bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the linear dynamic range in quantitative high performance liquid chromatography/tandem mass spectrometry by the use of multiple product ions
Authors: Curtis Michael A. , Matassa Luca C. , Demers Roger , Fegan Katrina 
Published: August 2002

AbstractA strategy for expanding the linear working range in bioanalysis using quantitative high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) is presented. The strategy involves monitoring multiple product ions. Herein we demonstrate the strategy on a rat plasma assay for a proprietary experimental drug where the linear range is expanded from 2 to 4 orders of magnitude. A primary sensitive ion was monitored to obtain a high sensitivity range calibration curve (0.400 to 100 ng/mL) while a less sensitive secondary ion was monitored to obtain a low sensitivity range calibration curve (90.0 to 4000 ng/mL). Each calibration curve gave acceptable linearity (r >0.990). Quality control samples at low, mid and high levels within each calibration curve demonstrated acceptable precision and accuracy (within 20% for all levels). The technique was successfully applied to rat pre‐clinical sample analysis. Copyright © 2001 John Wiley & Sons, Ltd.
Genotyping single nucleotide polymorphisms using intact polymerase chain reaction products by electrospray quadrupole mass spectrometry
Authors: Walters James J. , Muhammad Warees , Fox Karen F. , Fox Alvin , Xie Dawen , Creek Kim E. , Pirisi Lucia 
Published: August 2002

AbstractBoth single nucleotide polymorphisms (SNPs) and mutations are commonly observed in the gene encoding the tumor suppressor protein, p53. SNPs occur at specific locations within genes whereas mutations may be distributed across large regions of genes. When determining nucleotide differences, mass spectrometry is the only method other than Sanger sequencing which offers direct structural information. Electrospray ionization (ESI) quadrupole mass spectrometry (MS) analysis of intact polymerase chain reaction (PCR) products was performed following a simple purification and on‐line heating to limit ion adduction. The PCR products were amplified directly from genomic DNA rather than plasmids, as in our previous work. Two known polymorphisms of the p53 gene were genotyped. A cytosine (C) or guanine (G) transversion, designated C ↔ G (G ↔ C on the opposite strand), were each detected by a 40.0 Da change upon ESI quadrupole MS analysis. Using known PCR products as standards, the genotypes determined for 10 human samples corresponded with restriction fragment length polymorphism (RFLP) analysis. Cytosine/thymine (T) transitions, designated C ↔ T (G ↔ A on the opposite strand), were also genotyped by ESI‐MS. This SNP is discriminated by a 15.0 Da change on one strand (C ↔ T) and a 16.0 Da change on the other (G ↔ A). Appropriate sample preparation and instrumental configuration (including heated sample inlet syringe and MS source), to limit adducts, are both vital for successful ESI quadrupole MS analysis of intact PCR products. Copyright © 2001 John Wiley & Sons, Ltd.
Fragmentation of N‐oxides (deoxygenation) in atmospheric pressure ionization: Investigation of the activation process
Authors: Tong Wei , Chowdhury Swapan K. , Chen Jin‐Chang , Zhong Ruyun , Alton Kevin B. , Patrick James E. 
Published: August 2002

AbstractThe diagnostic fragmentation of N‐oxides resulting from loss of the oxygen atom (MH+ → MH+‐O) in electrospray and atmospheric pressure chemical ionization (APCI) mass spectra was investigated. When the temperature of the heated capillary tube was elevated, the ratio of the intensity of the [MH+ − 16] fragment to the precursor ion (MH+) increased. This ‘deoxygenation’ process was associated with thermal activation and did not result from collisional activation in the desolvation region of the API source. Although the extent of ‘deoxygenation’ is compound‐dependent, it can provide evidence for the presence of an N‐oxide in a sample and can be used to distinguish N‐oxides from hydroxylated metabolites (Ramanathan et al. Anal. Chem. 2000; 72: 1352). To demonstrate the practical application of thermal fragmentation of N‐oxides, liquid chromatography (LC)/APCI‐MS was used to distinguish an N‐oxide drug from its hydroxylated metabolite in an unprocessed rat urine sample, despite the fact that the drug and its metabolite were not fully resolved by HPLC. Copyright © 2001 John Wiley & Sons, Ltd.
Non‐covalent binding of endogenous ligands to recombinant cellular retinol‐binding proteins studied by mass spectrometric techniques
Authors: Elviri L. , Zagnoni I. , Careri M. , Cavazzini D. , Rossi G. L. 
Published: August 2002

AbstractRecent developments in mass spectrometry have demonstrated the capability of this technique to transfer non‐covalent protein complexes, involving low and high molecular weight ligands, from a condensed state to the gas phase. In this work, electrospray mass spectrometry with a quadrupole analyzer (ES‐MS) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) were used to analyze the non‐covalent association between recombinant rat cellular retinol‐binding protein type‐I (CRBP) with its specific ligand, all‐trans retinol (vitamin A), and with fatty acids. Under denaturing conditions, MALDI‐TOFMS and ES‐MS techniques allowed determination of the molecular weight of apo‐CRBP with good accuracy (<0.01%) and to identify a protein fraction (∼20%) retaining the initial methionine. By adding saturating amounts of vitamin A, ES‐MS studies on the protein in the holo‐form under native conditions allowed detection of retinol bound within the cavity together with water molecules, as expected from its crystal structure. ES mass spectra of CRBP in the native state were also recorded under non‐denaturing conditions, with the aim to study non‐covalent interactions between CRBP and non‐specific ligands such as fatty acids, bound to the protein as a result of expression in various strains of E. coli grown in different media. Since ES mass spectra do not elucidate which species interact with the protein, in order to investigate the ligands possibly retained in the active site of recombinant CRBP, liquid chromatography/ES‐tandem mass spectrometry was used. In particular, this technique was applied to identify and quantify fatty acids bound to CRBP. Quantitative data indicated the presence of a few fatty acids at a total concentration lower than 2% of that of the protein. Similar findings were observed for the homolog rat cellular retinol‐binding protein type‐II, demonstrating the high degree of purity and homogeneity of apo‐CRBP preparations derived from gene expression. Copyright © 2001 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery process
Authors: Tiller Philip R. , Romanyshyn Leslie A. 
Published: August 2002

AbstractThroughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra‐fast gradient chromatographic methods. Typical ultra‐fast high‐performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full‐linear gradients over 1–2 min at very high flow rates (1.5–2 mL/min) on very short HPLC columns (2 × 20 mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn‐around time. Some examples of this approach are discussed in further detail. Copyright © 2002 John Wiley & Sons, Ltd.
Clinical features of variant Creutzfeldt‐Jakob disease
Authors: Henry Colm , Knight Richard 
Published: August 2002

AbstractSince 1996, over one hundred cases of variant Creutzfeldt‐Jakob disease have appeared, mostly in the United Kingdom. In this review, we summarise the major clinical features of this progressive neurodegenerative condition and compare them with those of sporadic Creutzfeldt‐Jakob disease. We emphasise the young age (median 26 years) at presentation and the dominant psychiatric/behavioural features, particularly depression. Sensory symptoms are present initially in half the cases and florid psychiatric symptoms, such as delusions or hallucinations, are also common. Given these symptoms, many patients present in clinical practice initially to a psychiatrist but are referred to neurologists when neurological signs become apparent. Although the definitive diagnosis remains neuropathological, a confident pre‐mortem diagnosis is now possible when the ‘pulvinar sign’ is seen on magnetic resonance imaging studies. Copyright © 2002 John Wiley & Sons, Ltd.
Rerum cognoscere causas: Part II—Opportunities generated by the agency/structure debate and suggestions for clarifying the social theoretic position of system dynamics
Authors: Lane David C. 
Published: August 2002

AbstractThis is the second half of a two‐part paper dealing with the social theoretic assumptions underlying system dynamics. In the first half it was concluded that analysing system dynamics using traditional, paradigm‐based social theories is highly problematic. An innovative and potentially fruitful resolution is now proposed to these problems. In the first section it is argued that in order to find an appropriate social theoretic home for system dynamics it is necessary to look to a key exchange in contemporary social science: the agency/structure debate. This debate aims to move beyond both the theories based only on the actions of individual human agents, and those theories that emphasise only structural influences. Emerging from this debate are various theories that instead aim to unite the human agent view of the social realm with views that concentrate solely on system structure. It is argued that system dynamics is best viewed as being implicitly grounded in such theories. The main conclusion is therefore that system dynamics can contribute to an important part of social thinking by providing a formal approach for explicating social mechanisms. This conclusion is of general significance for system dynamics. However, the over‐arching aim of the two‐part paper is to increase the understanding of system dynamics in related disciplines. Four suggestions are therefore offered for how the system dynamics method might be extended further into the social sciences. It is argued that, presented in the right way, the formal yet contingent feedback causality thinking of system dynamics should diffuse widely in the social sciences and make a distinctive and important contribution to them.
Felix qui potuit rerum cognoscere causas

‘Happy is he who comes to know the causes of things’

Virgil—Georgics, Book II, line 490. 29 BCE
Copyright © 2001 John Wiley & Sons, Ltd.
Mechanisms for pitting corrosion in alloy N04400 as revealed by imaging XPS, ToF‐SIMS and low‐voltage SEM
Authors: Francis J. T. , McIntyre N. S. , Davidson R. D. , Ramamurthy S. , Brennenstühl A. M. , McBride A. , Roberts A. 
Published: August 2002

AbstractImaging XPS has been used to determine the distributional patterns of corrosion products of different chemistry on a nickel–copper alloy surface that has been subjected to pitting corrosion. Separate regions within corrosion pits can be identified with chemical processes that are suggested to be anodic and cathodic in nature. The anodic processes are indicated by a thin layer of cuprous oxide covering the base alloy, suggesting the preferential dissolution of nickel. Areas undergoing a cathodic process are indicated by the deposition of nickel as an oxide or hydroxide. Adjacent regions also were studied by XPS and characterized further by low‐voltage SEM/energy‐dispersive x‐ray imaging and time‐of‐flight SIMS techniques to obtain confirmatory and complementary information. Typically, the anodic and cathodic areas were tens of microns in size. Copyright © 2002 John Wiley & Sons, Ltd.
Interaction of a polycrystalline silver powder with ozone
Authors: Waterhouse G. I. N. , Bowmaker G. A. , Metson J. B. 
Published: August 2002

AbstractThe interaction of a polycrystalline silver powder with ozone (5 mol.% O3 in O2) was investigated over the temperature range 300–923 K. Silver powder samples were reacted with ozone for 30 min at specified temperatures in this range. All experiments were performed at atmospheric pressure. Following treatment, samples were cooled rapidly to room temperature under a nitrogen gas purge and then characterized by scanning electron microscopy, powder x‐ray diffraction, Raman spectroscopy and x‐ray photoelectron spectroscopy. The morphology, structure and chemical composition of the oxide products formed at different reaction temperatures were examined. The silver powder blackened immediately upon contact with the reaction gas mixture at 300 K, due to the formation of silver (I) oxide (Ag2O). After reaction with O3 for 30 min at 300 K, a mixed‐oxide phase comprised of Ag2O and monoclinic silver (I, III) oxide (AgO) was formed. The AgO was formed at the gas/oxide interface via the oxidation of Ag2O. A tetragonal AgO polymorph was formed when the silver powder was reacted with ozone at 473 K. The only product of silver oxidation by O3 at 673 K was Ag2O, which remained stable in the reaction gas to temperatures in excess of 773 K. The silver powder was not oxidized by ozone at 923 K, although the powder did sinter extensively during the treatment. The experimental data presented are in good accord with available thermodynamic data pertaining to the thermal stability of Ag2O and AgO in ozonized oxygen at atmospheric pressure. Copyright © 2002 John Wiley & Sons, Ltd.
Maximally selected measures of evidence of disease clusters
Authors: Burr Tom L. 
Published: August 2002

AbstractIt is now common to read reports such as ‘city A has a childhood cancer rate 30 per cent higher than the national average’. Because the details about how the data was examined can greatly impact the conclusions, the epidemiologist then wants to know more information, such as ‘over what time period’ and ‘how many other cancer types were examined’. For example, city A might have calculated cancer rates for many age groups within different regions of the city over many time intervals, but reported only the highest cancer rate discovered in a particular group. We will refer to such selective reporting as ‘maximally selecting measures of evidence of disease clustering’, or less formally as ‘fishing for statistical significance’. The objective of this paper is to study the behaviour of maximally selected statistics for measuring the extent of clustering in disease outbreaks. The original data is the time and location of each reported case of the disease. In some cases we are only given aggregates of the original data, such as the number of cases during a time period over a given region. We introduce new and review existing methods for correcting for the effect of making maximal selections in disease cluster detection. We consider three main cases with examples. We demonstrate via simulation and analytical approximations that some types of ‘fishing’ are simple to correct for while others are not. Copyright © 2001 John Wiley & Sons, Ltd.
The maintenance implications of the customization of ERP software
Authors: Light Ben 
Published: August 2002

AbstractEnterprise resource planning (ERP) software is a dominant approach for dealing with legacy information system problems. In order to avoid invalidating maintenance and development support from the ERP vendor, most organizations reengineer their business processes in line with those implicit within the software. Regardless, some customization is typically required. This paper presents two case studies of ERP projects where customizations have been performed. The case analysis suggests that while customizations can give true organizational benefits, careful consideration is required to determine whether a customization is viable given its potential impact upon future maintenance. Copyright © 2001 John Wiley & Sons, Ltd.
Dealing with the complexity of business systems architecting
Authors: Biemans F.P.M. , Lankhorst M.M. , Teeuw W.B. , van de Wetering R.G. 
Published: August 2002

AbstractEngineers are trained to design systems such as bridges, computers, and aircraft in a well‐structured manner. However, the design of business processes has not yet matured to this level. We argue that the complexity of business processes is the major cause. In this paper, we investigate the causes of this complexity, and provide heuristics to master this complexity. Business process “architecting,” the high‐level, functional design of business processes, is more an art than a science. Consequently, experience is very important. The heuristics we provide are based on an analysis of the reasons why business process architecting is so complex as well as our experience resulting from the Testbed project, a cooperative project of industry and research organizations. We conclude by discussing some basic requirements for modeling concepts and methods. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 118–133, 2001
Interaction‐based design tables for transfer beams supporting in‐plane loaded shear walls
Authors: Kuang J. S. , Li Shubin 
Published: August 2002

AbstractThe analysis and behaviour of transfer beams that support in‐plane loaded shear walls have been receiving added emphasis owing to their importance in connection with the design of tall buildings. In this paper, analysis and structural behaviour of transfer beams supporting in‐plane loaded shear walls are presented, where emphasis is placed on the interaction between the transfer beam and the supported shear wall. The interaction effect is shown to cause significant stress re‐distributions both in the transfer beam and in the shear wall within an interactive zone. Parameters that significantly influence the structural behaviour and force transfer mechanism are also highlighted. Based on finite element analysis, interaction‐based design tables are constructed and presented for the design of the transfer beam–shear wall system, which is represented by an equivalent portal frame. The design tables have been shown to provide practising engineers a very simple and efficient, yet accurate, means of analysis of the internal forces of the transfer beams and the support columns. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of folate supplementation on the risk of spontaneous and induced neural tube defects in Splotch mice
Authors: Gefrides Lisa A. , Bennett Gregory D. , Finnell Richard H. 
Published: August 2002

AbstractBackgroundNeural tube defects (NTDs) are among the most common human congenital malformations. Although clinical investigations have reported that periconceptional folic acid supplementation can reduce the occurrence of these defects, its mechanism remains unknown. Therefore, the murine mutant Splotch, which has a high incidence of spontaneous NTDs, along with the inbred strains SWV and LM/Bc, were used to investigate the relationship between folate and NTDs.MethodsTo investigate whether folates could reduce spontaneous NTDs, heterozygous Splotch dams (+/Sp) were treated with either folate or folinic acid throughout neurulation, gestational day (GD) 6.5 to 10.5. On GD 18.5 the dams were sacrificed and the fetuses examined for any neural tube defects. Subsequently, Sp/+ dams were treated with arsenic while receiving either a folate or folinic acid supplementation. Similar experiments were performed in the LM/Bc and SWV strains.ResultsNeither folate nor folinic acid supplements reduced the frequency of spontaneous NTDs in the embryos from Splotch heterozygote crosses. Arsenic increased the frequency of NTDs and embryonic death in the Splotch, LM/Bc and SWV litters and folinic acid failed to ameliorate the teratogenic effect of this metal. A folate supplement given to arsenic‐treated dams proved to be maternally lethal in all three strains.ConclusionsSplotch embryos were not protected from either spontaneous or arsenic‐induced NTDs by folinic or folic acid supplementation. Furthermore, folinic acid supplements did not reduce the incidence of arsenic‐induced NTDs in either the LM/Bc or SWV litters. Teratology 65:63–69, 2002. © 2002 Wiley‐Liss, Inc.
Effect of prenatal exposure to anticonvulsant drugs on dermal ridge patterns of fingers
Authors: Bokhari Aqiba , Coull Brent A. , Holmes Lewis B. 
Published: August 2002

AbstractBackgroundAn altered frequency of specific dermal ridge patterns on fingertips, such as an increased number of arches, has been observed in children exposed in utero to anticonvulsants and other teratogens. Asymmetry of the distribution of dermal ridge patterns has been attributed to environmental exposures and genetic factors.MethodsWe evaluated all of the dermal ridge patterns of 66 children who had been exposed to either the anticonvulsant phenytoin alone or phenytoin and phenobarbital. We determined the frequency of each pattern, concordance between the fingers on the left and right hands, sex differences and total ridge counts in the drug‐exposed children and compared them to the findings in 716 unexposed comparison children. The frequency of each pattern was established in comparison to the most common type of pattern (ulnar loop), which showed that there were alterations in the frequency of arches, radial loops and whorls on specific fingers.ResultsEight (12.1%) of 66 children had three or more arch patterns, with all but one having been exposed to phenytoin and phenobarbital. Only one of these eight children was considered by the masked examiner to have fingernail hypoplasia. There was no evidence of asymmetry in the anticonvulsant‐exposed children. There were minor differences in the distribution of total ridge count.ConclusionsSubtle differences in several dermal ridge patterns, not just arch patterns, were present in anticonvulsant‐exposed children, primarily in those exposed to polytherapy: phenytoin and phenobarbital. Teratology 66:19–23, 2002. © 2002 Wiley‐Liss, Inc.
Modelling utility‐scale wind power plants. Part 2: Capacity credit
Authors: Milligan Michael R. 
Published: August 2002

AbstractAs the worldwide use of wind turbine generators in utility‐scale applications continues to increase, it will become increasingly important to assess the economic and reliability impact of these intermittent resources. Although the utility industry appears to be moving towards a restructured environment, basic economic and reliability issues will continue to be relevant to companies involved with electricity generation. This article is the second in a two‐part series that addresses modelling approaches and results that were obtained in several case studies and research projects at the National Renewable Energy Laboratory (NREL). This second article focuses on wind plant capacity credit as measured with power system reliability indices. Reliability‐based methods of measuring capacity credit are compared with wind plant capacity factor. The relationship between capacity credit and accurate wind forecasting is also explored. Published in 2000 by John Wiley & Sons, Ltd.