bluuebunny/crossref_metadata_2025 huggingface dataset:
Exhaustive evolving factor analysis (E‐EFA)
Authors: Whitson Andrew C. , Maeder Marcel
Published: September 2002

Reliable information about concentration windows is crucial for many self‐modeling curve resolution (SMCR) methods. Algorithms based on evolving factor analysis (EFA)‐type methods enable the detection of the beginnings and endings of concentration profiles. Often this is sufficient to define concentration windows. However, under certain circumstances the connection of beginnings and endings is ambiguous, and wrong connection results in erroneous analysis. Systematic rank analysis of all possible submatrices of a matrix of data can result in unambiguous identification of the correct connectivity of beginnings and endings of concentration profiles. Steps are proposed which accelerate the calculations dramatically. Copyright © 2001 John Wiley & Sons, Ltd.
Calculation of maximum and minimum band boundaries of feasible solutions for species profiles obtained by multivariate curve resolution
Authors: Tauler R.
Published: September 2002

A method for the calculation of maximum and minimum band boundaries of feasible solutions corresponding to the species profiles estimated by multivariate curve resolution is presented. The method is based on a non‐linear constrained optimization of an objective function defined by the ratio of the signal contribution of a particular species to the whole measured signal. Implementation of constraints such as normalization, closure, non‐negativity, unimodality and local rank/selectivity during the non‐linear optimization and their effect on the calculation of the feasible solutions are studied in detail. Calculation of the band boundaries is shown for different simulated and real two‐way data examples of increasing complexity. Copyright © 2001 John Wiley & Sons, Ltd.
Wavelet hybrid direct standardization of near‐infrared multivariate calibrations
Authors: Tan Hu‐Wei , Brown Steven D.
Published: September 2002

A novel standardization method called wavelet hybrid direct standardization (WHDS) is proposed. It is based on a new wavelet reconstruction algorithm in which approximation and detail spectra are reconstructed separately. Piecewise direct standardization (PDS) and direct standardization (DS) are used to correct the differences of original spectra by transforming the reconstructed approximation and detail spectra respectively. The proposed method is applied to near‐infrared data and its performance is compared with current methods. Result shows that, using the wavelet multi‐resolution technique and combining PDS and DS, the WHDS algorithm allows a more robust and reliable means for standardization when transfer standards are available. Copyright © 2001 John Wiley & Sons, Ltd.
An index formalism that generalizes the capabilities of matrix notation and algebra to n‐way arrays
Authors: Harshman Richard A.
Published: September 2002

The capabilities of matrix notation and algebra are generalized to n‐way arrays. The resulting language seems easy to use; all the capabilities of matrix notation are retained and most carry over naturally to the n‐way context. For example, one can multiply a three‐way array times a four‐way array to obtain a three‐way product. Many of the language's key characteristics are based on the rules of tensor notation and algebra. The most important example of this is probably the incorporation of subscript/index‐related information into both the names of array objects and the rules used to operate on them. Some topics that emerge are relatively unexplored, such as inverses of n‐way arrays; these might prove interesting for future theoretical study. Copyright © 2001 John Wiley & Sons, Ltd.
Statistical analysis of catalyst degradation in a semi‐continuous chemical production process
Authors: Kaskavelis Eleftherios , Martin Elaine , Jonathan Philip , Morris Julian
Published: September 2002

The effect of decaying catalyst efficacy in a commercial‐scale, semi‐continuous petrochemical process was investigated. The objective was to gain a better understanding of process behaviour and its effect on production rate. The process includes a three‐stage reaction performed in fixed bed reactors. Each of the three reaction stages consists of a number of catalyst beds that are changed periodically to regenerate the catalyst. Product separation and reactant recycling are then performed in a series of distillation columns. In the absence of specific measurements of the catalyst properties, process operational data are used to assess catalyst decay. A number of statistical techniques were used to model production rate as a function of process operation, including information on short‐ and long‐term catalyst decay. It was found that ridge regression, partial least squares and stepwise selection multiple linear regression yielded similar predictive models. No additional benefit was found from the application of non‐linear partial least squares or Curds and Whey. Finally, through time series profiles of total daily production volume, corresponding to individual in‐service cycles of the different reaction stages, short‐term catalyst degradation was assessed. It was shown that by successively modelling the process as a sequence of batches corresponding to cycles of each reaction stage, considerable economic benefit could be realized by reducing the maximum cycle length in the third reaction stage. Copyright © 2001 John Wiley & Sons, Ltd.
On unifying multiblock analysis with application to decentralized process monitoring
Authors: Qin S. Joe , Valle Sergio , Piovoso Michael J.
Published: September 2002

Westerhuis et al. (J. Chemometrics 1998; 12: 301–321) show that the scores of consensus PCA and multiblock PLS (Westerhuis and Coenegracht, J. Chemometrics 1997; 11: 379–392) can be calculated directly from the regular PCA and PLS scores respectively. In this paper we show that both the loadings and scores of consensus PCA can be calculated directly from those of regular PCA, and the multiblock PLS loadings, weights and scores can be calculated directly from those of regular PLS. The orthogonal properties of four multiblock PCA and PLS algorithms are explored. The use of multiblock PCA and PLS for decentralized monitoring and diagnosis is derived in terms of regular PCA and PLS scores and residuals. While the multiblock analysis algorithms are basically equivalent to regular PCA and PLS, blocking of process variables in a large‐scale plant based on process knowledge helps to localize the root cause of the fault in a decentralized manner. New definitions of block and variable contributions to SPE and T 2 are proposed for decentralized monitoring. This decentralized monitoring method based on proper variable blocking is successfully applied to an industrial polyester film process. Copyright © 2001 John Wiley & Sons, Ltd.
Weighing schemes in multivariate data analysis
Authors: Höskuldsson Agnar
Published: September 2002

A collection of methods will be presented, designed to reflect special purpose or features in data. Many chemometric methods can be viewed as an application of special weighing schemes of the type presented here. After a short review of the H‐principle of mathematical modelling, it will be applied to develop different weighing schemes and some simple ways to judge the quality or significance of a weighing scheme. Weighing schemes for two‐way data will be established. We shall show how a loading vector can be adapted to a given score vector in order to improve the possibilities of interpretation of the results. These results will be extended to multiway data. It will be shown how we can develop different weighing schemes for multiway data depending on the purpose or interpretability of the results. The importance of these weighing schemes is due to the fact that they yield or emphasize the part of data that is ‘in focus’ in relation to the task in question. Copyright © 2001 John Wiley & Sons, Ltd.
Rapid estimation of chemical kinetics by implicit calibration. I
Authors: Taavitsainen Veli‐Matti , Haario Heikki
Published: September 2002

In this study, methods for estimating kinetic parameters from on‐line measurements of batch reactions are developed. The basic idea is to combine non‐linear parameter estimation with implicit calibration between measured spectra and concentrations given by a known kinetic model. Several alternatives for the calibration step are discussed and the three most promising methods have been studied more closely. The basic ideas and identifiability questions are elucidated by simulation studies with simple kinetic models. The simulations show that the implicit calibration method works also with uncalibrated chromatograms. Two real esterification reactions with spectroscopic data are studied. In the first one, concentration data are available and our method gives results quite similar to those obtained in more traditional ways. The latter reaction, however, was a fast one and consequently off‐line calibration based on known mixtures failed. In contrast, our method gave almost identical parameter values to the ones obtained by an independent study on the same reaction based on a complicated on‐line chromatographic measurement system. In this case the results were compared with a new way of using pure component spectra and generalized ridge regression with stoichiometric constraints. Our studies show that the most important factors in obtaining reliable results are proper design of the batch experiments, proper weighting of the initial measurements of each batch and proper measure for goodness of fit. Copyright © 2001 John Wiley & Sons, Ltd.
Understanding the collinearity problem in regression and discriminant analysis
Authors: Næs Tormod , Mevik Bjørn‐Helge
Published: September 2002

This paper presents a discussion of the collinearity problem in regression and discriminant analysis. The paper describes reasons why the collinearity is a problem for the prediction ability and classification ability of the classical methods. The discussion is based on established formulae for prediction errors. Special emphasis is put on differences and similarities between regression and classification. Some typical ways of handling the collinearity problems based on PCA will be described. The theoretical discussion will be accompanied by empirical illustrations. Copyright © 2001 John Wiley & Sons, Ltd.
Hierarchical principal component analysis (PCA) and projection to latent structure (PLS) technique on spectroscopic data as a data pretreatment for calibration
Authors: Janné K. , Pettersen J. , Lindberg N.‐O. , Lundstedt T.
Published: September 2002

Spectroscopic data consists of several hundred to some thousand variables, wherein most of the variables are autocorrelated. When PCA and PLS techniques are used for the interpretation of these kinds of data, the loading plots are usually complex due to the covariation in the spectrum, and therefore difficult to correlate to the corresponding score plot. One of the standard methods used to decrease the influence of light scatter or shifts of the spectra is the multiplicative scatter correction technique. Another technique is the hierarchical multiblock segmentation technique, where new variables are created from the original data by blocking the spectra into sub spectra, and then projecting the sub spectra by PCA. These new variables are then used in the coming PCA or PLS calculations. These techniques reduce the random and non‐wanted signals from e.g. light scatter, but still conserve all systematic information in the signals, but the greatest advantage is that the technique gives an easier interpretation of the correlation between scores and the loadings. Two examples are presented; the attenuated total reflection (ATR) and NIR, which show the advantages as well as the implementation of the method. Copyright © 2001 John Wiley & Sons, Ltd.
Multivariate process monitoring of a newsprint mill. Application to modelling and predicting COD load resulting from de‐inking of recycled paper
Authors: Eriksson Lennart , Hagberg Peggy , Johansson Erik , Rännar Stefan , Whelehan Oliver , Åström Anders , Lindgren Torbjörn
Published: September 2002

Multivariate process monitoring was applied to understand the influence of numerous production parameters on the release of organic matter into the effluent of a newsprint mill. The release was characterized by measuring the chemical oxygen demand (COD). The relationships between over 50 process variables and the COD load were investigated using PLS regression and time series analysis. The results showed that variations in COD could be predicted accurately. Furthermore, model interpretation identified the most influential process parameters. Copyright © 2001 John Wiley & Sons, Ltd.
The GIFI approach to non‐linear PLS modeling
Authors: Berglund Anders , Kettaneh Nouna , Uppgård Lise‐Lott , Wold Svante , Bendwell Nancy , Cameron Dave R.
Published: September 2002

The GIFI approach to non‐linear modeling involves the transformation of quantitative variables to a set of 1/0 dummies in a similar manner to the way qualitative variables are coded. This is followed by analyzing the sets of 1/0 dummies by principal component analysis, multiple regression or, as discussed here, PLS. The patterns of the resulting coefficients indicate the nature of the non‐linearities in the data. Here the potential uses and limitations of PLS regression, in combination with four variants of GIFI coding, are investigated using both simulated and empirical data sets. Copyright © 2001 John Wiley & Sons, Ltd.
Interpretation of regression coefficients under a latent variable regression model
Authors: Burnham Alison J. , MacGregor John F. , Viveros Roman
Published: September 2002

In standard linear regression where the predictor matrix X is of full rank, the regression coefficients are clearly defined as the parameters B appearing in the linear regression model. In latent variable models there is no direct relationship between the predictor variables and response variables. Rather they are both related to an underlying reduced‐rank set of latent variables. Recent papers have proposed different methods for obtaining approximate covariance matrices for the estimates of the regression coefficients from methods such as partial least squares (PLS) and for using them to determine ‘confidence intervals’, for variable selection and for judging variable importance. However, in the latent variable model a matrix of regression coefficients, B, does not even appear as a parameter matrix. In the situation where the data follow such a model, it is therefore uncertain how the regression coefficients and, by extension, any covariance matrices and ‘confidence intervals’ should be interpreted. In this paper we show that any inference is critically dependent upon how one defines these regression coefficients. Two definitions for the regression coefficients are given that are consistent with the latent variable model. Which of these definitions is more relevant is shown to be highly dependent on the goals of the analysis. Therefore one must be clear on the definition one is using for these coefficients when building predictive models, when screening variables based on them or when using them to make interpretations about the system. Under standard normality assumptions, different estimation methods such as ordinary least squares (OLS) and PLS are shown to provide very different distributions for the regression coefficient estimates when the data follow a latent variable model. This is shown to be not just a matter of the PLS coefficients being biased or the OLS estimates having large variance, but of more complex differences implied by the structure of the model parameters in the latent variable model. How the distributions for these estimates relate to the definitions given in this paper is explored here. It is shown for a simple case that the relative size of the PLS estimates, on average, tends to reflect the latent variable loadings, whereas the relative size of the OLS estimates, on average, is a function not only of the loadings but also of the error variances for the predictor variables. Thus in this particular case it appears that the relative size of the B parameters from PLS reflects the underlying latent structure, whereas those from OLS also reflect the error structure of the predictor variables. Copyright © 2001 John Wiley & Sons, Ltd.
2D wavelet analysis and compression of on‐line industrial process data
Authors: Trygg Johan , Kettaneh‐Wold Nouna , Wallbäcks Lars
Published: September 2002

In recent years the wavelet transform (WT) has interested a large number of scientists from many different fields. Pattern recognition, signal processing, signal compression, process monitoring and control, and image analysis are some areas where wavelets have shown promising results. In this paper, 2D wavelet analysis and compression of near‐infrared spectra for on‐line monitoring of wood chips is reviewed. We introduce a new parameter for outlier detection, distance to model in wavelet space (DModW), which is analogous to the residual parameter (DModX) used in principal component analysis (PCA) and partial least squares analysis (PLS). Additionally, we describe the wavelet power spectrum (WPS), the wavelet analogue of the power spectrum. The WPS gives an overview of the time–frequency content in a signal. In the example given, wavelets improved the detection of spectral shift and compressed data 1000‐fold without degrading the quality of the 2D wavelet‐compressed PCA model. The example concerned an industrial process‐monitoring situation where near‐infrared spectra are measured on‐line on top of a conveyer belt filled with wood chips at a Swedish pulp plant. Copyright © 2001 John Wiley & Sons, Ltd.
Feasibility of EMF‐induced pipeline wall friction reduction by PLS2 intercalibration of acoustic chemometrics and reference laser velocimetry
Authors: Esbensen Kim H. , Waskaas Magne , Matveyev Inger Hedvig , Wolden Kjell Erik , Lode Jan Gunnar , Lied Thorbjørn T. , Halstensen Maths
Published: September 2002

Various applied physics lines of research on the interactions between electromagnetics and flowing water have led to the suggestion that it might be possible to reduce pipeline wall friction by applying a transverse electromagnetic field (EMF). We here conduct a feasibility study of the shape and magnitude of internal fluid flow velocity profiles of hydropower turbine inlet pipelines, with and without an EMF. The flow velocity profile itself can only be measured in transparent pipeline sections with the aid of refined laser velocimetric equipment, which can never be employed in realistic hydropower settings however. The objective of the present studies is therefore to use a much simpler alternative, i.e. an acoustic chemometric approach, relying on ‘clamp‐on’ acoustic sensors applied directly to the outer wall of the pipeline. Our results show that it is fully possible to verify the ‘on/off’ status of the applied EMF using either of the alternative modalities, laser velocimetry and acoustic chemometrics, i.e. to verify an increased water flux when the EMF is ‘on’. The interactions between this feature and realistic changing temperatures (15–27  °C) as well as varying overall water velocities (1–4 m s−1) are explored. It is concluded that the temperature sensitivities of both modalities can be compensated for and, furthermore, that the temperature‐compensated modelling is velocity‐invariant. This opens up an interesting avenue for field on‐line EMF‐induced wall friction reduction monitoring and control. Our final feasibility demonstration concerns direct PLS2 intercalibration of the acoustic chemometric monitoring data (X) with the laser velocimetric reference profiles (Y). This translates into a new acoustic chemometric possibility for ‘seeing’ the effects of the EMF‐modified velocity profiles directly from the suitably calibrated acoustic signals alone. We find that a 42‐Y‐variable PLS2 model can be validated as X, Y: 30%, 70% respectively, fully satisfactory for prediction purposes of the velocity in an outer (near‐wall) 5–6 mm annular flow regimen. With this we have positive proof that acoustic chemometric monitoring can be used for predicting the effects of the EMF. Upscaling to field‐scale pipelines remains. Copyright © 2001 John Wiley & Sons, Ltd.
The price paid for the second‐order advantage when using the generalized rank annihilation method (GRAM)
Authors: Faber Nicolaas (Klaas) M.
Published: September 2002

In a ground‐breaking paper, Linder and Sundberg developed a statistical framework for the calibration of bilinear data (Chemometrics Intell. Lab. Syst. 1998; 42: 159–178). Within this framework they formulated three different predictor construction methods (J. Chemometrics accepted), namely a so‐called naive method, a least squares (LS) method and a refined version of the latter that takes account of the calibration uncertainty. They showed that the naive method is statistically less efficient than the others under the assumption of white noise. In the current work a close relationship is established between the generalized rank annihilation method (GRAM) and the naive method by comparing expressions for prediction variance. The main conclusion is that the relatively poor efficiency of GRAM is the price one pays for obtaining the second‐order advantage with a single calibration sample. Copyright © 2001 John Wiley & Sons, Ltd.
Application of PARAFAC2 to fault detection and diagnosis in semiconductor etch
Authors: Wise Barry M. , Gallagher Neal B. , Martin Elaine B.
Published: September 2002

Monitoring and fault detection of batch chemical processes are complicated by stretching of the time axis, resulting in batches of different length. This paper offers an approach to the unequal time axis problem using the parallel factor analysis 2 (PARAFAC2) model. Unlike PARAFAC, the PARAFAC2 model does not assume parallel proportional profiles, but only that the matrix of profiles preserves its ‘inner product structure’ from sample to sample. PARAFAC2 also allows each matrix in the multiway array to have a different number of rows. It has previously been demonstrated how the PARAFAC2 model can be used to model chromatographic data with retention time shifts. Fault detection and, to a lesser extent, diagnosis in a semiconductor etch process are considered in this paper. It is demonstrated that PARAFAC2 can effectively model batch process data from semiconductor manufacture with unequal dimension in one of the orders, such as the unequal batch length problem. It is shown that the PARAFAC2 model has approximately the same sensitivity to faults as other competing methods, including principal component analysis (PCA), unfold PCA (often referred to as multiway PCA), trilinear decomposition (TLD) and conventional PARAFAC. The advantage of PARAFAC2 is that it is easier to apply than MPCA, TLD and PARAFAC, because unequal batch lengths can be handled directly rather than through preprocessing methods. It also provides additional diagnostic information: the recovered batch profiles. It is likely, however, that it is less sensitive to faults than conventional PARAFAC. Copyright © 2001 John Wiley & Sons, Ltd.
Distribution of thyrotropin‐releasing hormone (TRH) immunoreactivity in the brain of the zebrafish (Danio rerio)
Authors: Díaz María Luz , Becerra Manuela , Manso María Jesús , Anadón Ramón
Published: September 2002

The distribution of thyrotropin‐releasing hormone (TRH) in the brain of the adult zebrafish was studied with immunohistochemical techniques. In the telencephalon, abundant TRH‐immunoreactive (TRHir) neurons were observed in the central, ventral, and supra‐ and postcommissural regions of the ventral telencephalic area. In the diencephalon, TRHir neurons were observed in the anterior parvocellular preoptic nucleus, the suprachiasmatic nucleus, the lateral hypothalamic nucleus, the rostral parts of the anterior tuberal nucleus and torus lateralis, and the posterior tuberal nucleus. Some TRHir neurons were also observed in the central posterior thalamic nucleus and in the habenula. The mesencephalon contained TRHir cells in the rostrodorsal tegmentum, the Edinger‐Westphal nucleus, the torus semicircularis, and the nucleus of the lateral lemniscus. Further TRHir neurons were observed in the interpeduncular nucleus. In the rhombencephalon, TRHir cells were observed in the nucleus isthmi and the locus coeruleus, rostrally, and in the vagal lobe and vagal motor nucleus, caudally. In the forebrain, TRHir fibers were abundant in several regions, including the medial and caudodorsal parts of the dorsal telencephalic area, the ventral and commissural parts of the ventral telencephalic area, the preoptic area, the posterior tubercle, the anterior tuberal nucleus, and the posterior hypothalamic lobe. The dorsal thalamus exhibited moderate TRHir innervation. In the mesencephalon, the optic tectum received a rich TRHir innervation between the periventricular gray zone and the stratum griseum centrale. A conspicuous TRHir longitudinal tract traversed the tegmentum and extended to the rhombencephalon. The medial and lateral mesencephalic reticular areas and the interpeduncular nucleus were richly innervated by TRHir fibers. In the rhombencephalon, the secondary gustatory nucleus received abundant TRHir fibers. TRHir fibers moderately innervated the ventrolateral and ventromedial reticular area and richly innervated the vagal lobe and Cajal's commissural nucleus. Some TRHir fibers coursed in the lateral funiculus of the spinal cord. Some TRHir amacrine cells were observed in the retina. The wide distribution of TRHir neurons and fibers observed in the zebrafish brain suggests that TRH plays different roles. These results in the adult zebrafish reveal a number of differences with respect to the TRHir systems reported in other adult teleosts but were similar to those found during late developmental stages of trout (Díaz et al., 2001). J. Comp. Neurol. 450:45–60, 2002. © 2002 Wiley‐Liss, Inc.
Effect of boundary element details on the seismic deformation capacity of structural walls
Authors: Oh Young‐Hun , Han Sang Whan , Lee Li‐Hyung
Published: September 2002

The objective of this study is to investigate the effect of boundary element details of structural walls on their deformation capacities. Structural walls considered in this study have different sectional shapes and/or transverse reinforcement content at the boundaries of the walls (called boundary element details hereafter). Four full‐scale wall specimens (3000mm (hw)×1500mm (lw)×200mm (T)) were fabricated and tested. Three specimens are rectangular in section and the other specimen has a barbell‐shaped cross‐section (a wall with boundary columns). The rectangular wall specimens are reinforced according to the common practice used for reinforced concrete residence buildings in Korea and Chile. In this study, the primary variable for these rectangular specimens is the content of transverse reinforcement to confine the boundary elements of a wall. The barbell‐shaped specimen was designed in compliance with ACI 318‐95. The response of the barbell‐shaped specimen is compared with those of other rectangular specimens. The effective aspect ratio of the specimens is set to two in this study. Based on the experimental results, it is found that the deformation capacities of walls, which are represented by displacement ductility, drift ratio and energy dissipation capacities, are affected by the boundary element details. Copyright © 2002 John Wiley & Sons, Ltd.
Improved control algorithm for real‐time substructure testing
Authors: Darby A. P. , Blakeborough A. , Williams M. S.
Published: September 2002

Real‐time substructure testing is a novel method of testing structures under dynamic loading. The complete structure is separated into two substructures, one of which is tested physically at large scale and in real time, so that time‐dependent non‐linear behaviour of the substructure is realistically represented. The second substructure represents the surrounding structure, which is modelled numerically. In the current formulation this numerical substructure is assumed to remain linear. The two substructures interact in real‐time so that the response of the complete structure, incorporating the non‐linear behaviour of the physical substructure, is accurately represented. This paper presents several improvements to the linear numerical modelling of substructures for use in explicit time‐stepping routines for real‐time substructure testing. An extrapolation of a first‐order‐hold discretization is used which increases the accuracy of the numerical model over more direct explicit methods. Additionally, an integral form of the equation of motion is used in order to reduce the effects of noise and to take into account variations of the input over a time‐step. In order to take advantage of this integral form, interpolation of the model output is performed in order to smooth the output. The improvements are demonstrated using a series of substructure tests on a simple portal frame. While the testing approach is suitable for cases in which the physical substructure behaves non‐linearly, the results presented here are for fully linear systems. This enables comparisons to be made with analytical solutions, as well as with the results of tests based on the central difference method. Copyright © 2001 John Wiley & Sons, Ltd.
Molecular characterization of FRAXB and comparative common fragile site instability in cancer cells
Authors: Arlt Martin F. , Miller Diane E. , Beer David G. , Glover Thomas W.
Published: September 2002

The common fragile site, FRA3B, has been shown to be a site of frequent homozygous deletions in some cancers, resulting in loss of expression of the associated FHIT gene. It has been proposed that FHIT is a tumor suppressor gene that is inactivated as a result of the instability of FRA3B in tumorigenesis. More recently, deletions at other common fragile sites, FRA7G and FRA16D, have been identified in a small number of cancer cell lines. Here, we have mapped and molecularly characterized the frequently observed common fragile site FRAXB, located at Xp22.3. Like other common fragile sites, it spans a large genomic region of approximately 500 kb. Three known genes, including the microsomal steroid sulfatase locus (STS), map within the fragile site region. We examined FRAXB and four other fragile sites (FRA3B, FRA7G, FRA7H, FRA16D), and several associated genes, for deletions and aberrant transcripts in a panel of cancer cell lines and primary tumors. Deletions within FRAXB were seen in 4/27 (14.8%) of the primary tumors and cell lines examined. Three of the 21 (14.3%) cell lines examined were characterized by loss of expression of one or more FRAXB‐associated genes. Moreover, all of the fragile sites examined were characterized by genomic deletions within the fragile site regions in one or more tumors or cell lines, including FRAXB, which is not associated with any known tumor suppressor genes or activity. Our results further support the hypothesis that common fragile sites and their associated genes are, in general, unstable in some cancer cells.
Cytogenetic clues to breast carcinogenesis
Authors: Teixeira Manuel R. , Pandis Nikos , Heim Sverre
Published: September 2002

The somatic mutation theory of cancer maintains that tumorigenesis is driven by genetic alterations, many of which are visible cytogenetically. We have examined breast cancer by chromosome banding analysis after short‐term culturing of tumor cells and here review our findings in 322 karyotypically abnormal samples obtained since 1992 from 256 patients. The screening capabilities of this technique enabled us to identify several cytogenetic subgroups of breast cancer, to study the intratumor heterogeneity of breast carcinomas, and to compare primary tumors with their metastases. Using chromosome abnormalities as clonality markers, we could determine on an individual basis when multiple, ipsilateral or bilateral breast, tumors were independent de novo carcinomas and when they resulted from the spreading of a single malignant clone within one breast or from one breast to the other. The distribution of chromosomal breakpoints and genomic gains and losses is clearly nonrandom in breast cancer, something that can guide further investigations using molecular methods. Based on the total dataset, we propose a multipathway model of mammary carcinogenesis that takes into consideration the genetic heterogeneity revealed by the karyotypic findings and review the karyotypic‐pathologic correlations and the possible clinical applications of the cytogenetic knowledge.
Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors
Authors: Miller Carl W. , Ikezoe Takayuki , Krug Utz , Hofmann Wolf‐K. , Tavor Sigal , Vegesna Vijaya , Tsukasaki Kunihiro , Takeuchi Seisho , Koeffler H. Phillip
Published: September 2002

Checkpoint genes, activated in response to DNA damage and other stresses, are frequently targeted for alteration in cancer. Checkpoint kinase 2 (CHK2, CDS1, RAD53) is activated by ataxia telangiectasia mutated (ATM) in response to γ irradiation. Activated CHK2 stabilizes TP53, and acts on other cell cycle and stress regulators. These findings place CHK2 in the middle of a pathway frequently targeted in cancer. Because of this, and the observation that CHK2 mutations are inherited in some Li‐Fraumeni cancer syndrome families, we decided to examine the role of CHK2 mutations in sporadic cancers. Exploiting the genomic sequence of chromosome 22, we looked for mutations in the exons and intron junctions of the CHK2 gene in DNA samples from 170 patients (57 osteosarcomas, 25 other sarcomas, 35 nonsmall‐cell lung, 20 ovarian, and 33 breast cancers). Missense mutations affecting the forkhead and kinase domains were detected in four osteosarcomas and in one ovarian and one lung cancer. These findings of CHK2 gene mutations are consistent with osteosarcoma being a defining tumor of Li‐Fraumeni syndrome. The occurrence of CHK2 mutations in sporadic cancers emphasizes the importance of the stress pathway which includes TP53.
Recurrence of OTT–MAL fusion in t(1;22) of infant AML‐M7
Authors: Mercher Thomas , Busson‐Le Coniat Maryvonne , Khac Florence Nguyen , Ballerini Paola , Mauchauffé Martine , Bui Hung , Pellegrino Béatrice , Radford Isabelle , Valensi Françoise , Mugneret Francine , Dastugue Nicole , Bernard Olivier A. , Berger Roland
Published: September 2002

Translocation t(1;22)(p13;q13) is associated with a peculiar subtype of acute megakaryocytic leukemia (M7) occurring in infants. We have recently characterized a fusion gene, OTT–MAL, resulting from this translocation. We now report three additional cases and show that this gene fusion is present in all five t(1;22) cases studied to date. Nucleotide sequence analysis of two translocation breakpoints suggests a nonhomologous end joining mechanism in the genesis of this translocation and reveals a noncanonical topoisomerase II‐like consensus sequence within the OTT gene. FISH and PCR techniques described in this work are useful for identifying t(1;22) associated with M7.
Identification of candidate liver tumor suppressor genes from human 11p11.2‐p12
Authors: Ricketts Sharon L. , Garcia Nicole F. , Betz Bryan L. , Coleman William B.
Published: September 2002

We have previously described a functional model for identification of human liver tumor suppressor genes in which human chromosome 11 was introduced into rat liver epithelial tumor cell lines via microcell‐mediated chromosome transfer, producing microcell hybrid (MCH) cell lines that exhibit suppression of tumorigenicity in vivo. Chromosome deletion mapping studies identified a 950‐kb region of 11p11.2‐p12 that was retained in all suppressed MCH cell lines, suggesting that this region may harbor one or more genes with liver tumor suppressor function. In this study, we generated a comprehensive transcription map of the 11p11.2‐p12 liver tumor suppressor region through examination of 142 expressed sequence tag (EST) markers among a group of suppressed MCH cell lines. Of 142 ESTs examined, 19 were localized within the 11p11.2‐p12 liver tumor suppressor region. RT‐PCR analysis of gene expression for these 19 ESTs among an index panel of suppressed MCH cell lines (n = 3) identified 11 potential candidate liver tumor suppressor genes. Examination of candidate gene expression among six additional suppressed MCH cell lines reduced the number of potential candidate genes to three (stSG30184, stSG10014, and stSG29748). Northern blot analysis of suppressed MCH cell lines and derived tumor cell lines suggested stSG30184 as the best candidate liver tumor suppressor gene. The 3.7 kb stSG30184 transcript was expressed by all suppressed MCH cell lines, but expression was extinguished coordinately with reexpression of tumorigenicity by these cells, consistent with a tumor suppressor gene. Subsequent characterization of this EST indicates that it is a novel transcript with expression in a broad range of tissue types. Further characterization of the genes identified in this study will provide a greater understanding of their role in the molecular pathogenesis of neoplastic liver disease.
Identification and functional characterization of the promoter region of the human MSH6 gene
Authors: Szadkowski Marta , Jiricny Josef
Published: September 2002

Postreplicative mismatch repair (MMR) corrects polymerase errors arising during DNA replication. Consistent with this role, the Saccharomyces cerevisiae MMR genes MSH2, MSH6, and PMS1 were reported to be transcriptionally upregulated during late G1 phase of the cell cycle. Surprisingly, despite the high degree of conservation of the MMR system in evolution, the human MMR genes studied to date, MSH2, MLH1, and PMS2, appear to be transcribed from classical housekeeping promoters, and the amounts of the polypeptides encoded by them fluctuate little during the cell cycle. Only the amounts of the 160‐kDa MSH6 protein were reported to vary, both during development and following stimulation of cell growth. Moreover, transcription of this gene was found to be downregulated by CpG methylation of the promoter region in a subset of clones treated with alkylating agents. In an attempt to understand the molecular basis underlying these phenomena, we isolated the 5′ region of the MSH6 gene and subjected it to functional analysis. We now show that the MSH6 gene is also transcribed from a classical housekeeping gene promoter. Despite housing putative binding sites for the transcription factors AP1, NF‐κB, and MTF‐1, the MSH6 promoter failed to respond to ionizing radiation or heavy metals. Interestingly, MSH6 transcription was upregulated during late G1 phase, even though the levels of the protein remained essentially constant during the cell cycle.
Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using m‐FISH
Authors: Van Limbergen Heidi , Poppe Bruce , Michaux Lucienne , Herens Christian , Brown Jill , Noens Luc , Berneman Zwi , De Bock Robrecht , De Paepe Anne , Speleman Frank
Published: September 2002

Complex chromosomal aberrations (CCAs) can be detected in a substantial proportion of AML and MDS patients, de novo as well as secondary or therapy‐related, and are associated with an adverse prognosis. Comprehensive analysis of the chromosomal rearrangements in these complex karyotypes has been hampered by the limitations of conventional cytogenetics. As a result, our knowledge concerning the cytogenetics of these malignancies is sparse. Here we describe a multiplex‐FISH (M‐FISH) study of CCAs in 36 patients with AML and MDS. M‐FISH generated a genome‐wide analysis of chromosomal aberrations in CCAs, establishing several cytogenetic subgroups. ‐5/5q‐ was demonstrated in the majority of patients (86%). Other rearrangements (present with or without ‐5/5q‐) included: deletion of 7q (47%), 3q rearrangements (19%), and MLL copy gain or amplification (17%). These genetic subgroups seem to display biological heterogeneity: MLL copy gain or amplification in association with 5q‐ was detected only in AML patients and was significantly associated with extremely short survival (median overall survival: 30 days, P = 0.0102). A partially cryptic t(4;5)(q31;q31), a balanced t(1;8)(p31;q22), and an unbalanced der(7)t(7;14)(q21;q13) were detected as possible new recurrent rearrangements in association with CCAs. Novel reciprocal translocations included t(5;11)(q33;p15)del(5)(q13q31) and t(3;6)(q26;q25). We conclude that AML and MDS with CCAs can be subdivided into molecular cytogenetic subclasses, which could reflect different clinical behavior and prognosis, and that three recurrent chromosomal aberrations are associated with karyotype complexity. © 2002 Wiley‐Liss, Inc.
Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15–20% of cases
Authors: Maserati Emanuela , Aprili Fiorenza , Vinante Fabrizio , Locatelli Franco , Amendola Giovanni , Zatterale Adriana , Milone Giuseppe , Minelli Antonella , Bernardi Franca , Lo Curto Francesco , Pasquali Francesco
Published: September 2002

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA‐stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA‐stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia‐positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15–20%.
Comparative genomic hybridization detects genetic alterations during early stages of cervical cancer progression
Authors: Umayahara Kenji , Numa Fumitaka , Suehiro Yutaka , Sakata Aki , Nawata Shugo , Ogata Hidenobu , Suminami Yoshinori , Sakamoto Masaru , Sasaki Kohsuke , Kato Hiroshi
Published: September 2002

Invasive cervical carcinoma is thought to arise from cervical intraepithelial neoplasm (CIN). Genetic changes that occur during progression of CIN to cervical carcinoma are poorly understood, although they appear to be directly involved in this process. We used comparative genomic hybridization (CGH) with precise microdissection and degenerate oligonucleotide primed‐polymerase chain reaction (DOP‐PCR) to detect genetic alterations in normal epithelial, CIN, and invasive carcinoma tissues colocalized in tumors from 18 patients with squamous cell carcinoma of the uterine cervix. Gains on chromosome 1 and on 3q and losses on 2q, 3p, 4, 6p, 11q, and 17p were frequent alterations found in CIN and invasive carcinoma lesions. Interestingly, several of these genetic changes were observed in preinvasive carcinoma lesions. The frequency and average number of genetic alterations corresponded directly to the extent to which the cervical carcinoma had progressed. Frequent alterations were found in more than 90% of CIN III lesions. Gains on 3q and losses on 11q were the most prevalent genetic alterations found in association with uterine cervix carcinogenesis. The common regions of alteration were 3q26.1‐q28 and 11q23‐qter. The majority of tumor samples showed variability in genetic alterations across lesion types within a single specimen.
Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability
Authors: Shimizu Yosuke , Ikeda Satoshi , Fujimori Masahiko , Kodama Shinya , Nakahara Masahiro , Okajima Masazumi , Asahara Toshimasa
Published: September 2002

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and β‐catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alteration of the components in the Wnt signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has not been elucidated. In order to assess the status of the Wnt signaling components in CRC with MSI, mutational analyses of the β‐catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the β‐catenin gene and two in the APC gene. Eight mutations in seven samples were detected by single‐strand conformation polymorphism and subsequent direct sequence analysis of the entire coding region of the Axin 1 gene. Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine‐ adenine repeat, (A)9) in its C‐terminal region, was mutated in 13 of the 33 samples. Thus, alteration in the Wnt signaling pathway is frequently observed in CRC with MSI, including hereditary nonpolyposis colorectal cancer, as well as in familial adenomatous polyposis and sporadic CRC without MSI. © 2002 Wiley‐Liss, Inc.
A framework for continuous design of production systems and its application in collective redesign of production line equipment
Authors: Darses Françoise
Published: September 2002

The continuous design of production systems is a major challenge facing companies, and one that requires organization and systematization. This article describes one of the continuous design endeavors implemented in a factory manufacturing steel tubes. We have studied the collective redesign of production line equipment. For 2 years, we followed the operations of a multioccupational group composed of the various actors involved in manufacturing (including the operators). Their task was to redesign the tools used in their production line.

Our analysis is focused on the cognitive side of the activity and especially on the collective redesign processes. From the transcripts of the meetings, we have examined how the codesigners come to an agreement about the redesigned equipment. We show that the criteria spontaneously used for the evaluation of the solution are far wider (quantitatively and qualitatively) than the list of functional criteria prescribed to the codesigners for the decision‐making process. This analysis leads us to propose three conditions that have to be met to guarantee success: (a) a true systemic view of the production system must be developed by all the continuous design actors, (b) there must be support for the collective decision‐making process, and (c) new forms of knowledge must be institutionalized. © 2002 John Wiley & Sons, Inc.