions, as well as the comparison of some diagnostic ions, are vital in the differentiation of isomeric flavonoids. These results have practical applications in the rapid identification of flavonol O‐rhamnosides present in crude bioactive extracts. Copyright © 2012 John Wiley & Sons, Ltd.
Bridging across cognitive training and brain plasticity: a neurally inspired computational model of interactive skill learning
Authors: Fu Wai‐Tat , Lee Hyunkyu , Boot Walter R. , Kramer Arthur F. 
Published: December 2012

AbstractThis article reviews recent empirical and brain imaging data on effects of cognitive training methods on complex interactive skill learning, and presents a neurally inspired computational model that characterizes the effects of these training methods. In particular, the article focuses on research that shows that variable priority training (VPT), which requires learners to shift their priorities to different task components during training, often leads to better acquisition and retention of skills than fixed priority training (FPT). However, there is only weak evidence that shows that VPT can enhance transfer of complex interactive skills to untrained situations. Brain imaging studies show that VPT leads to significantly lower activations and a higher reduction of activities in attentional control areas after training than FPT. Research also shows that the volume of the striatum predicts the learning effects, but only in VPT. The computational model, developed based on learning mechanisms at the neural level, bridges across the empirical and the braining imaging results by explaining the effects of VPT and FPT at both the behavioral and neural levels. The results were discussed in the context of previous findings on cognitive training.WIREs Cogn Sci2013, 4:225–236. doi: 10.1002/wcs.1214This article is categorized under:Psychology > Learning
P2Y receptors in neurogenesis
Authors: Illes Peter , Messemer Nanette , Rubini Patrizia 
Published: December 2012

AbstractG protein‐coupled P2Y receptors (Rs) regulate the function of embryonic and adult neural precursor cells (NPCs) which have the capacity to regenerate and give rise to cells belonging to all three major linages of the nervous system: neurons, oligodendrocytes and astrocytes. The presence of mRNA and protein for various P2YRs have been demonstrated by RT‐PCR, immunohistochemistry and western‐blotting in NPCs. In agreement with the sensitivity of different subtypes of P2YRs to purine and pyrimidine nucleotides, the ATP‐responsive P2Y1R and the ATP/UTP‐responsive P2Y2R both released intracellular Ca2+ from its storage sites in NPCs. Nucleotide‐induced Ca2+ oscillations have a signaling function in NPC syncitia and appear to be involved in cellular proliferation. Two further NPC functions regulated by P2Y receptors are migration and differentiation, especially through P2Y1R‐activation, although P2Y2Rs may also participate. WIREs Membr Transp Signal 2013, 2:43–48. doi: 10.1002/wmts.76For further resources related to this article, please visit the WIREs website.
Provenance of Pleistocene Rhine River Middle Terrace sands between the Swiss–German border and Cologne based on U–Pb detrital zircon ages
Authors: Krippner Anne , Bahlburg Heinrich 
Published: December 2012

Abstract
Detrital zircon U–Pb age distributions derived from samples representing ancient or relatively young large-scale continental drainage networks are commonly taken to reflect the geochronological evolution of the tapped continental area. Here, we present detrital zircon U–Pb ages and associated heavy mineral data from Pleistocene Rhine River Middle Terrace sands and equivalents between the Swiss–German border and Cologne in order to test the commonly assumed Alpine provenance of the material. Samples from eight localities were analyzed for their heavy mineral assemblages. Detrital zircon U–Pb ages were determined by laser ablation inductively coupled mass spectrometry on selected samples from five locations along the Rhine River. The zircon age populations of all samples show a similar distribution, their main peaks being between 300 and 500 Ma. Minor age populations are recognized at 570 and 1,070 Ma. The 300–400 Ma maximum reflects the Variscan basement drained by or recycled into the Rhine River and its tributaries. The 400–500 Ma peak with predominantly Early Silurian ages points to Baltica or to the mid-German crystalline rise as original sources. One distinct peak at c. 570 Ma probably represents input from Cadomian terranes. The Precambrian U–Pb ages are compatible with derivation from sources in Baltica and in northern Gondwana. The heavy mineral populations of Middle Terrace sands and equivalents are characterized to a variable extend by garnet, epidote, and green hornblende. This association is often referred to as the Alpine spectrum and is considered to be indicative of an Alpine provenance. However, hornblende, epidote, and garnet are dominant heavy minerals of collisional orogens in general and may also be derived from Variscan and Caledonian units or from intermittent storage units. A remarkable feature of the detrital zircon age distribution in the Rhine River sediments from the Swiss–German border to Cologne is the absence of ages younger than 200 Ma and in particular of any ages reflecting the Alpine orogeny between c. 100 and 35 Ma. Sediments from rivers draining the equally collisional Himalaya orogen contain detrital zircons as young as 20 Ma. Our results question the assumption that Pleistocene Rhine River sediments were directly derived from the Alps. The lag time between the formation and deposition age of the youngest zircon in the studied Pleistocene Rhine River deposits is 200 Ma. Together with the absence of Alpine zircon ages, this stresses that detrital zircon age data from ancient sedimentary units found in poorly understood tectonic or paleogeographic settings need to be interpreted with great care, one could miss an entire orogenic cycle.
Short rigid scope and stereo‐scope designed specifically for open abdominal navigation surgery: clinical application for hepatobiliary and pancreatic surgery
Authors: Onda Shinji , Okamoto Tomoyoshi , Kanehira Masaru , Fujioka Shuichi , Suzuki Naoki , Hattori Asaki , Yanaga Katsuhiko 
Published: December 2012

AbstractBackgroundWe have reported the utility of an image display system using augmented reality (AR) technology in hepatobiliary surgery under laparotomy. Among several procedures, we herein report a system using a novel short rigid scope and stereo‐scope, both designed specifically for open abdominal navigation surgery, and their clinical application for hepatobiliary and pancreatic surgery.MethodsThe 3D reconstructed images were obtained from preoperative computed tomography data. In our specialized operating room, after paired‐point matching registration, the reconstructed images are overlaid onto the operative field images captured by the short rigid scopes. The scopes, which are compact and sterilizable, can be used in the operative field. The stereo‐scope provides depth information. Eight patients underwent operations using this system, including hepatectomy in two, distal pancreatectomy in three, and pancreaticoduodenectomy in three patients. The stereo‐scope was used in five patients.ResultsAll eight operations were performed safely using the novel short rigid scopes, and stereo images were acquired in all five patients for whom the stereo‐scope was used. The scopes were user friendly, and the intraoperative time requirement for our system was reduced compared with the conventional method.ConclusionsThe novel short rigid scope and stereo‐scope seem to be suitable for clinical use in open abdominal navigation surgery. In hepatobiliary and pancreatic surgery, our novel system may improve the safety, accuracy and efficiency of operations.
Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor
Authors: Ito Tetsuhide , Okusaka Takuji , Nishida Toshirou , Yamao Kenji , Igarashi Hisato , Morizane Chigusa , Kondo Shunsuke , Mizuno Nobumasa , Hara Kazuo , Sawaki Akira , Hashigaki Satoshi , Kimura Nobuyuki , Murakami Mami , Ohki Emiko , Chao Richard C. , Imamura Masayuki 
Published: December 2012

SummaryBackground. Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy. Patients and methods. This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] ≥24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers. Results. Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43–94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21–79). PFS probability was 91 % (95 % CI, 54–99) at 6 months and 71 % (95 % CI, 34–90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n = 10), hand–foot syndrome and hypertension (both n = 8), fatigue and headache (both n = 7), and neutropenia (n = 6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in chromogranin A levels. Conclusions. Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib.
Molecular Ion‐Independent Quantification of Polar Glycerolipid Classes in Marine Plankton Using Triple Quadrupole MS
Authors: Popendorf Kimberly J. , Fredricks Helen F. , Van Mooy Benjamin A. S. 
Published: December 2012

AbstractPolar glycerolipids are a diverse family of lipid molecules that form the bulk of bacterial and eukaryotic microbial membranes. The earth and ocean sciences has a long history of using fatty acids as biomarkers for microbes, but have only recently begun to examine the intact polar lipids from which they are derived. Current analytical approaches rely on laboriously quantifying the molecular ions of each of these species independently. Thus, we saw a need for a method for quantifying polar glycerolipid classes that was: (i) selective for individual classes, (ii) inclusive of all species within a class, (iii) independent of foreknowledge of the molecular ions of the polar glycerolipid, and (iv) amenable to automated, high‐throughput data analysis methods. Our new HPLC‐electrospray‐ionization triple‐quadrupole MS (HPLC‐ESI‐TQMS) method can be applied to quantify the nine major classes of polar glycerolipid in planktonic communities: the phospholipids phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine; the glycolipids monoglycosyldiacylglycerol, diglycosyldiacylglycerol and sulfoquinovosyldiacylglycerol; and the betaine lipids diacylglyceryl trimethyl homoserine, diacylglyceryl hydroxymethyl trimethyl‐β‐alanine, and diacylglyceryl carboxyhydroxymethylcholine. The analyses rely on neutral loss and parent ion scan events that yield one chromatogram for each class of polar glycerolipid, simplifying downstream analysis and increasing sample throughput. The efficacy of the method was demonstrated by analyzing plankton community samples from a variety of marine environments.
Simulations to Assess Phase II Noninferiority Trials of Different Doses of Capecitabine in Combination With Docetaxel for Metastatic Breast Cancer
Authors: Bruno R , Lindbom L , Schaedeli Stark F , Chanu P , Gilberg F , Frey N , Claret L 
Published: December 2012

A phase II trial in metastatic breast cancer (MBC) (NO16853) failed to show noninferiority (progression‐free survival, PFS) of capecitabine 825 mg/m2 plus docetaxel 75 mg/m2 to the registered capecitabine dose of 1,250 mg/m2 plus docetaxel 75 mg/m2. We developed a modeling framework based on NO16853 and the pivotal phase III MBC study, SO14999, to characterize the link between capecitabine dose, tumor growth, PFS, and survival to simulate response to a range of capecitabine doses and determine a minimum capecitabine dose noninferior to 1,250 mg/m2. Simulation showed NO16853 had little power to demonstrate noninferiority (69%). The power reached 80% with a 1,000 mg/m2 starting dose and an increased number of PFS events. A starting dose of 1,000 mg/m2 could be established as noninferior in terms of efficacy to the registered dose in the second‐line MBC setting, with a potentially improved safety, in line with medical practice.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e19; doi:10.1038/psp.2012.20; advance online publication 26 December 2012