bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiferromagnetically coupled CoFeB∕Ru∕CoFeB trilayers
Authors: Wiese N. , Dimopoulos T. , Rührig M. , Wecker J. , Brückl H. , Reiss G.
Published: September 2004

This work reports on the magnetic interlayer coupling between two amorphous CoFeB layers, separated by a thin Ru spacer. We observe an antiferromagnetic coupling which oscillates as a function of the Ru thickness x, with the second antiferromagnetic maximum found for x=1.0–1.1nm. We have studied the switching of a CoFeB∕Ru∕CoFeB trilayer for a Ru thickness of 1.1nm and found that the coercivity depends on the net magnetic moment, i.e., the thickness difference of the two CoFeB layers. The antiferromagnetic coupling is almost independent of the annealing temperatures up to 300°C while an annealing at 350°C reduces the coupling and increases the coercivity, indicating the onset of crystallization. Used as a soft electrode in a magnetic tunnel junction, a high tunneling magnetoresistance of about 50%, a well-defined plateau and a rectangular switching behavior is achieved.
Exciton spin relaxation dynamics in InGaAs∕InP quantum wells
Authors: Akasaka Shunsuke , Miyata Shogo , Kuroda Takamasa , Tackeuchi Atsushi
Published: September 2004

We have investigated the exciton spin relaxation mechanism between 13 and 300K in InGaAs∕InP quantum wells using time-resolved spin-dependent pump and probe absorption measurements. The exciton spin relaxation time, τs above 40K was found to depend on temperature, T, according to τs∝T−1.1, although the spin relaxation time is constant below 40K. The clear carrier density dependence of the exciton spin relaxation time was observed below 40K, although the carrier density dependence is weak above 40K. These results imply that the main spin relaxation mechanism above and below 40K are the D’yakonov–Perel’ process and the Bir–Aronov–Pikus process, respectively.
Differential Hall effect profiling of ultrashallow junctions in Sb implanted silicon
Authors: Alzanki T. , Gwilliam R. , Emerson N. , Sealy B. J.
Published: September 2004

A differential Hall effect technique has been developed to obtain doping profiles at a depth resolution down to 2nm with junction depths of about 20nm. We have determined the electrical characteristics of 5×1014Sb+cm−2 implanted in (100) silicon at an energy of 5keV. A comparison was made between carrier concentration profiles and secondary ion mass spectroscopy measurements of the atomic profiles as a function of annealing temperature. We have profiled single energy implants of antimony and also double implants; the latter enables complete profiles to be measured down to the background level of about 1018cm−3.
Microfluidic design rules for capillary slot-based electrospray sources
Authors: Brinkmann M. , Blossey R. , Arscott S. , Druon C. , Tabourier P. , Le Gac S. , Rolando C.
Published: September 2004

We formulate microfluidic design principles for electrospray ionization sources based on a rectangular capillary slot formed by two triangular cantilevers. Spontaneous imbibition of the test liquids into the slot by capillary action provides a robust mechanism for liquid transport from a reservoir to the cantilever tip where an electrospray is generated upon application of a voltage. The correct functioning of the source requires the liquid bridging the slot to have a negative Laplace pressure. Imbibition is controlled by the ratio of slot width to height w∕h and the intrinsic contact angles θw, θs of the liquid with the slot walls and the cantilever faces, respectively. Based on these parameters we derive a simple criterion for the complete filling of the slot.
Efficient generation of noninductive, off-axis, Ohkawa current, driven by electron Bernstein waves in high β, spherical torus plasmas
Authors: Taylor G. , Efthimion P. C. , Kessel C. E. , Harvey R. W. , Smirnov A. P. , Ershov N. M. , Carter M. D. , Forest C. B.
Published: September 2004

Off-axis rf-driven current can play a critical role in sustaining high β, spherical torus (ST) plasmas without a central solenoid. Numerical modeling of electron Bernstein wave current drive (EBWCD) for a β∼40% ST plasma predicts efficient, off-axis, Ohkawa EBWCD. Current can be efficiently driven at r/a>0.5 where the large trapped electron fraction precludes conventional Fisch-Boozer current drive and provides favorable conditions for Ohkawa EBWCD. Calculated normalized current drive efficiency increases with r/a and is a factor of 2 higher at r/a=0.7 than has been obtained with electron cyclotron current drive near the axis of large aspect ratio tokamaks.
Cocaine-induced potentiation of synaptic strength in dopamine neurons: Behavioral correlates in GluRA(–/–) mice
Authors: Dong Y. , Saal D. , Thomas M. , Faust R. , Bonci A. , Robinson T. , Malenka R. C.
Published: September 2004

Synaptic plasticity in the mesolimbic dopamine (DA) system is thought to contribute to the neural adaptations that mediate behavioral sensitization, a model for core aspects of addiction. Recently, it has been demonstrated that multiple classes of drugs of abuse, as well as acute stress, enhance strength at excitatory synapses on midbrain DA neurons. Here, we show that both the cocaine- and stress-induced synaptic enhancement involves an up-regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This enhancement requires the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluRA as evidenced by its absence in mice lacking this subunit. The cocaine-elicited, but not the stress-elicited, synaptic potentiation in DA neurons was blocked by a D1-like receptor antagonist, indicating that thein vivotriggering mechanisms differ for these forms of experience-dependent synaptic modification. Surprisingly, behavioral sensitization to cocaine was elicited in GluRA(–/–) mice, indicating that potentiation of excitatory synaptic transmission in DA neurons is not necessary for this form of behavioral plasticity. However, GluRA(–/–) mice did not exhibit a conditioned locomotor response when placed in a context previously paired with cocaine, nor did they exhibit conditioned place preference in response to cocaine. We suggest that the drug-induced enhancement of excitatory synaptic transmission in midbrain DA neurons, although not required for behavioral sensitizationper se, may contribute to the attribution of incentive value to drug-associated cues.
Genetic exchange and plasmid transfers in
Borrelia burgdorferi sensu stricto
revealed by three-way genome comparisons and multilocus sequence typing
Authors: Qiu Wei-Gang , Schutzer Steven E. , Bruno John F. , Attie Oliver , Xu Yun , Dunn John J. , Fraser Claire M. , Casjens Sherwood R. , Luft Benjamin J.
Published: September 2004

Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of
Borrelia burgdorferi sensu stricto
, the causative agent of Lyme disease, and we compared the predicted genes from the two genomes with those from the previously sequenced B31 genome. The three genomes are closely related and are evolutionarily approximately equidistant (≈0.5% pairwise nucleotide differences on the main chromosome). We used a Poisson model of nucleotide substitution to screen for genes with elevated levels of nucleotide polymorphisms. The three-way genome comparison allowed distinction between polymorphisms introduced by mutations and those introduced by recombination using the method of phylogenetic partitioning. Tests for recombination suggested that patches of high-density nucleotide polymorphisms on the chromosome and plasmids arise by DNA exchange. The role of recombination as the main mechanism driving
B. burgdorferi
diversification was confirmed by multilocus sequence typing of 18 clinical isolates at 18 polymorphic loci. A strong linkage between the multilocus sequence genotypes and the major alleles of outer-surface protein C (
ospC
) suggested that balancing selection at
ospC
is a dominant force maintaining
B. burgdorferi
diversity in local populations. We conclude that
B. burgdorferi
undergoes genome-wide genetic exchange, including plasmid transfers, and previous reports of its clonality are artifacts from the use of geographically and ecological isolated samples. Frequent recombination implies a potential for rapid adaptive evolution and a possible polygenic basis of
B. burgdorferi
pathogenicity.
Characterization of the ERβ
–
/–mouse heart
Authors: Förster Carola , Kietz Silke , Hultenby Kjell , Warner Margaret , Gustafsson Jan-Åke
Published: September 2004

Although the heart responds to estrogen, it is not clear whether estrogen acts directly on heart muscle or indirectly by means of the vascular, immune, or nervous system. No role for estrogen receptor (ER) β in the heart has been established, but ERβ
–/–
mice are hypertensive, and as they age, their hearts become enlarged. Histological and ultrastructural analysis of the heart revealed a disarray of myocytes, a disruption of intercalated discs, an increase in the number and size of gap junctions, and a profound alteration in nuclear structure, concomitantly with a loss of expression of lamin A/C from the nuclear envelope. In the lungs of ERβ
–/–
mice, lamin A/C was located in the nuclear membrane, indicating that lamin A/C is not an ERβ-regulated gene. Immunohistochemical studies with ERβ antibodies failed to detect ERβ in the myocardium. We conclude that abnormalities in heart morphology in ERβ
–/–
mice are likely due to stress on the nuclear envelope as a result of the chronic sustained systolic and diastolic hypertension observed in ERβ
–/–
mice. Because neither ERα nor ERβ could be detected in heart muscle, the effects of estrogen on the myocardium seem to be indirect.
The c-Jun NH
2
-terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis
Authors: Weston Claire R. , Wong Anthony , Hall J. Perry , Goad Mary E. P. , Flavell Richard A. , Davis Roger J.
Published: September 2004

The c-Jun NH
2
-terminal kinase (JNK) group of mitogen-activated protein kinases is activated in response to a wide array of cellular stresses and proinflammatory cytokines. Roles for JNK in the developing nervous system and T-cell-mediated immunity have been established by detailed studies of mice with compound mutations in the
Jnk
genes. However, little is known concerning the roles of JNK in other mammalian tissues. Mice lacking both of the ubiquitously expressed isoforms (JNK1 and -2) die during midgestation with neural tube closure defects and brain abnormalities. Here we show that JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, and lungs. In addition, JNK-deficient mice exhibit an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF. We further demonstrate that adult mice lacking either JNK1 or -2 display striking differences in epidermal proliferation and differentiation, indicative of distinct roles for these kinases in the skin. We conclude that JNK is necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis.
MutS inhibits RecA-mediated strand exchange with platinated DNA substrates
Authors: Calmann Melissa A. , Marinus M. G.
Published: September 2004

Human cell lines and
Escherichia coli dam
mutants are sensitive to the cytotoxic action of the anticancer agent, cisplatin. Introduction of mutations disabling DNA mismatch repair into these cell lines renders them resistant to the action of this drug. We used RecA-mediated strand exchange between homologous phiX174 molecules, one that was platinated and the other that was unmodified, to show that strand transfer is decreased in a dose-dependent manner. Transfer was severely decreased at 10 adducts per molecule (5,386 bp) and abolished with 24 adducts. At low levels of adduction, addition of MutS to the reaction further decreases the rate and yield in a dose-dependent manner. MutL addition was without effect even in the presence of MutS. The results suggest that although mismatch repair is beneficial for mutation avoidance, its antirecombination activity on inappropriate substrates can be lethal to the cell.
The human
BCL6
transgene promotes the development of lymphomas in the mouse
Authors: Baron Beverly W. , Anastasi John , Montag Anthony , Huo Dezheng , Baron Rebecca M. , Karrison Theodore , Thirman Michael J. , Subudhi Sumit K. , Chin Robert K. , Felsher Dean W. , Fu Yang-Xin , McKeithan Timothy W. , Baron Joseph M.
Published: September 2004

BCL6
, a gene on chromosome 3, band q27, encodes a zinc finger transcriptional repressor that is needed for germinal center formation and has been implicated in the pathogenesis of some human lymphomas when it is mutated or involved in chromosomal rearrangements. To explore further the mechanisms of action of BCL6 in lymphomagenesis, we developed a transgenic mouse model mimicking a common translocation, the t(3, 14)(q27;q32), in human lymphomas. The transgenic mice develop normally and express the transgenic BCL6 protein constitutively in lymphocytes. A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of
N
-ethyl-
N
-nitrosourea, a carcinogen that induces DNA mutations. The
N
-ethyl-
N
-nitrosourea-induced lymphomas spread widely, were exclusively T cell, expressed the BCL6 protein, and occurred only in the transgenic mice. Because BCL6 expression has been reported in a number of T cell tumors as well as in the more commonly occurring B cell lymphomas in humans, our transgenic mice provide a model for the study of human lymphomas.
Activities of the Matrix Metalloproteinase Stromelysin-2 (MMP-10) in Matrix Degradation and Keratinocyte Organization in Wounded Skin
Authors: Krampert Monika , Bloch Wilhelm , Sasaki Takako , Bugnon Philippe , Rülicke Thomas , Wolf Eckhard , Aumailley Monique , Parks William C. , Werner Sabine
Published: September 2004

The matrix metalloproteinase stromelysin-2 is expressed in keratinocytes of the epithelial tongue of skin wounds, suggesting a role in keratinocyte migration. Here, we show that stromelysin-2 enhances migration of cultured keratinocytes. To gain insight into the in vivo activities of stromelysin-2 in epithelial repair, we generated transgenic mice expressing a constitutively active stromelysin-2 mutant in keratinocytes. These animals had no alterations in skin architecture, and the healing rate of skin wounds was normal. Histologically, however, we found abnormalities in the organization of the wound epithelium. Keratinocytes at the migrating epidermal tip were scattered in most sections of mice with high expression level, and there was a reduced deposition of new matrix. In particular, the staining pattern of laminin-5 at the wound site was altered. This may be due to proteolytic processing of laminin-5 by stromelysin-2, because degradation of laminin-5 by this enzyme was observed in vitro. The inappropriate matrix contact of keratinocytes was accompanied by aberrant localization of β1-integrins and phosphorylated focal adhesion kinase, as well as by increased apoptosis of wound keratinocytes. These results suggest that a tightly regulated expression level of stromelysin-2 is required for limited matrix degradation at the wound site, thereby controlling keratinocyte migration.
Clann: investigating phylogenetic information through supertree analyses
Authors: Creevey C. J. , McInerney J. O.
Published: September 2004

Summary: Clann has been developed in order to provide methods of investigating phylogenetic information through the application of supertrees.

Availability: Clann has been precompiled for Linux, Apple Macintosh and Windows operating systems and is available from http://bioinf.may.ie/software/clann. Source code is available on request from the authors.

Supplementary information: Clann has been written in the C programming language. Source code is available on request.

Contact:  chris.creevey@may.ie
Iterative Cluster Analysis of Protein Interaction Data
Authors: Arnau Vicente , Mars Sergio , Marín Ignacio
Published: September 2004

Motivation: Generation of fast tools of hierarchical clustering to be applied when distances among elements of a set are constrained, causing frequent distance ties, as happens in protein interaction data.

Results: We present in this work the program UVCLUSTER, that iteratively explores distance datasets using hierarchical clustering. Once the user selects a group of proteins, UVCLUSTER converts the set of primary distances among them (i.e. the minimum number of steps, or interactions, required to connect two proteins) into secondary distances that measure the strength of the connection between each pair of proteins when the interactions for all the proteins in the group are considered. We show that this novel strategy has advantages over conventional clustering methods to explore protein–protein interaction data. UVCLUSTER easily incorporates the information of the largest available interaction datasets to generate comprehensive primary distance tables. The versatility, simplicity of use and high speed of UVCLUSTER on standard personal computers suggest that it can be a benchmark analytical tool for interactome data analysis.

Availability: The program is available upon request from the authors, free for academic users. Additional information available at http://www.uv.es/genomica/UVCLUSTER

Contact:  ignacio.marin@uv.es
An experimental evaluation of a loop versus a reference design for two-channel microarrays
Authors: Vinciotti V. , Khanin R. , D'Alimonte D. , Liu X. , Cattini N. , Hotchkiss G. , Bucca G. , de Jesus O. , Rasaiyaah J. , Smith C. P. , Kellam P. , Wit E.
Published: September 2004

Motivation: Despite theoretical arguments that so-called ‘loop designs’ for two-channel DNA microarray experiments are more efficient, biologists continue to use ‘reference designs’. We describe two sets of microarray experiments with RNA from two different biological systems (TPA-stimulated mammalian cells and Streptomyces coelicolor). In each case, both a loop and a reference design were used with the same RNA preparations with the aim of studying their relative efficiency.

Results: The results of these experiments show that (1) the loop design attains a much higher precision than the reference design, (2) multiplicative spot effects are a large source of variability, and if they are not accounted for in the mathematical model, for example, by taking log-ratios or including spot effects, then the model will perform poorly. The first result is reinforced by a simulation study. Practical recommendations are given on how simple loop designs can be extended to more realistic experimental designs and how standard statistical methods allow the experimentalist to use and interpret the results from loop designs in practice.

Availability: The data and R code are available at http://exgen.ma.umist.ac.uk

Contact:  veronica.vinciotti@brunel.ac.uk
VarMixt: efficient variance modelling for the differential analysis of replicated gene expression data
Authors: Delmar Paul , Robin Stéphane , Daudin Jean Jacques
Published: September 2004

Motivation: Identifying differentially regulated genes in experiments comparing two experimental conditions is often a key step in the microarray data analysis process. Many different approaches and methodological developments have been put forward, yet the question remains open.

Results: Varmixt is a powerful and efficient novel methodology for this task. It is based on a flexible and realistic variance modelling strategy. It compares favourably with other popular techniques (standard t-test, SAM and Cyber-T). The relevance of the approach is demonstrated with real-world and simulated datasets. The analysis strategy was successfully applied to both a ‘two-colour’ cDNA microarray and an Affymetrix Genechip. Strong control of false positive and false negative rates is proven in large simulation studies.

Availability: The R package is freely available at http://www.inapg.inra.fr/ens_rech/mathinfo/recherche/mathematique/outil.html

Contact:  delmar@inapg.inra.fr

Supplementary information:  http://www.inapg.inra.fr/ens_rech/mathinfo/recherche/mathematique/outil.html
Prediction of splice sites with dependency graphs and their expanded bayesian networks
Authors: Chen Te-Ming , Lu Chung-Chin , Li Wen-Hsiung
Published: September 2004

Motivation: Owing to the complete sequencing of human and many other genomes, huge amounts of DNA sequence data have been accumulated. In bioinformatics, an important issue is how to predict the complete structure of genes from the genomic DNA sequence, especially the human genome. A crucial part in the gene structure prediction is to determine the precise exon–intron boundaries, i.e. the splice sites, in the coding region.

Results: We have developed a dependency graph model to fully capture the intrinsic interdependency between base positions in a splice site. The establishment of dependency between two position is based on a χ2-test from known sample data. To facilitate statistical inference, we have expanded the dependency graph (which is usually a graph with cycles that make probabilistic reasoning very difficult, if not impossible) into a Bayesian network (which is a directed acyclic graph that facilitates statistical reasoning).

When compared with the existing models such as weight matrix model, weight array model, maximal dependence decomposition, Cai et al.'s tree model as well as the less-studied second-order and third-order Markov chain models, the expanded Bayesian networks from our dependency graph models perform the best in nearly all the cases studied.

Availability: Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/

Contact:  cclu@ee.nthu.edu.tw
Identifying time-lagged gene clusters using gene expression data
Authors: Ji Liping , Tan Kian-Lee
Published: September 2004

Motivation: Analysis of gene expression data can provide insights into the time-lagged co-regulation of genes/gene clusters. However, existing methods such as the Event Method and the Edge Detection Method are inefficient as they compare only two genes at a time. More importantly, they neglect some important information due to their scoring criterian. In this paper, we propose an efficient algorithm to identify time-lagged co-regulated gene clusters. The algorithm facilitates localized comparison and processes several genes simultaneously to generate detailed and complete time-lagged information for genes/gene clusters.

Results: We experimented with the time-series Yeast gene dataset and compared our algorithm with the Event Method. Our results show that our algorithm is not only efficient, but also delivers more reliable and detailed information on time-lagged co-regulation between genes/gene clusters.

Availability: The software is available upon request.

Contact:  jiliping@comp.nus.edu.sg

Supplementary information: Supplementary tables and figures for this paper can be found at http://www.comp.nus.edu.sg/~jiliping/p2.htm.
Statistical methods of translating microarray data into clinically relevant diagnostic information in colorectal cancer
Authors: Kim Byung Soo , Kim Inyoung , Lee Sunho , Kim Sangcheol , Rha Sun Young , Chung Hyun Cheol
Published: September 2004

Motivation: It is a common practice in cancer microarray experiments that a normal tissue is collected from the same individual from whom the tumor tissue was taken. The indirect design is usually adopted for the experiment that uses a common reference RNA hybridized both to normal and tumor tissues. However, it is often the case that the test material is not large enough for the experimenter to extract enough RNA to conduct the microarray experiment. Hence, collecting ncases does not necessarily end up with a matched pair sample of size n. Instead we usually have a matched pair sample of size n1, and two independent samples of sizes n2 and n3, respectively, for ‘reference versus normal tissue only’ and ‘reference versus tumor tissue only’ hybridizations (n = n1 + n2 + n3). Standard statistical methods need to be modified and new statistical procedures are developed for analyzing this mixed dataset.

Results: We propose a new test statistic, t3, as a means of combining all the information in the mixed dataset for detecting differentially expressed (DE) genes between normal and tumor tissues. We employed the extended receiver operating characteristic approach to the mixed dataset. We devised a measure of disagreement between a RT–PCR experiment and a microarray experiment. Hotelling's T2 statistic is employed to detect a set of DE genes and its prediction rate is compared with the prediction rate of a univariate procedure. We observe that Hotelling's T2 statistic detects DE genes more efficiently than a univariate procedure and that further research is warranted on the formal test procedure using Hotelling's T2 statistic.

Contact:  bskim@yonsei.ac.kr
ESTminer: a Web interface for mining EST contig and cluster databases
Authors: Huang Yecheng , Pumphrey Janie , Gingle Alan R.
Published: September 2004

Summary: ESTminer is a Web application and database schema for interactive mining of expressed sequence tag (EST) contig and cluster datasets. The Web interface contains a query frame that allows the selection of contigs/clusters with specific cDNA library makeup or a threshold number of members. The results are displayed as color-coded tree nodes, where the color indicates the fractional size of each cDNA library component. The nodes are expandable, revealing library statistics as well as EST or contig members, with links to sequence data, GenBank records or user configurable links. Also, the interface allows ‘queries within queries’ where the result set of a query is further filtered by the subsequent query.

Availability: ESTminer is implemented in Java/JSP and the package, including MySQL and Oracle schema creation scripts, is available from http://cggc.agtec.uga.edu/Data/download.asp

Contact:  agingle@uga.edu
A semiparametric approach for marker gene selection based on gene expression data
Authors: Guan Zhong , Zhao Hongyu
Published: September 2004

Motivation: Identification of differentially expressed genes is a major issue in gene expression data analysis and selection of marker genes is critical in tumor classification using gene expression data. In this paper, we propose a semiparametric two-sample test to identify both differentially expressed genes and select marker genes for sample classification.

Results: A simulation study shows that the proposed method is more robust and powerful than the methods, generally used such as t-tests and non-parametric rank-sum tests, when the sample size is small. Cross-validation shows that the sample classification based on genes selected using this semiparametric method has lower misclassification rates.

Contact:  hongyu.zhao@yale.edu
A comprehensive evaluation of multicategory classification methods for microarray gene expression cancer diagnosis
Authors: Statnikov Alexander , Aliferis Constantin F. , Tsamardinos Ioannis , Hardin Douglas , Levy Shawn
Published: September 2004

Motivation: Cancer diagnosis is one of the most important emerging clinical applications of gene expression microarray technology. We are seeking to develop a computer system for powerful and reliable cancer diagnostic model creation based on microarray data. To keep a realistic perspective on clinical applications we focus on multicategory diagnosis. To equip the system with the optimum combination of classifier, gene selection and cross-validation methods, we performed a systematic and comprehensive evaluation of several major algorithms for multicategory classification, several gene selection methods, multiple ensemble classifier methods and two cross-validation designs using 11 datasets spanning 74 diagnostic categories and 41 cancer types and 12 normal tissue types.

Results: Multicategory support vector machines (MC-SVMs) are the most effective classifiers in performing accurate cancer diagnosis from gene expression data. The MC-SVM techniques by Crammer and Singer, Weston and Watkins and one-versus-rest were found to be the best methods in this domain. MC-SVMs outperform other popular machine learning algorithms, such as k-nearest neighbors, backpropagation and probabilistic neural networks, often to a remarkable degree. Gene selection techniques can significantly improve the classification performance of both MC-SVMs and other non-SVM learning algorithms. Ensemble classifiers do not generally improve performance of the best non-ensemble models. These results guided the construction of a software system GEMS (Gene Expression Model Selector) that automates high-quality model construction and enforces sound optimization and performance estimation procedures. This is the first such system to be informed by a rigorous comparative analysis of the available algorithms and datasets.

Availability: The software system GEMS is available for download from http://www.gems-system.org for non-commercial use.

Contact:  alexander.statnikov@vanderbilt.edu
Reliability analysis of microarray data using fuzzy c-means and normal mixture modeling based classification methods
Authors: Asyali Musa H. , Alci Musa
Published: September 2004

Motivation: A serious limitation in microarray analysis is the unreliability of the data generated from low signal intensities. Such data may produce erroneous gene expression ratios and cause unnecessary validation or post-analysis follow-up tasks. Therefore, the elimination of unreliable signal intensities will enhance reproducibility and reliability of gene expression ratios produced from microarray data. In this study, we applied fuzzy c-means (FCM) and normal mixture modeling (NMM) based classification methods to separate microarray data into reliable and unreliable signal intensity populations.

Results: We compared the results of FCM classification with those of classification based on NMM. Both approaches were validated against reference sets of biological data consisting of only true positives and true negatives. We observed that both methods performed equally well in terms of sensitivity and specificity. Although a comparison of the computation times indicated that the fuzzy approach is computationally more efficient, other considerations support the use of NMM for the reliability analysis of microarray data.

Availability: The classification approaches described in this paper and sample microarray data are available as MatlabTM (The MathWorks Inc., Natick, MA) programs (mfiles) and text files, respectively, at http://rc.kfshrc.edu.sa/bssc/staff/MusaAsyali/Downloads.asp. The programs can be run/tested on many different computer platforms where Matlab is available.

Contact:  asyali@kfshrc.edu.sa
Signaling via a novel integral plasma membrane pool of a serine/threonine protein kinase PRK1 in mammalian cells
Authors: Zhu Yimin , Stolz Donna B. , Guo Fengli , Ross Mark A. , Watkins Simon C. , Tan Bee Jen , Qi Robert Z. , Manser Ed , Li Qiu Tian , Bay Boon Huat , Teo Tian Seng , Duan Wei
Published: September 2004

Mammalian serine/threonine protein kinases, except for TGF‐β receptor kinase family, are intracellular proteins. PRK1/PKN is a member of the protein kinase C superfamily of serine/threonine kinases and is one of the first identified effectors for RhoA GTPase. However, the role of PRK1 in mediating signaling downstream of activated RhoA is largely unknown. Here, we present evidence that identifies a novel plasma membrane pool of PRK1. This integral membrane form of PRK1 is catalytically active. The phosphorylation of serine377 of PRK1 is required for its integration into membranes. This integration is essential for PRK1 to function as a Rho effector as only the integral plasma membrane PRK1 is able to initiate RhoA‐mediated and ligand‐dependent transcriptional activation of the androgen receptor in human epithelial cells and to mediate RhoA‐induced neurite retraction in mouse neuronal cells. These results indicate that RhoA signals via the integral membrane pool of its effectors in its immediate vicinity at the plasma membrane, thus establishing a new paradigm in mammalian cell signaling.
RETRACTED: 5‐Lipoxygenase antagonizes genotoxic stress‐induced apoptosis by altering p53 nuclear trafficking
Authors: Catalano Alfonso , Caprari Paola , Soddu Silvia , Procopio Antonio , Romano Mario
Published: September 2004

5‐Lipoxygenase (5‐LO) promotes cancer cell proliferation and survival by unclear mechanisms. Here, we show that 5‐LO expression and activity were induced by genotoxic agents in a p53‐independent manner and antagonized p53‐ or genotoxic drug‐induced apoptosis in a variety of cancer cells. 5‐LO inhibited p53‐governed transactivation of the pro‐apoptotic genes bax and pig3 but not of p21WAF1/CIP1 or mdm2. This may be explained by 5‐LO capability to inhibit the binding of p53 to promyelocytic leukemia protein (PML) and p53 subnuclear relocalization into PML‐nuclear bodies in response to genotoxic stress. Interestingly, 5‐LO activity appears to be involved in nuclear retention and inactivation of wild‐type p53 in malignant mesothelioma cells. In these cells, genetic or pharmacological inhibition of 5‐LO enabled suppression of in vitro tumorigenicity by low doses of chemotherapeutic drugs. Together, these results uncover novel functions of 5‐LO and contribute to the understanding of 5‐LO involvement in tumor progression. Moreover, they provide a rationale to the therapeutic use of 5‐LO inhibitors to enhance cancer chemosensitivity in selected tumors.
AtHKT1 Facilitates Na+ Homeostasis and K+ Nutrition in Planta
Authors: Rus Ana , Lee Byeong-ha , Muñoz-Mayor Alicia , Sharkhuu Altanbadralt , Miura Kenji , Zhu Jian-Kang , Bressan Ray A. , Hasegawa Paul M.
Published: September 2004

Genetic and physiological data establish that Arabidopsis AtHKT1 facilitates Na+ homeostasis in planta and by this function modulates K+ nutrient status. Mutations that disrupt AtHKT1 function suppress NaCl sensitivity of sos1-1 and sos2-2, as well as of sos3-1 seedlings grown in vitro and plants grown in controlled environmental conditions. hkt1 suppression of sos3-1 NaCl sensitivity is linked to higher Na+ content in the shoot and lower content of the ion in the root, reducing the Na+ imbalance between these organs that is caused by sos3-1. AtHKT1 transgene expression, driven by its innate promoter, increases NaCl but not LiCl or KCl sensitivity of wild-type (Col-0 gl1) or of sos3-1 seedlings. NaCl sensitivity induced by AtHKT1 transgene expression is linked to a lower K+ to Na+ ratio in the root. However, hkt1 mutations increase NaCl sensitivity of both seedlings in vitro and plants grown in controlled environmental conditions, which is correlated with a lower K+ to Na+ ratio in the shoot. These results establish that AtHKT1 is a focal determinant of Na+ homeostasis in planta, as either positive or negative modulation of its function disturbs ion status that is manifested as salt sensitivity. K+-deficient growth of sos1-1, sos2-2, and sos3-1 seedlings is suppressed completely by hkt1-1. AtHKT1 transgene expression exacerbates K+ deficiency of sos3-1 or wild-type seedlings. Together, these results indicate that AtHKT1 controls Na+ homeostasis in planta and through this function regulates K+ nutrient status.
Cellular and Subcellular Localization of Endogenous Nitric Oxide in Young and Senescent Pea Plants
Authors: Corpas Francisco J. , Barroso Juan B. , Carreras Alfonso , Quirós Miguel , León Ana M. , Romero-Puertas María C. , Esteban Francisco J. , Valderrama Raquel , Palma José M. , Sandalio Luisa M. , Gómez Manuel , del Río Luis A.
Published: September 2004

The cellular and subcellular localization of endogenous nitric oxide (NO ˙) in leaves from young and senescent pea (Pisum sativum) plants was studied. Confocal laser scanning microscopy analysis of pea leaf sections with the fluorescent probe 4,5-diaminofluorescein diacetate revealed that endogenous NO ˙ was mainly present in vascular tissues (xylem and phloem). Green fluorescence spots were also detected in the epidermal cells, palisade and spongy mesophyll cells, and guard cells. In senescent leaves, NO ˙ generation was clearly reduced in the vascular tissues. At the subcellular level, by electron paramagnetic resonance spectroscopy with the spin trap Fe(MGD)2 and fluorometric analysis with 4,5-diaminofluorescein diacetate, NO ˙ was found to be an endogenous metabolite of peroxisomes. The characteristic three-line electron paramagnetic resonance spectrum of NO ˙, with g = 2.05 and aN = 12.8 G, was detected in peroxisomes. By fluorometry, NO ˙ was also found in these organelles, and the level measured of NO ˙ was linearly dependent on the amount of peroxisomal protein. The enzymatic production of NO ˙ from l-Arg (nitric oxide synthase [NOS]-like activity) was measured by ozone chemiluminiscence. The specific activity of peroxisomal NOS was 4.9 nmol NO ˙ mg−1 protein min−1; was strictly dependent on NADPH, calmodulin, and BH4; and required calcium. In senescent pea leaves, the NOS-like activity of peroxisomes was down-regulated by 72%. It is proposed that peroxisomal NO ˙ could be involved in the process of senescence of pea leaves.
The Pepper Transcription FactorCaPF1Confers Pathogen and Freezing Tolerance in Arabidopsis
Authors: Yi So Young , Kim Jee-Hyub , Joung Young-Hee , Lee Sanghyeob , Kim Woo-Taek , Yu Seung Hun , Choi Doil
Published: September 2004

An ERF/AP2-type transcription factor (CaPF1) was isolated by differential-display reverse transcription-PCR, following inoculation of the soybean pustule pathogen Xanthomonas axonopodis pv glycines 8ra, which induces hypersensitive response in pepper (Capsicum annuum) leaves. CaPF1 mRNA was induced under conditions of biotic and abiotic stress. Higher levels of CaPF1 transcripts were observed in disease-resistant tissue compared with susceptible tissue. CaPF1 expression was additionally induced using various treatment regimes, including ethephon, methyl jasmonate, and cold stress. To determine the role of CaPF1 in plants, transgenic Arabidopsis and tobacco (Nicotiana tabacum) plants expressing higher levels of CaPF1 were generated. Gene expression analyses of transgenic Arabidopsis and tobacco revealed that the CaPF1 level in transgenic plants affects expression of genes that contain either a GCC or a CRT/DRE box in their promoter regions. Furthermore, transgenic Arabidopsis plants expressing CaPF1 displayed tolerance against freezing temperatures and enhanced resistance to Pseudomonas syringae pv tomato DC3000. Disease tolerance was additionally observed in CaPF1 transgenic tobacco plants. The results collectively indicate that CaPF1 is an ERF/AP2 transcription factor in hot pepper plants that may play dual roles in response to biotic and abiotic stress in plants.
X-ray diffuse scattering holography
Authors: Kopecký Miloš
Published: September 2004

It is shown that anomalous X-ray diffuse scattering can be treated as a hologram providing information on the local environment of the anomalous scatterer. In contrast with standard holography with atomic resolution, holographic oscillations of several percent of the total measured signal can be achieved by choosing suitable photon energies. The problem of virtual images can be solved very easily in the case of both centrosymmetric and non-centrosymmetric structures. Moreover, these holograms are not overlapped by dense and strong Kossel line patterns.
Observation of orientational disorder in the hexagonal stuffed tridymite Sr0.864Eu0.136Al2O4by the maximum-entropy method
Authors: Yamada H. , Shi W. S. , Xu C. N.
Published: September 2004

The crystal structure of a strontium europium aluminate, Sr0.864Eu0.136Al2O4, with a novel hexagonal form was investigated by a combination of Rietveld analysis and the maximum-entropy method (MEM) with synchrotron X-ray powder diffraction data. The electron density image calculated by the MEM/Rietveld method revealed that the apical oxygen ion in the AlO4tetrahedron has a broad distribution corresponding to an extraordinarily large atomic displacement parameter. This structure could be expressed by a split-atom model, with which the Rietveld refinement gaveRwp= 2.99% andRB= 4.16%. Subsequently, MEM-based pattern fitting (MPF) decreased theRfactors toRwp= 2.81% andRB= 2.34% and the electron density image clearly showed that the apical oxygen ions of the AlO4tetrahedra are split over three sites around a threefold axis involving an elongated distribution of the residual O ions along thecaxis. These results suggest that AlO4tetrahedra in Sr0.864Eu0.136Al2O4are orientationally disordered.
Powder pattern indexing with the dichotomy method
Authors: Boultif Ali , Louër Daniel
Published: September 2004

The efficiency of the successive dichotomy method for powder diffraction pattern indexing [Louër & Louër (1972).J. Appl. Cryst.5, 271–275] has been proved over more than 30 years of usage. Features implemented in the new version of the computer programDICVOL04 include (i) a tolerance to the presence of impurity (or inaccurately measured) diffraction lines, (ii) a refinement of the `zero-point' position, (iii) a reviewing of all input lines from the solution found from, generally, the first 20 lines, (iv) a cell analysis, based on the concept of the reduced cell, to identify equivalent monoclinic and triclinic solutions, and (v) an optional analysis of input powder data to detect the presence of a significant `zero-point' offset. New search strategies have also been introduced,e.g.each crystal system is scanned separately, within the input volume limits, to limit the risk of missing a solution characterized by a metric lattice singularity. The default values in the input file have been extended to 25 Å for the linear parameters and 2500 Å3for the cell volume. The search is carried out exhaustively within the input parameter limits and the absolute error on peak position measurements. Many tests with data from the literature and from powder data of pharmaceutical materials, collected with the capillary technique and laboratory monochromatic X-rays, have been performed with a high success rate, covering all crystal symmetries from cubic to triclinic. Some examples reported as `difficult' cases are also discussed. Additionally, a few recommendations for the correct practice of powder pattern indexing are reported.
Characterization and modelling of germanium assembled crystals for the diffraction of thermal neutrons
Authors: Alianelli Lucia , Sánchez del Río Manuel , Felici Roberto
Published: September 2004

Two assembled germanium crystals, produced for use as neutron monochromators, are characterized by means of neutron and X-ray diffraction. The neutron and synchrotron experimental data (reflectivity profiles and topographs) are compared with calculations based on analytical models and Monte Carlo simulations. Our results show the limits of the standard theories and indicate that full Monte Carlo simulations can be a valid tool for interpreting real crystal reflectivities.
Small-angle scattering from spherical core–shell particles: an analytical scattering function for particles with Schulz–Flory size distribution
Authors: Wagner Joachim
Published: September 2004

The scattering function for Schulz–Flory distributed spherical core–shell particles is derived analytically. A constant ratio of core to shell radii is assumed. The analytical expression, which does not require any numerical integration, provides a fast way to model experimental data by nonlinear least-squares fitting. The asymptotic behavior for large momentum transfers coincides with the different power laws expected for homogenous spheres and thin spherical shells. In the second part, the derived expression is applied to describe experimental small-angle X-ray scattering data from core–shell particles with different particle sizes, polydispersity and ratio of core to shell radii. For large particles, a resolution correction by numerical convolution with a Gaussian resolution function is applied.
Convergent-beam neutron crystallography
Authors: Gibson W. M. , Schultz A. J. , Richardson J. W. , Carpenter J. M. , Mildner D. F. R. , Chen-Mayer H. H. , Miller M. E. , Maxey E. R. , Youngman R.
Published: September 2004

Two monolithic polycapillary optics of different focal length and beam convergence are employed to investigate the use of focusing lenses for the neutron convergent-beam method for time-of-flight crystallography with a broad neutron wavelength bandwidth. The optic of short output focal length (15.5 mm) with a beam convergence of 16.8 (10)° has a focal spot diameter of ∼100 µm for 3.2 Å neutrons. For an MnF2single-crystal sample of this diameter on a pulsed neutron source, this lens gives an expected integrated intensity gain of ∼100 for a 020 Bragg peak. Further measurements on a powder diffractometer show that the expected diffracted beam intensities for Ni have gains in excess of 500 for powder samples of this diameter. The degradation of resolution is minimized in the backscattering geometry.
X-ray imaging with ultra-small-angle X-ray scattering as a contrast mechanism
Authors: Levine L. E. , Long G. G.
Published: September 2004

A new transmission X-ray imaging technique using ultra-small-angle X-ray scattering (USAXS) as a contrast mechanism is described. USAXS imaging can sometimes provide contrast in cases where radiography and phase-contrast imaging are unsuccessful. Images produced at different scattering vectors highlight different microstructural features within the same sample volume. When used in conjunction with USAXS scans, USAXS imaging provides substantial quantitative and qualitative three-dimensional information on the sizes, shapes and spatial arrangements of the scattering objects. The imaging technique is demonstrated on metal and biological samples.
Ab initiostructure determination of the Γ form ofD-sorbitol (D-glucitol) by powder synchrotron X-ray diffraction
Authors: Rukiah Mwaffak , Lefebvre Jacques , Hernandez Olivier , van Beek Wouter , Serpelloni Michel
Published: September 2004

A high-resolution powder synchrotron X-ray diffraction pattern of the Γ form of D-sorbitol has been recorded at 293 K on the BM1B beamline at the ESRF (Grenoble). The starting model of the structure was found by Monte Carlo simulated annealing. The final structure was obtained through Rietveld refinements performed with soft restraints on interatomic bond lengths and angles. The symmetry is orthorhombic, space groupP21212, with 12 molecules within the cell [a= 24.3012 (2),b= 20.5726 (2),c= 4.8672 (1) Å,V= 2433.30 (3) Å3,Z′ = 3, 36 non-H independent atoms]. Crystalline cohesion between neighbouring molecules is achieved by three networks of O—H...O hydrogen bonds. The width of the Bragg peaks is interpreted through a microstructural approach in terms of anisotropic strain effects.
Lattice strain effects in the measurement of the Si lattice parameter by Laue-case double-crystal diffractometry
Authors: Mana Giovanni , Palmisano Carlo , Zosi Gianfranco
Published: September 2004

The measurement of the (220) Bragg-plane spacing of Si by Laue-case double-crystal diffractometry with an uncertainty lower than 10−8requires a detailed theoretical framework that includes the study of lattice strain. In the present paper, the propagation of X-rays through a deformed crystal is re-examined and the influence of a constant strain gradient on the centre of the reflection domain is studied by means of Takagi's equations. Their analytical and numerical solutions indicate that the measured lattice spacing refers to the crystal entrance surface.