bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate carcinoma cells that have resided in bone have an upregulated IGF‐I axis
Authors: Rubin J. , Chung L.W.K. , Fan X. , Zhu L. , Murphy T.C. , Nanes M.S. , Rosen C.J. 
Published: December 2003

AbstractBACKGROUNDProstate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF‐I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF‐I in conjunction with endogenous IGF‐I contributes to the osteoblastic phenotype characteristic of metastatic PC.METHODSTo test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines.RESULTSUsing RIA, we found serum‐free conditioned media (CM) of LNCaP and C4‐2 had no measurable IGF‐I, whereas IGF‐I was easily detected in CM from C4‐2B cells at 24 hr (i.e., 1.8 ± 0.53 ng/mg cell protein). Real‐time PCR of IGF‐I mRNA showed that C4‐2B expressed 100‐fold more IGF‐I mRNA than LNCaP cells. In addition, C4‐2B expression of IGF‐I mRNA was substantially increased in the presence of exogenous IGF‐I to nearly twofold. While IGFBP‐3 and IGFBP‐1 were not detectable in the CM of any PC line, all cells secreted IGFBP‐2. C4‐2B cells produced 40% more IGFBP‐2 than LNCaP or C4‐2 cells (C4‐2B at 167 ± 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4‐2 and C4‐2B and at least equivalent protein expression.CONCLUSIONSOur results suggest that PC cells that have metastasized to bone have an upregulated IGF‐I regulatory system. This suggests an activated IGF‐I axis contributes to the host–PC interaction in promoting osteoblastic metastases. © 2003 Wiley‐Liss, Inc.
Application of the StrOligo algorithm for the automated structure assignment of complex N‐linked glycans from glycoproteins using tandem mass spectrometry
Authors: Ethier Martin , Saba Julian A. , Spearman Maureen , Krokhin Oleg , Butler Michael , Ens Werner , Standing Kenneth G. , Perreault Hélène 
Published: December 2003

AbstractOligosaccharides associated with proteins are known to give these molecules specific conformations and functions. Analysis of proteins would not be complete without studying the glycans. However, high‐throughput techniques in proteomics will soon overwhelm the current capacity of methods if no automation is incorporated into glycomics. New capabilities of the StrOligo algorithm introduced for this purpose (Ethier et al., Rapid Commun. Mass Spectrom., 2002; 16: 1743) will be discussed here. Experimental tandem mass spectra were acquired to test the algorithm using a hybrid quadrupole‐time‐of‐flight (QqTOF) instrument with a matrix‐assisted laser desorption/ionization (MALDI) source. The samples were N‐linked oligosaccharides from monoclonal antibody IgG, beta interferon and fetuin, detached by enzymatic deglycosylation and labeled at the reducing end. Improvements to the program were made in order to reduce the need for user intervention. StrOligo strips the spectra down to monoisotopic peaks only. The algorithm first builds a relationship tree, accounting for each observed loss of a monosaccharide moiety, and then analyzes the tree and proposes possible structures from combinations of adducts and fragment ion types. A score, which reflects agreement with experimental results, is then given to each proposed structure. The program then decides which combination is the best one and labels relevant peaks in the experimental mass spectrum using a modified nomenclature. The usefulness of the algorithm has been demonstrated by assigning structures to several glycans released from glycoproteins. The analysis was completed in less than 2 minutes for any glycan, which is a substantial improvement over manual interpretation. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of atrazine, deethylatrazine and simazine in water at parts‐per‐trillion levels using solid‐phase extraction and gas chromatography/ion trap mass spectrometry
Authors: Ma W. T. , Cai Zongwei , Jiang G. B. 
Published: December 2003

AbstractMethods for trace analysis of atrazine and simazine in water have been developed by using stable‐isotope dilution with detection by gas chromatography/mass spectrometry. D5‐Atrazine was used as the internal standard for the determination of atrazine and deethylatrazine, while 13C3‐simazine was used for simazine analysis. Water samples were fortified with known amounts of the internal standards and submitted to solid‐phase extraction with a C18 bonded‐silica cartridge. A gas chromatograph coupled with an ion‐trap mass spectrometer was used to analyze the water sample extracts. Method detection limits were 38 parts‐per‐trillion (ppt) for atrazine and deethylatrazine and 75 ppt for simazine. The accuracy of the method, represented by relative analytical errors, was less than 15%, and the method precision was less than 5% (relative standard deviation, n = 9). The method was successfully applied to analyze surface water samples collected from a reservoir and a river at ppt levels. Copyright © 2003 John Wiley & Sons, Ltd.
Ionization enhancement in atmospheric pressure chemical ionization and suppression in electrospray ionization between target drugs and stable‐isotope‐labeled internal standards in quantitative liquid chromatography/tandem mass spectrometry
Authors: Liang H. R. , Foltz R. L. , Meng M. , Bennett P. 
Published: December 2003

AbstractThe phenomena of ionization suppression in electrospray ionization (ESI) and enhancement in atmospheric pressure chemical ionization (APCI) were investigated in selected‐ion monitoring and selected‐reaction monitoring modes for nine drugs and their corresponding stable‐isotope‐labeled internal standards (IS). The results showed that all investigated target drugs and their co‐eluting isotope‐labeled IS suppress each other's ionization responses in ESI. The factors affecting the extent of suppression in ESI were investigated, including structures and concentrations of drugs, matrix effects, and flow rate. In contrast to the ESI results, APCI caused seven of the nine investigated target drugs and their co‐eluting isotope‐labeled IS to enhance each other's ionization responses. The mutual ionization suppression or enhancement between drugs and their isotope‐labeled IS could possibly influence assay sensitivity, reproducibility, accuracy and linearity in quantitative liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, calibration curves were linear if an appropriate IS concentration was selected for a desired calibration range to keep the response factors constant. Copyright © 2003 John Wiley & Sons, Ltd.
Sialylation analysis of O‐glycosylated sialylated peptides from urine of patients suffering from Schindler's disease by Fourier transform ion cyclotron resonance mass spectrometry and sustained off‐resonance irradiation collision‐induced dissociation
Authors: Froesch Martin , Bindila Laura , Zamfir Alina , Peter‐Katalinić Jasna 
Published: December 2003

AbstractA strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS) for screening of complex glycoconjugate mixtures containing O‐linked glycopeptides and O‐glycosylated amino acids with α‐N‐acetylgalactosaminyl residues is presented. To detect and identify O‐glycoforms present in urine of patients suffering from hereditary N‐acetylhexosaminidase deficiency (known as Schindler's disease), present at 100 times higher concentrations than in urine of healthy controls, new accurate methods for mapping and sequencing were required. In the mass spectrometric analysis particular attention has to be paid to original sialylation patterns, because of the potential lability of the sialic acid moiety during the desorption/ionization process. Negative ion nanoelectrospray ionization (nanoESI) FTICR‐MS at 9.4 T is shown here to represent a method of choice for identification of single components in such complex glycomixtures due to high resolution and mass accuracy. By optimization of sustained off‐resonance irradiation collision‐induced dissociation tandem mass spectrometry (SORI‐CID‐MS2) in the negative ion mode, the type and sequence of the sialylated glycopeptide components were determined from their fragmentation patterns. Additionally, implementation of SORI‐CID‐MS3 provides detailed information for sialylation analysis. The potential diagnostic value of this approach is discussed. Copyright © 2003 John Wiley & Sons, Ltd.
On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles
Authors: Kendziorski C. M. , Newton M. A. , Lan H. , Gould M. N. 
Published: December 2003

AbstractDNA microarrays provide for unprecedented large‐scale views of gene expression and, as a result, have emerged as a fundamental measurement tool in the study of diverse biological systems. Statistical questions abound, but many traditional data analytic approaches do not apply, in large part because thousands of individual genes are measured with relatively little replication. Empirical Bayes methods provide a natural approach to microarray data analysis because they can significantly reduce the dimensionality of an inference problem while compensating for relatively few replicates by using information across the array. We propose a general empirical Bayes modelling approach which allows for replicate expression profiles in multiple conditions. The hierarchical mixture model accounts for differences among genes in their average expression levels, differential expression for a given gene among cell types, and measurement fluctuations. Two distinct parameterizations are considered: a model based on Gamma distributed measurements and one based on log‐normally distributed measurements. False discovery rate and related operating characteristics of the methodology are assessed in a simulation study. We also show how the posterior odds of differential expression in one version of the model is related to the ratio of the arithmetic mean to the geometric mean of the two sample means. The methodology is used in a study of mammary cancer in the rat, where four distinct patterns of expression are possible. Copyright © 2003 John Wiley & Sons, Ltd.
Non‐parametric bootstrap confidence intervals for the intraclass correlation coefficient
Authors: Ukoumunne Obioha C. , Davison Anthony C. , Gulliford Martin C. , Chinn Susan 
Published: December 2003

AbstractThe intraclass correlation coefficient ρplays a key role in the design of cluster randomized trials. Estimates of ρ obtained from previous cluster trials and used to inform sample size calculation in planned trials may be imprecise due to the typically small numbers of clusters in such studies. It may be useful to quantify this imprecision. This study used simulation to compare different methods for assigning bootstrap confidence intervals to ρfor continuous outcomes from a balanced design. Data were simulated for combinations of numbers of clusters (10, 30, 50), intraclass correlation coefficients (0.001, 0.01, 0.05, 0.3) and outcome distributions (normal, non‐normal continuous). The basic, bootstrap‐t, percentile, bias corrected and bias corrected accelerated bootstrap intervals were compared with new methods using the basic and bootstrap‐t intervals applied to a variance stabilizing transformation of ρ. The standard bootstrap methods provided coverage levels for 95 per cent intervals that were markedly lower than the nominal level for data sets with only 10 clusters, and only provided close to 95 per cent coverage when there were 50 clusters. Application of the bootstrap‐t method to the variance stabilizing transformation of ρimproved upon the performance of the standard bootstrap methods, providing close to nominal coverage. Copyright © 2003 John Wiley & Sons, Ltd.
Estimating the incidence of subclinical infections withLegionella Pneumoniausing data augmentation: analysis of an outbreak in The Netherlands
Authors: Nagelkerke Nico J. D. , Boshuizen Hendriek C. , de Melker Hester E. , Schellekens Joop F. P. , Peeters Marcel F. , Spaendonck Marina Conyn‐van 
Published: December 2003

AbstractInfections withLegionellabacteria can cause a potentially lethal form of pneumonia known as legionnaires' disease. In 1999 a major outbreak, causing 31 deaths, occurred among visitors and exhibitors of a consumer fair in The Netherlands. The epidemiology of subclinical infections is largely unknown, as there is no reliable method to diagnose such infections. To explore the incidence of subclinical infections, IgG and IgM antibody levels among exhibitors were compared to those among a representative sample of the Dutch population. As exhibitors were assumed to comprise both infected and uninfected individuals, their antibody levels were modelled as a mixture distribution. As infected individuals are expected to cluster around a point source, the spatial aspect of the spread of infections was taken into account. To estimate the distribution of antibody levels among infected individuals and to impute infection status among exhibitors, data augmentation was used. Subclinical infection appeared to be very common and its frequency declined with the distance from the putative source of the outbreak. Copyright © 2003 John Wiley & Sons, Ltd.
Power comparison of two‐sided exact tests for association in 2 × 2 contingency tables using standard, mid p and randomized test versions
Authors: Lydersen Stian , Laake Petter 
Published: December 2003

AbstractExact Pearson's chi square, likelihood ratio (LR), and Fisher's tests are obtained from the conditional distribution of its test statistic, given therow and column sums of the contingency table. The power and obtained significance level of the standard, mid p, and randomized versions of these tests are compared for two‐sided tests in 2 × 2 tables, using binomial and multinomial sampling. The mid p type I error probabilities seldom exceed thenominal significance level. The mid p and randomized test versions have approximately the same power, and higher power than the standard test version. The power of the Pearson's chi square, LR and Fisher's test differ, and they differ in approximately the same way for standard, mid p and randomized test versions for any given set of parameters. There is no general ranking between the three tests. In many cases, Pearson's chi square and Fisher's tests have almost equal power, and higher power than LR. In a few cases, perhaps characterized by poorly balanced designs, LR performs best. Fisher's test seems to be slightly more robust even if the design is poor. Copyright © 2003 John Wiley & Sons, Ltd.
Sample size re‐estimation in group‐sequential response‐adaptive clinical trials
Authors: C. Morgan Caroline 
Published: December 2003

AbstractIn clinical trials where the variances of the response variables are unknown, in accurate estimates of these can affect the type II error rate considerably. More accurate estimates of the variances may be obtained by taking a look at the data available part way through the trial and re‐calculating the required sample size based on these new estimates. The main impetus for sample size re‐estimation came from a two‐stage procedure developed by Stein in 1945 and the literature is now replete with variations on this approach. In this paper, existing sample size re‐estimation methods for both fixed sample and sequential clinical trial models will be reviewed. These will then be extended for use in group‐sequential response‐adaptive designs. In particular, a test for a recently developed group‐sequential response‐adaptive design, which compares two treatments with immediate normally distributed responses and unknown variances, is presented based on a modified version of Stein's test. The principal modifications involve updating the required sample size at each interim analysis and calculating thetest statistic based on the current estimates of the variances. Hence, all the available information is used at each stage. Simulation is used to assess to what extent the updating of the required sample size at each interim analysis in the new test helps to attain the nominal error rates. The test is compared to modified versions of a simple test and a Stein‐type group sequential t‐test studied in the recent literature. These tests calculate the required sample sizes based on less accurate estimates of the variances. The type I error rate is close to the nominal value and the power is more accurately maintained in the new test. Copyright © 2003 John Wiley & Sons, Ltd.
Intervention effects in observational survival studies with an application in total hip replacements
Authors: Friede Tim , Henderson Robin 
Published: December 2003

AbstractTime to revision is a common and clinically relevant endpoint for studies of patients with total hip replacement. Because failures occur rarely within the first years after replacement, new surgical techniques and materials are often implemented without evidence of their effectiveness from randomized trials. Observational data may be available but this relies on the use of historical controls which has been heavily criticized. Instead the use of change‐point methods has been suggested to detect changes caused by successfully implemented interventions. In the setting of a proportional hazards model we develop a semi‐parametric changepoint method to detect changes in baseline hazard. The procedure is motivated by and applied to a clinical study in patients with total hip replacements, where the effect of a new cement type is of interest. Power properties of the proposed method are investigated. Copyright © 2003 John Wiley & Sons, Ltd.
Editorial
Authors: Cooke John , Denvir Tim 
Published: December 2003

Abstract.
In June 1999, the first International Workshop on Integrated Formal Methods was held at York University in the UK. The primary aim of the workshop was the combination of behavioural and state-based formalisms to yield practical solutions to industrial problems.
The workshop proceedings were edited by Keijiro Araki, Andy Galloway and Kenji Taguchi and are available as “IFM99” (ISBN 1-85233-107-0, published by Springer). After the workshop, selected authors were invited to develop journal versions of their papers, incorporating further extensions, corrections and revisions. This was arranged by Andy Galloway who then passed the papers to the journal for refereeing. And here we must record our sincere thanks to Andy. Without his efforts this issue of the journal would simply not have been possible.
Following reports from referees and senior colleagues from the editorial board (and the withdrawal of one submission for publication in a book) five papers were accepted for publication here. We hope that those rejected will be further revised and resubmitted; they contained good work but required further development.
The common theme is, predictably, the marrying of component specification with control of the interconnecting system, and the first 4 papers all present variations on the theme of Z + CSP. Sühl adds an additional structuring mechanism to Z and CSP and targets his application area as real-time embedded systems, whereas Derrick and Boiten use Object-Z to give partial specifications (viewpoints) which are then combined using CSP. Smith and Hayes describe Real-time Object-Z, which results from the integration of Object-Z with timed traces, and Mahony and Dong investigate the necessary formal underpinning required to combine Timed CSP and Object-Z by means of a trace model.
The final paper, by Große-Rhode, introduces and illustrates a mechanism for checking the compatibility of different partial specifications and for coping with composite specifications in which different formalisms have been used.
Whether or not this area of formal methods research merely allows us to integrate different, more ‘appropriate’, specification languages or gives rise to new hybrid languages remains to be seen. What is certain is that there are still many problems to be tackled and technology to be transferred.
An Overview of the Integrated Formalism RT-Z
Authors: Sühl Carsten 
Published: December 2003

Abstract.
We present an integration of the formal specification languages Z and timed CSP, called RT-Z, incorporating their combined strengths in a coherent frame. To cope with complex systems, RT-Z is equipped with structuring constructs built on top of the integration, because both Z and timed CSP lack appropriate facilities. The formal semantics of RT-Z, based on the denotational semantics of Z and timed CSP, is a prerequisite for preciseness and mathematical rigour. RT-Z is intended to be used in the requirements definition and design phases of the system and software development process. The envisaged application area is the development of real-time embedded systems.
POP, A Broad-Spectrum Programming Language, 1967–2002
Authors: Popplestone Robin 
Published: December 2003

Abstract.
This paper discusses the POP-2 language and Multipop time-sharing system developed during the second half of the 1960s. POP-2's expressiveness spanned numeric and symbolic programming and supported experiments in logic of programming languages (by Boyer and Moore) and programming language concepts (for example, Michie's memoisation). The paper also discusses how the goals of POP-2 might be achieved in a successor language.
Shallow Linear Action Graphs and their Embeddings
Authors: Leifer James J. , Milner Robin 
Published: December 2003

Abstract.Action calculi, which generalise process calculi such as Petri nets, π-calculusand ambient calculus, have been presented in terms ofaction graphs. We here offerlinearaction graphs as a primitive basis for action calculi. This paper presents the category of embeddings of undirected linear action graphs without nesting, using a novel form of graphical reasoning which simplifies some otherwise complex manipulations in regular algebra. The results are adapted in a few lines to directed graphs. This work is part of a long-term search for a uniform behavioural theory for process calculi.
Testing Conditions for Communicating Stream X-machine Systems
Authors: Ipate Florentin , Holcombe Mike 
Published: December 2003

Abstract.

X-machines were proposed by Holcombe as a possible specification language and since then a number of further investigations have demonstrated that the model is intuitive and easy to use. In particular,
stream X-machines
(
SXM
), a particular class of X-machines, have been found to be extremely useful in practice. Furthermore, a method of testing systems specified as SXMs exists and is proved to detect all faults of the implementation provided that the system meets certain
“design for test conditions”
. Recently, a
system of communicating SXMs
was introduced as a means of modelling parallel processing. This paper proves that each communicating machine component can be transformed in a straightforward manner so that the entire system will behave like a single stream X-machine - the equivalent SXM of the system. The paper goes on to investigate the applicability of the SXM testing method to a system of communicating SXMs and identifies a class of communicating SXMs for which the equivalent SXM of the system meets the “design for test conditions”.