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  1. Combining Affymetrix microarray results

    Directory of Open Access Journals (Sweden)

    Doerge RW

    2005-03-01

    Full Text Available Abstract Background As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis. Results We propose a statistically-based meta-analytic approach to microarray analysis for the purpose of systematically combining results from the different laboratories. This approach provides a more precise view of genes that are significantly related to the condition of interest while simultaneously allowing for differences between laboratories. Of particular interest is the widely used Affymetrix oligonucleotide array, the results of which are naturally suited to a meta-analysis. A simulation model based on the Affymetrix platform is developed to examine the adaptive nature of the meta-analytic approach and to illustrate the usefulness of such an approach in combining microarray results across laboratories. The approach is then applied to real data involving a mouse model for multiple sclerosis. Conclusion The quantitative estimates from the meta-analysis model tend to be closer to the "true" degree of differential expression than any single lab. Meta-analytic methods can systematically combine Affymetrix results from different laboratories to gain a clearer understanding of genes' relationships to specific conditions of interest.

  2. Genotyping and annotation of Affymetrix SNP arrays

    DEFF Research Database (Denmark)

    Lamy, Philippe; Andersen, Claus Lindbjerg; Wikman, Friedrik;

    2006-01-01

    In this paper we develop a new method for genotyping Affymetrix single nucleotide polymorphism (SNP) array. The method is based on (i) using multiple arrays at the same time to determine the genotypes and (ii) a model that relates intensities of individual SNPs to each other. The latter point...... allows us to annotate SNPs that have poor performance, either because of poor experimental conditions or because for one of the alleles the probes do not behave in a dose-response manner. Generally, our method agrees well with a method developed by Affymetrix. When both methods make a call they agree in...... 99.25% (using standard settings) of the cases, using a sample of 113 Affymetrix 10k SNP arrays. In the majority of cases where the two methods disagree, our method makes a genotype call, whereas the method by Affymetrix makes a no call, i.e. the genotype of the SNP is not determined. By visualization...

  3. One-cycle control of switching converters

    OpenAIRE

    Smedley, Keyue M.; Ćuk, Slobodan

    1995-01-01

    A new large-signal nonlinear control technique is proposed to control the duty-ratio d of a switch such that in each cycle the average value of a switched variable of the switching converter is exactly equal to or proportional to the control reference in the steady-state or in a transient. One-cycle control rejects power source perturbations in one switching cycle; the average value of the switched variable follows the dynamic reference in one switching cycle; and the controller corrects swit...

  4. Modelling background intensity in Affymetrix Genechips

    CERN Document Server

    Kroll, K M; Carlon, E

    2008-01-01

    DNA microarrays are devices that are able, in principle, to detect and quantify the presence of specific nucleic acid sequences in complex biological mixtures. The measurement consists in detecting fluorescence signals from several spots on the microarray surface onto which different probe sequences are grafted. One of the problems of the data analysis is that the signal contains a noisy background component due to non-specific binding. This paper presents a physical model for background estimation in Affymetrix Genechips. It combines two different approaches. The first is based on the sequence composition, specifically its sequence dependent hybridization affinity. The second is based on the strong correlation of intensities from locations which are the physical neighbors of a specific spot on the chip. Both effects are incorporated in a background functional which contains 24 free parameters, fixed by minimization on a training data set. In all data analyzed the sequence specific parameters, obtained by min...

  5. A new genotype calling method for affymetrix SNP arrays.

    Science.gov (United States)

    Fu, Bilin; Xu, Jin

    2011-12-01

    Current genotype-calling methods such as Robust Linear Model with Mahalanobis Distance Classifier (RLMM) and Corrected Robust Linear Model with Maximum Likelihood Classification (CRLMM) provide accurate calling results for Affymetrix Single Nucleotide Polymorphisms (SNP) chips. However, these methods are computationally expensive as they employ preprocess procedures, including chip data normalization and other sophisticated statistical techniques. In the small sample case the accuracy rate may drop significantly. We develop a new genotype calling method for Affymetrix 100 k and 500 k SNP chips. A two-stage classification scheme is proposed to obtain a fast genotype calling algorithm. The first stage uses unsupervised classification to quickly discriminate genotypes with high accuracy for the majority of the SNPs. And the second stage employs a supervised classification method to incorporate allele frequency information either from the HapMap data or from a self-training scheme. Confidence score is provided for every genotype call. The overall performance is shown to be comparable to that of CRLMM as verified by the known gold standard HapMap data and is superior in small sample cases. The new algorithm is computationally simple and standalone in the sense that a self-training scheme can be used without employing any other training data. A package implementing the calling algorithm is freely available at http://www.sfs.ecnu.edu.cn/teachers/xuj_en.html. PMID:22084010

  6. Computational method for reducing variance with Affymetrix microarrays

    Directory of Open Access Journals (Sweden)

    Brooks Andrew I

    2002-08-01

    Full Text Available Abstract Background Affymetrix microarrays are used by many laboratories to generate gene expression profiles. Generally, only large differences (> 1.7-fold between conditions have been reported. Computational methods to reduce inter-array variability might be of value when attempting to detect smaller differences. We examined whether inter-array variability could be reduced by using data based on the Affymetrix algorithm for pairwise comparisons between arrays (ratio method rather than data based on the algorithm for analysis of individual arrays (signal method. Six HG-U95A arrays that probed mRNA from young (21–31 yr old human muscle were compared with six arrays that probed mRNA from older (62–77 yr old muscle. Results Differences in mean expression levels of young and old subjects were small, rarely > 1.5-fold. The mean within-group coefficient of variation for 4629 mRNAs expressed in muscle was 20% according to the ratio method and 25% according to the signal method. The ratio method yielded more differences according to t-tests (124 vs. 98 differences at P Conclusion The ratio method reduces inter-array variance and thereby enhances statistical power.

  7. DMET-Analyzer: automatic analysis of Affymetrix DMET Data

    Directory of Open Access Journals (Sweden)

    Guzzi Pietro

    2012-10-01

    Full Text Available Abstract Background Clinical Bioinformatics is currently growing and is based on the integration of clinical and omics data aiming at the development of personalized medicine. Thus the introduction of novel technologies able to investigate the relationship among clinical states and biological machineries may help the development of this field. For instance the Affymetrix DMET platform (drug metabolism enzymes and transporters is able to study the relationship among the variation of the genome of patients and drug metabolism, detecting SNPs (Single Nucleotide Polymorphism on genes related to drug metabolism. This may allow for instance to find genetic variants in patients which present different drug responses, in pharmacogenomics and clinical studies. Despite this, there is currently a lack in the development of open-source algorithms and tools for the analysis of DMET data. Existing software tools for DMET data generally allow only the preprocessing of binary data (e.g. the DMET-Console provided by Affymetrix and simple data analysis operations, but do not allow to test the association of the presence of SNPs with the response to drugs. Results We developed DMET-Analyzer a tool for the automatic association analysis among the variation of the patient genomes and the clinical conditions of patients, i.e. the different response to drugs. The proposed system allows: (i to automatize the workflow of analysis of DMET-SNP data avoiding the use of multiple tools; (ii the automatic annotation of DMET-SNP data and the search in existing databases of SNPs (e.g. dbSNP, (iii the association of SNP with pathway through the search in PharmaGKB, a major knowledge base for pharmacogenomic studies. DMET-Analyzer has a simple graphical user interface that allows users (doctors/biologists to upload and analyse DMET files produced by Affymetrix DMET-Console in an interactive way. The effectiveness and easy use of DMET Analyzer is demonstrated through different

  8. A New, Highly Improved Two-Cycle Engine

    Science.gov (United States)

    Wiesen, Bernard

    2008-01-01

    The figure presents a cross-sectional view of a supercharged, variable-compression, two-cycle, internal-combustion engine that offers significant advantages over prior such engines. The improvements are embodied in a combination of design changes that contribute synergistically to improvements in performance and economy. Although the combination of design changes and the principles underlying them are complex, one of the main effects of the changes on the overall engine design is reduced (relative to prior two-cycle designs) mechanical complexity, which translates directly to reduced manufacturing cost and increased reliability. Other benefits include increases in the efficiency of both scavenging and supercharging. The improvements retain the simplicity and other advantages of two-cycle engines while affording increases in volumetric efficiency and performance across a wide range of operating conditions that, heretofore have been accessible to four-cycle engines but not to conventionally scavenged two-cycle ones, thereby increasing the range of usefulness of the two-cycle engine into all areas now dominated by the four-cycle engine. The design changes and benefits are too numerous to describe here in detail, but it is possible to summarize the major improvements: Reciprocating Shuttle Inlet Valve The entire reciprocating shuttle inlet valve and its operating gear is constructed as a single member. The shuttle valve is actuated in a lost-motion arrangement in which, at the ends of its stroke, projections on the shuttle valve come to rest against abutments at the ends of grooves in a piston skirt. This shuttle-valve design obviates the customary complex valve mechanism, actuated from an engine crankshaft or camshaft, yet it is effective with every type of two-cycle engine, from small high-speed single cylinder model engines, to large low-speed multiple cylinder engines.

  9. Software comparison for evaluating genomic copy number variation for Affymetrix 6.0 SNP array platform

    Science.gov (United States)

    2011-01-01

    Background Copy number data are routinely being extracted from genome-wide association study chips using a variety of software. We empirically evaluated and compared four freely-available software packages designed for Affymetrix SNP chips to estimate copy number: Affymetrix Power Tools (APT), Aroma.Affymetrix, PennCNV and CRLMM. Our evaluation used 1,418 GENOA samples that were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0. We compared bias and variance in the locus-level copy number data, the concordance amongst regions of copy number gains/deletions and the false-positive rate amongst deleted segments. Results APT had median locus-level copy numbers closest to a value of two, whereas PennCNV and Aroma.Affymetrix had the smallest variability associated with the median copy number. Of those evaluated, only PennCNV provides copy number specific quality-control metrics and identified 136 poor CNV samples. Regions of copy number variation (CNV) were detected using the hidden Markov models provided within PennCNV and CRLMM/VanillaIce. PennCNV detected more CNVs than CRLMM/VanillaIce; the median number of CNVs detected per sample was 39 and 30, respectively. PennCNV detected most of the regions that CRLMM/VanillaIce did as well as additional CNV regions. The median concordance between PennCNV and CRLMM/VanillaIce was 47.9% for duplications and 51.5% for deletions. The estimated false-positive rate associated with deletions was similar for PennCNV and CRLMM/VanillaIce. Conclusions If the objective is to perform statistical tests on the locus-level copy number data, our empirical results suggest that PennCNV or Aroma.Affymetrix is optimal. If the objective is to perform statistical tests on the summarized segmented data then PennCNV would be preferred over CRLMM/VanillaIce. Specifically, PennCNV allows the analyst to estimate locus-level copy number, perform segmentation and evaluate CNV-specific quality-control metrics within a single software package

  10. Coverage and characteristics of the Affymetrix GeneChip Human Mapping 100K SNP set.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available Improvements in technology have made it possible to conduct genome-wide association mapping at costs within reach of academic investigators, and experiments are currently being conducted with a variety of high-throughput platforms. To provide an appropriate context for interpreting results of such studies, we summarize here results of an investigation of one of the first of these technologies to be publicly available, the Affymetrix GeneChip Human Mapping 100K set of single nucleotide polymorphisms (SNPs. In a systematic analysis of the pattern and distribution of SNPs in the Mapping 100K set, we find that SNPs in this set are undersampled from coding regions (both nonsynonymous and synonymous and oversampled from regions outside genes, relative to SNPs in the overall HapMap database. In addition, we utilize a novel multilocus linkage disequilibrium (LD coefficient based on information content (analogous to the information content scores commonly used for linkage mapping that is equivalent to the familiar measure r2 in the special case of two loci. Using this approach, we are able to summarize for any subset of markers, such as the Affymetrix Mapping 100K set, the information available for association mapping in that subset, relative to the information available in the full set of markers included in the HapMap, and highlight circumstances in which this multilocus measure of LD provides substantial additional insight about the haplotype structure in a region over pairwise measures of LD.

  11. Genome-wide analysis of antisense transcription with Affymetrix exon array

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    Jung Yong-chul

    2008-01-01

    Full Text Available Abstract Background A large number of natural antisense transcripts have been identified in human and mouse genomes. Study of their potential functions clearly requires cost-efficient method for expression analysis. Results Here we show that Affymetrix Exon arrays, which were designed to detect conventional transcripts in the sense orientation, can be used to monitor antisense expression across all exonic loci in mammalian genomes. Through modification of the cDNA synthesis protocol, we labeled single-strand cDNA in the reverse orientation as in the standard protocol, thus enabling the detection of antisense transcripts using the same array. Applying this technique to human Jurkat cells, we identified antisense transcription at 2,088 exonic loci of 1,516 UniGene clusters. Many of these antisense transcripts were not observed previously and some were validated by orientation-specific RT-PCR. Conclusion Our results suggest that with a modified protocol Affymetrix human, mouse and rat Exon arrays can be used as a routine method for genome-wide analysis of antisense transcription in these genomes.

  12. μ-CS: An extension of the TM4 platform to manage Affymetrix binary data

    Directory of Open Access Journals (Sweden)

    Cannataro Mario

    2010-06-01

    Full Text Available Abstract Background A main goal in understanding cell mechanisms is to explain the relationship among genes and related molecular processes through the combined use of technological platforms and bioinformatics analysis. High throughput platforms, such as microarrays, enable the investigation of the whole genome in a single experiment. There exist different kind of microarray platforms, that produce different types of binary data (images and raw data. Moreover, also considering a single vendor, different chips are available. The analysis of microarray data requires an initial preprocessing phase (i.e. normalization and summarization of raw data that makes them suitable for use on existing platforms, such as the TIGR M4 Suite. Nevertheless, the annotations of data with additional information such as gene function, is needed to perform more powerful analysis. Raw data preprocessing and annotation is often performed in a manual and error prone way. Moreover, many available preprocessing tools do not support annotation. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of microarray data are needed. Results The paper presents μ-CS (Microarray Cel file Summarizer, a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix binary data. μ-CS is based on a client-server architecture. The μ-CS client is provided both as a plug-in of the TIGR M4 platform and as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data, avoiding the manual invocation of external tools (e.g. the Affymetrix Power Tools, the manual loading of preprocessing libraries, and the management of intermediate files. The μ-CS server automatically updates the references to the summarization and annotation libraries that are provided to the μ-CS client before the preprocessing. The μ-CS server is based on the web services technology

  13. Exon array data analysis using Affymetrix power tools and R statistical software

    Science.gov (United States)

    2011-01-01

    The use of microarray technology to measure gene expression on a genome-wide scale has been well established for more than a decade. Methods to process and analyse the vast quantity of expression data generated by a typical microarray experiment are similarly well-established. The Affymetrix Exon 1.0 ST array is a relatively new type of array, which has the capability to assess expression at the individual exon level. This allows a more comprehensive analysis of the transcriptome, and in particular enables the study of alternative splicing, a gene regulation mechanism important in both normal conditions and in diseases. Some aspects of exon array data analysis are shared with those for standard gene expression data but others present new challenges that have required development of novel tools. Here, I will introduce the exon array and present a detailed example tutorial for analysis of data generated using this platform. PMID:21498550

  14. ArrayInitiative - a tool that simplifies creating custom Affymetrix CDFs

    Directory of Open Access Journals (Sweden)

    Thompson Kevin J

    2011-05-01

    Full Text Available Abstract Background Probes on a microarray represent a frozen view of a genome and are quickly outdated when new sequencing studies extend our knowledge, resulting in significant measurement error when analyzing any microarray experiment. There are several bioinformatics approaches to improve probe assignments, but without in-house programming expertise, standardizing these custom array specifications as a usable file (e.g. as Affymetrix CDFs is difficult, owing mostly to the complexity of the specification file format. However, without correctly standardized files there is a significant barrier for testing competing analysis approaches since this file is one of the required inputs for many commonly used algorithms. The need to test combinations of probe assignments and analysis algorithms led us to develop ArrayInitiative, a tool for creating and managing custom array specifications. Results ArrayInitiative is a standalone, cross-platform, rich client desktop application for creating correctly formatted, custom versions of manufacturer-provided (default array specifications, requiring only minimal knowledge of the array specification rules and file formats. Users can import default array specifications, import probe sequences for a default array specification, design and import a custom array specification, export any array specification to multiple output formats, export the probe sequences for any array specification and browse high-level information about the microarray, such as version and number of probes. The initial release of ArrayInitiative supports the Affymetrix 3' IVT expression arrays we currently analyze, but as an open source application, we hope that others will contribute modules for other platforms. Conclusions ArrayInitiative allows researchers to create new array specifications, in a standard format, based upon their own requirements. This makes it easier to test competing design and analysis strategies that depend on probe

  15. Discovery and mapping of single feature polymorphisms in wheat using Affymetrix arrays

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    Hu Shengwa

    2009-05-01

    Full Text Available Abstract Background Wheat (Triticum aestivum L. is a staple food crop worldwide. The wheat genome has not yet been sequenced due to its huge genome size (~17,000 Mb and high levels of repetitive sequences; the whole genome sequence may not be expected in the near future. Available linkage maps have low marker density due to limitation in available markers; therefore new technologies that detect genome-wide polymorphisms are still needed to discover a large number of new markers for construction of high-resolution maps. A high-resolution map is a critical tool for gene isolation, molecular breeding and genomic research. Single feature polymorphism (SFP is a new microarray-based type of marker that is detected by hybridization of DNA or cRNA to oligonucleotide probes. This study was conducted to explore the feasibility of using the Affymetrix GeneChip to discover and map SFPs in the large hexaploid wheat genome. Results Six wheat varieties of diverse origins (Ning 7840, Clark, Jagger, Encruzilhada, Chinese Spring, and Opata 85 were analyzed for significant probe by variety interactions and 396 probe sets with SFPs were identified. A subset of 164 unigenes was sequenced and 54% showed polymorphism within probes. Microarray analysis of 71 recombinant inbred lines from the cross Ning 7840/Clark identified 955 SFPs and 877 of them were mapped together with 269 simple sequence repeat markers. The SFPs were randomly distributed within a chromosome but were unevenly distributed among different genomes. The B genome had the most SFPs, and the D genome had the least. Map positions of a selected set of SFPs were validated by mapping single nucleotide polymorphism using SNaPshot and comparing with expressed sequence tags mapping data. Conclusion The Affymetrix array is a cost-effective platform for SFP discovery and SFP mapping in wheat. The new high-density map constructed in this study will be a useful tool for genetic and genomic research in wheat.

  16. OpenADAM: an open source genome-wide association data management system for Affymetrix SNP arrays

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    Sham P C

    2008-12-01

    Full Text Available Abstract Background Large scale genome-wide association studies have become popular since the introduction of high throughput genotyping platforms. Efficient management of the vast array of data generated poses many challenges. Description We have developed an open source web-based data management system for the large amount of genotype data generated from the Affymetrix GeneChip® Mapping Array and Affymetrix Genome-Wide Human SNP Array platforms. The database supports genotype calling using DM, BRLMM, BRLMM-P or Birdseed algorithms provided by the Affymetrix Power Tools. The genotype and corresponding pedigree data are stored in a relational database for efficient downstream data manipulation and analysis, such as calculation of allele and genotype frequencies, sample identity checking, and export of genotype data in various file formats for analysis using commonly-available software. A novel method for genotyping error estimation is implemented using linkage disequilibrium information from the HapMap project. All functionalities are accessible via a web-based user interface. Conclusion OpenADAM provides an open source database system for management of Affymetrix genome-wide association SNP data.

  17. A Scaling Law of Photoelectron Angular Distributions in One-Cycle Laser Pulses

    Institute of Scientific and Technical Information of China (English)

    BAI Li-Hua; ZHANG Jing-Tao; XU Zhi-Zhan

    2005-01-01

    @@ The photoelectron angular distributions (PADs) from above-threshold ionization of atoms irradiated by one-cycle laser pulses satisfy a scaling law.The scaling law denotes that the main features of the PADs are determined by four dimensionless parameters: (1) the ponderomotive number up = Up/hω, the ponderomotive energy Up in units of laser photon energy; (2) the binding number εb = Eb/hω, the atomic binding energy Eb in units of laser photon energy; (3) the number of absorbed photons q; (4) the carrier-envelope phase Φ0, the phase of the carrier wave with respect to the envelope.We verify the scaling law by theoretical analysis and numerical calculation,compared to that in long-pulse case.A possible experimental test to verify the scaling law is suggested.

  18. The Affymetrix DMET Plus Platform Reveals Unique Distribution of ADME-Related Variants in Ethnic Arabs

    Directory of Open Access Journals (Sweden)

    Salma M. Wakil

    2015-01-01

    Full Text Available Background. The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET Plus Premier Pack has been designed to genotype 1936 gene variants thought to be essential for screening patients in personalized drug therapy. These variants include the cytochrome P450s (CYP450s, the key metabolizing enzymes, many other enzymes involved in phase I and phase II pharmacokinetic reactions, and signaling mediators associated with variability in clinical response to numerous drugs not only among individuals, but also between ethnic populations. Materials and Methods. We genotyped 600 Saudi individuals for 1936 variants on the DMET platform to evaluate their clinical potential in personalized medicine in ethnic Arabs. Results. Approximately 49% each of the 437 CYP450 variants, 56% of the 581 transporters, 56% of 419 transferases, 48% of the 104 dehydrogenases, and 58% of the remaining 390 variants were detected. Several variants, such as rs3740071, rs6193, rs258751, rs6199, rs11568421, and rs8187797, exhibited significantly either higher or lower minor allele frequencies (MAFs than those in other ethnic groups. Discussion. The present study revealed some unique distribution trends for several variants in Arabs, which displayed partly inverse allelic prevalence compared to other ethnic populations. The results point therefore to the need to verify and ascertain the prevalence of a variant as a prerequisite for engaging it in clinical routine screening in personalized medicine in any given population.

  19. A Bayesian calibration model for combining different pre-processing methods in Affymetrix chips

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    Richardson Sylvia

    2008-12-01

    Full Text Available Abstract Background In gene expression studies a key role is played by the so called "pre-processing", a series of steps designed to extract the signal and account for the sources of variability due to the technology used rather than to biological differences between the RNA samples. At the moment there is no commonly agreed gold standard pre-processing method and each researcher has the responsibility to choose one method, incurring the risk of false positive and false negative features arising from the particular method chosen. Results We propose a Bayesian calibration model that makes use of the information provided by several pre-processing methods and we show that this model gives a better assessment of the 'true' unknown differential expression between two conditions. We demonstrate how to estimate the posterior distribution of the differential expression values of interest from the combined information. Conclusion On simulated data and on the spike-in Latin Square dataset from Affymetrix the Bayesian calibration model proves to have more power than each pre-processing method. Its biological interest is demonstrated through an experimental example on publicly available data.

  20. Investigation after one cycle on Doel 3 tubes sleeved by Westinghouse

    International Nuclear Information System (INIS)

    At DOEL 3, 55 SG-tubes cracked at the roll transition area were repaired by Westinghouse in 1988 by CO2 laser welded sleeving, with a post weld stress relief. After one cycle two sleeved tubes were pulled out for investigation. The main purpose of this investigation was the correlation with the on-site UT-inspection, performed after sleeving, because surface irregularities of the weld had disturbed the determination of the weld penetration for several tubes. A good correlation between the UT-results and the direct examination is found for the two tubes which are both affected by surface irregularities on the majority of the circumference. Another important goal of the investigation is the verification of the resistance to primary water stress corrosion cracking of the upper joint of the sleeve, namely at the upper transition area and near the weld because the parent tube is very susceptible to this corrosion and because residual stresses could remain after the complete sleeving process. After one year no tube nor sleeve degradation could be observed so that it was decided to maintain the remaining sleeved tubes in service

  1. Investigation after one cycle on DOEL 3 tubes sleeved by Westinghouse

    International Nuclear Information System (INIS)

    At DOEL 3, 55 steam generator tubes cracked at the roll transition were repaired by Westinghouse in 1988 by CO2 laser welded sleeving, with post weld stress relieving. After one cycle, two sleeved tubes were pulled out for examination. The main purpose of this examination was the correlation with the on-site ultrasonic inspection performed after sleeving, because surface irregularities of the weld had interfered with the determination of weld penetration in the case of several sleeves. Good correlation between the ultrasonic results and the direct examination was found for the two tubes, which are both affected by surface irregularities on the majority of the circumference. Another important goal of the examination is the verification of the resistance to primary water stress corrosion cracking of the upper joint of the sleeve. After one year's service, no degradation was observed so that it was decided to keep all the other sleeves in service. This examination also shows the differences between the pulled-out tubes and the laboratory models examined beforehand, which highlights the problem of the reproducibility of such a process. (author)

  2. High Fidelity Copy Number Analysis of Formalin-Fixed and Paraffin-Embedded Tissues Using Affymetrix Cytoscan HD Chip

    OpenAIRE

    Yu, Yan P.; Amantha Michalopoulos; Ying Ding; George Tseng; Jian-Hua Luo

    2014-01-01

    Detection of human genome copy number variation (CNV) is one of the most important analyses in diagnosing human malignancies. Genome CNV detection in formalin-fixed and paraffin-embedded (FFPE) tissues remains challenging due to suboptimal DNA quality and failure to use appropriate baseline controls for such tissues. Here, we report a modified method in analyzing CNV in FFPE tissues using microarray with Affymetrix Cytoscan HD chips. Gel purification was applied to select DNA with good qualit...

  3. ‘maskBAD’ – a package to detect and remove Affymetrix probes with binding affinity differences

    Directory of Open Access Journals (Sweden)

    Dannemann Michael

    2012-04-01

    Full Text Available Abstract Background Hybridization differences caused by target sequence differences can be a confounding factor in analyzing gene expression on microarrays, lead to false positives and reduce power to detect real expression differences. We prepared an R Bioconductor compatible package to detect, characterize and remove such probes in Affymetrix 3’IVT and exon-based arrays on the basis of correlation of signal intensities from probes within probe sets. Results Using completely mouse genomes we determined type 1 (false negatives and type 2 (false positives errors with high accuracy and we show that our method routinely outperforms previous methods. When detecting 76.2% of known SNP/indels in mouse expression data, we obtain at most 5.5% false positives. At the same level of false positives, best previous method detected 72.6%. We also show that probes with differing binding affinity both hinder differential expression detection and introduce artifacts in cancer-healthy tissue comparison. Conclusions Detection and removal of such probes should be a routine step in Affymetrix data preprocessing. We prepared a user friendly R package, compatible with Bioconductor, that allows the filtering and improving of data from Affymetrix microarrays experiments.

  4. Ranking differentially expressed genes from Affymetrix gene expression data: methods with reproducibility, sensitivity, and specificity

    Directory of Open Access Journals (Sweden)

    Shimizu Kentaro

    2009-04-01

    Full Text Available Abstract Background To identify differentially expressed genes (DEGs from microarray data, users of the Affymetrix GeneChip system need to select both a preprocessing algorithm to obtain expression-level measurements and a way of ranking genes to obtain the most plausible candidates. We recently recommended suitable combinations of a preprocessing algorithm and gene ranking method that can be used to identify DEGs with a higher level of sensitivity and specificity. However, in addition to these recommendations, researchers also want to know which combinations enhance reproducibility. Results We compared eight conventional methods for ranking genes: weighted average difference (WAD, average difference (AD, fold change (FC, rank products (RP, moderated t statistic (modT, significance analysis of microarrays (samT, shrinkage t statistic (shrinkT, and intensity-based moderated t statistic (ibmT with six preprocessing algorithms (PLIER, VSN, FARMS, multi-mgMOS (mmgMOS, MBEI, and GCRMA. A total of 36 real experimental datasets was evaluated on the basis of the area under the receiver operating characteristic curve (AUC as a measure for both sensitivity and specificity. We found that the RP method performed well for VSN-, FARMS-, MBEI-, and GCRMA-preprocessed data, and the WAD method performed well for mmgMOS-preprocessed data. Our analysis of the MicroArray Quality Control (MAQC project's datasets showed that the FC-based gene ranking methods (WAD, AD, FC, and RP had a higher level of reproducibility: The percentages of overlapping genes (POGs across different sites for the FC-based methods were higher overall than those for the t-statistic-based methods (modT, samT, shrinkT, and ibmT. In particular, POG values for WAD were the highest overall among the FC-based methods irrespective of the choice of preprocessing algorithm. Conclusion Our results demonstrate that to increase sensitivity, specificity, and reproducibility in microarray analyses, we need

  5. In Vivo Treatment Sensitivity Testing With Positron Emission Tomography/Computed Tomography After One Cycle of Chemotherapy for Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin; Kostakoglu, Lale; Zaucha, Jan Maciej;

    2014-01-01

    PURPOSE: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding...

  6. Dissecting an alternative splicing analysis workflow for GeneChip® Exon 1.0 ST Affymetrix arrays

    Directory of Open Access Journals (Sweden)

    Calogero Raffaele A

    2008-11-01

    Full Text Available Abstract Background A new microarray platform (GeneChip® Exon 1.0 ST has recently been developed by Affymetrix http://www.affymetrix.com. This microarray platform changes the conventional view of transcript analysis since it allows the evaluation of the expression level of a transcript by querying each exon component. The Exon 1.0 ST platform does however raise some issues regarding the approaches to be used in identifying genome-wide alternative splicing events (ASEs. In this study an exon-level data analysis workflow is dissected in order to detect limit and strength of each step, thus modifying the overall workflow and thereby optimizing the detection of ASEs. Results This study was carried out using a semi-synthetic exon-skipping benchmark experiment embedding a total of 268 exon skipping events. Our results point out that summarization methods (RMA, PLIER do not affect the efficacy of statistical tools in detecting ASEs. However, data pre-filtering is mandatory if the detected number of false ASEs are to be reduced. MiDAS and Rank Product methods efficiently detect true ASEs but they suffer from the lack of multiple test error correction. The intersection of MiDAS and Rank Product results efficiently moderates the detection of false ASEs. Conclusion To optimize the detection of ASEs we propose the following workflow: i data pre-filtering, ii statistical selection of ASEs using both MiDAS and Rank Product, iii intersection of results derived from the two statistical analyses in order to moderate family-wise errors (FWER.

  7. PERFORMANCE OF A TWO-CYCLE REFRIGERATOR/FREEZER USING HFC REFRIGERANTS

    Science.gov (United States)

    A two-cycle 18 ft3 (0.51 m3) refrigerator/freezer (R/F) was tested utilizing American National Standards Institute (ANSI)/AHAM (1988) standards for energy consumption testing. A 34.9% energy consumption reduction was realized. This work presents a proven method of reducing the ...

  8. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  9. Asymmetry of the photoionization rate of H atoms by a sequence of one-cycle laser pulses

    Institute of Scientific and Technical Information of China (English)

    Bai Li-Hua; Zhang Jing-Tao; Xu Zhi-Zhan

    2005-01-01

    Using an unperturbed scattering theory, the characteristics of H atom photoionization are studied respectively by a linearly- and by a circularly- polarized one-cycle laser pulse sequence. The asymmetry for photoelectrons in two directions opposite to each other is investigated. It is found that the asymmetry degree varies with the carrier-envelope (CE) phase, laser intensity, as well as the kinetic energy of photoelectrons. For the linear polarization, the maximal ionization rate varies with the CE phase, and the asymmetry degree varies with the CE phase in a sine-like pattern.For the circular polarization, the maximal ionization rate keeps constant for various CE phases, but the variation of asymmetry degree is still in a sine-like pattern.

  10. A high-resolution and one-cycle conversion time-to-digital converter architecture for PET image applications.

    Science.gov (United States)

    Sheng, Duo; Chung, Ching-Che; Huang, Chih-Chung; Jian, Jia-Wei

    2013-01-01

    In this paper, a high-resolution and one-cycle conversion time-to-digital converter (TDC) architecture with cell-based design for positron emission tomography (PET) applications is presented. The proposed TDC employs a cascade-stage structure to achieve high timing resolution and wide sampling range at the same time. Besides, based on the proposed two-level conversion structure, the proposed TDC not only can achieve single cycle latency and high speed of operation, but also have low circuit complexity as compared with conventional approaches. Simulation results show that operation frequency of the proposed TDC can be improved to 200 MHz with 50 ps resolution. In addition, the proposed TDC can be implemented with standard cells, making it easily portable to different processes and very suitable for biomedical chip applications. PMID:24110225

  11. One-Cycle Control Approach for Flyback Inverter%单周控制反激逆变器

    Institute of Scientific and Technical Information of China (English)

    蔡可健; 张颖; 程晓燕

    2011-01-01

    研究了一种单周控制高频链反激DC-AC变换器,该逆变器由高频变换器、周波变换器及高频储能变压器构成。通过有序地控制各开关管的通断,实现了正弦交流电的输出。对基于工作在电感电流连续模式的反激逆变器,在同步整流的基础上提出了单周控制策略,提高了逆变器的控制精度和响应速度,增强了抑制扰动的能力。最后详细介绍了电路的工作原理和控制原理,通过实验验证了理论的正确性,证明了电路的可行性。%A novel one-cycle control high frequency link flyback DC-AC converter is presented,which inverter consist of high frequency converter,cycloconverter and high frequency energy storage transformer.By controlling each power FET in order,it could output a sinusoidal alternating current.One-cycle control strategy is established on flyback inverter which working under the inductor current continuous conduction mode,and based on synchronous rectification,which improves the control precision and response speed,and enhances the ability to suppress disturbances.The working principle and circuit control principle are described in detail.Experimental results show the correctness of the theory to prove the feasibility of the circuit.

  12. Comparison of seven methods for producing Affymetrix expression scores based on False Discovery Rates in disease profiling data

    Directory of Open Access Journals (Sweden)

    Gruber Stephen B

    2005-02-01

    given greater consideration when comparing Affymetrix processing methods.

  13. Addenda/Corrigenda: Fixed Points and Two-cycles of the Discrete Logarithm

    OpenAIRE

    Holden, Joshua

    2002-01-01

    The abstract of the original paper was as follows: We explore some questions related to one of Brizolis: does every prime p have a pair (g,h) such that h is a fixed point for the discrete logarithm with base g? We extend this question to ask about not only fixed points but also two-cycles. Campbell and Pomerance have not only answered the fixed point question for sufficiently large p but have also rigorously estimated the number of such pairs given certain conditions on g and h. We attempt to...

  14. Nonlinear optics with phase-controlled pulses in the sub-two-cycle regime.

    Science.gov (United States)

    Morgner, U; Ell, R; Metzler, G; Schibli, T R; Kärtner, F X; Fujimoto, J G; Haus, H A; Ippen, E P

    2001-06-11

    Nonlinear optical effects due to the phase between carrier and envelope are observed with 5 fs pulses from a Kerr-lens mode-locked Ti:sapphire laser. These sub-two-cycle pulses with octave spanning spectra are the shortest pulses ever generated directly from a laser oscillator. Detection of the carrier-envelope phase slip is made possible by simply focusing the short pulses directly from the oscillator into a BBO crystal. As a further example of nonlinear optics with such short pulses, the interference between second- and third-harmonic components is also demonstrated. PMID:11415276

  15. Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

    OpenAIRE

    Van Laere, S; Van der Auwera, I; Van den Eynden, G; Van Hummelen, P; van Dam, P; Van Marck, E; Vermeulen, P B; Dirix, L

    2007-01-01

    The present study aims at a platform-independent confirmation of previously obtained cDNA microarray results on inflammatory breast cancer (IBC) using Affymetrix chips. Gene-expression data of 19 IBC and 40 non-IBC specimens were subjected to clustering and principal component analysis. The performance of a previously identified IBC signature was tested using clustering and gene set enrichment analysis. The presence of different cell-of-origin subtypes in IBC was investigated and confirmed us...

  16. Large-scale analysis of antisense transcription in wheat using the Affymetrix GeneChip Wheat Genome Array

    Directory of Open Access Journals (Sweden)

    Settles Matthew L

    2009-05-01

    Full Text Available Abstract Background Natural antisense transcripts (NATs are transcripts of the opposite DNA strand to the sense-strand either at the same locus (cis-encoded or a different locus (trans-encoded. They can affect gene expression at multiple stages including transcription, RNA processing and transport, and translation. NATs give rise to sense-antisense transcript pairs and the number of these identified has escalated greatly with the availability of DNA sequencing resources and public databases. Traditionally, NATs were identified by the alignment of full-length cDNAs or expressed sequence tags to genome sequences, but an alternative method for large-scale detection of sense-antisense transcript pairs involves the use of microarrays. In this study we developed a novel protocol to assay sense- and antisense-strand transcription on the 55 K Affymetrix GeneChip Wheat Genome Array, which is a 3' in vitro transcription (3'IVT expression array. We selected five different tissue types for assay to enable maximum discovery, and used the 'Chinese Spring' wheat genotype because most of the wheat GeneChip probe sequences were based on its genomic sequence. This study is the first report of using a 3'IVT expression array to discover the expression of natural sense-antisense transcript pairs, and may be considered as proof-of-concept. Results By using alternative target preparation schemes, both the sense- and antisense-strand derived transcripts were labeled and hybridized to the Wheat GeneChip. Quality assurance verified that successful hybridization did occur in the antisense-strand assay. A stringent threshold for positive hybridization was applied, which resulted in the identification of 110 sense-antisense transcript pairs, as well as 80 potentially antisense-specific transcripts. Strand-specific RT-PCR validated the microarray observations, and showed that antisense transcription is likely to be tissue specific. For the annotated sense

  17. A new high-performance AC/DC power factor correction switching converter based on one-cycle control technology and active floating-charge technology

    Institute of Scientific and Technical Information of China (English)

    GAO Chao

    2008-01-01

    A new family of converters, high-performance AC/DC power factor correction (PFC) switching converters with one-cycle control technology and active floating-charge technology, was derived and experimentally verified. The topology of a single-phase CCM and DCM Boost-PFC switching converter was also analyzed. Its operating prniciples and control methods were expounded. Based on these, a new type of AC/DC switching converter circuits for PFC combined with one-cycle control technology was presented herein. The proposed AC/DC switching converter significantly helps improve the converter efficiency and its power factor value.

  18. Supercharged two-cycle engines employing novel single element reciprocating shuttle inlet valve mechanisms and with a variable compression ratio

    Science.gov (United States)

    Wiesen, Bernard (Inventor)

    2008-01-01

    This invention relates to novel reciprocating shuttle inlet valves, effective with every type of two-cycle engine, from small high-speed single cylinder model engines, to large low-speed multiple cylinder engines, employing spark or compression ignition. Also permitting the elimination of out-of-phase piston arrangements to control scavenging and supercharging of opposed-piston engines. The reciprocating shuttle inlet valve (32) and its operating mechanism (34) is constructed as a single and simple uncomplicated member, in combination with the lost-motion abutments, (46) and (48), formed in a piston skirt, obviating the need for any complex mechanisms or auxiliary drives, unaffected by heat, friction, wear or inertial forces. The reciprocating shuttle inlet valve retains the simplicity and advantages of two-cycle engines, while permitting an increase in volumetric efficiency and performance, thereby increasing the range of usefulness of two-cycle engines into many areas that are now dominated by the four-cycle engine.

  19. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin; Loft, Annika; Hansen, Mads;

    2005-01-01

    Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS......) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had...... negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET-positive patients progressed and 2 died. Three of 61 FDG-PET-negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P...

  20. Simulation Research on Three-Phase PFC Based on One-Cycle-Control%基于单周控制的三相PFC的仿真研究

    Institute of Scientific and Technical Information of China (English)

    戴珂; 彭繁; 张树全; 刘聪

    2011-01-01

    A kind of three-phase PFC circuit wok in CCM mode is introduced. One-cycle-control is applied to achieve unity power factor in three-phase rectifier. This one-cycle control circuit is simple. The core device consists of only one integrator which can be reset, a comparator and a RS flip-flops without any multiplier. This control circuit has advantages of fast response, constant frequency, simple control and so on. Simulation result validates the theoretic analysis finally.%介绍了一种CCM模式下的三相PFC电路,并采用单周控制实现了三相整流器的功率因数校正。单周控制电路的结构十分简单,核心器件仅由一可复位积分器、一比较器和一RS触发器组成,不需要乘法器,从而简化了系统,具有反应快、开关频率恒定、控制方法简单等优点。仿真结果验证了理论分析的正确性。

  1. A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma

    International Nuclear Information System (INIS)

    Neoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC. Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 b.i.d. d1–5 weekly). One cycle of capecitabine (1000 mg/m2 b.i.d. d1–14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation. Between October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2–3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3–4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1–2. Our study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical

  2. Two-cycle curriculum - bachelor-master structure according to the Bologna agreement: the Swiss experience in Basle [

    Directory of Open Access Journals (Sweden)

    Kiessling, Claudia

    2010-04-01

    Full Text Available [english] In the autumn of 2006, the first cohort of students started with the bachelor programme in Basle. The whole curriculum had to be changed from the old system to the new two-cycle system. The implementation of the Bologna reform in Switzerland has been successful especially with regard to the very tight time schedule. Ongoing evaluation will detect fields for improvement which will of course arise in such a fundamental process of change. A major challenge for the future will be the sustainable consolidation of high quality in medical education.

  3. Sperm parameters in rats after low-dose irradiation of sex cells in male parents during two cycles of gametogenesis

    International Nuclear Information System (INIS)

    Chronic combined (internal and external) irradiation in low doses (absorbed doses 0.4 - 3.6 cGy) during two cycles of gametogenesis results in defective stimulation of spermatogenesis in male rats and provokes genotoxic action. The offspring from fathers with 0.7 and 3.6 cGy irradiation have decreased viability and oligozoospermia in mature age. The offsprings from the father with 3.6 cGy have increased sensitivity to weak irradiation and react by increases oligozoospermia. The data are accord with the idea about more pronounced genetic radioresistance of premeiosis cells during gametogenesis

  4. High-power sub-two-cycle mid-infrared pulses at 100 MHz repetition rate

    OpenAIRE

    I. Pupeza; D. Sánchez; Zhang, J.; Lilienfein, N.; Seidel, M.; Karpowicz, N.; Paasch-Colberg, T.; Znakovskaya, I; Pescher, M.; W. Schweinberger; Pervak, V.; Fill, E.; Pronin, O.; Wei, Z.; Krausz, F.

    2015-01-01

    Powerful coherent light with a spectrum spanning the mid-infrared (MIR) spectral range is crucial for a number of applications in natural as well as life sciences, but so far has only been available from large-scale synchrotron sources1. Here we present a compact apparatus that generates pulses with a sub-two-cycle duration and with an average power of 0.1 W and a spectral coverage of 6.8–16.4 μm (at −30 dB). The demonstrated source combines, for the first time in this spectral region, a high...

  5. Comparative Transcriptomic Profiling of Vitis vinifera Under High Light Using a Custom-Made Array and the Affymetrix GeneChip

    Institute of Scientific and Technical Information of China (English)

    Luisa C. Carvalho; Belmiro J. Vilela; Phil M. Mullineaux; Sara Am(a)ncio

    2011-01-01

    Understanding abiotic stress responses is one of the most important issues in plant research nowadays.Abiotic stress,including excess light,can promote the onset of oxidative stress through the accumulation of reactive oxygen species.Oxidative stress also arises when in vitro propagated plants are exposed to high light upon transfer to ex vitro.To determine whether the underlying pathways activated at the transfer of in vitro grapevine to ex vitro conditions reflect the processes occurring upon light stress,we used Vitis vinifera Affymetrix GeneChip (VvGA) and a custom array of genes responsive to light stress (LSCA) detected by real-time reverse transcriptase PCR (qRT-PCR).When gene-expression profiles were compared,‘protein metabolism and modification',‘signaling',and ‘anti-oxidative' genes were more represented in LSCA,while,in VvGA,‘cell wall metabolism' and ‘secondary metabolism' were the categories in which gene expression varied more significantly.The above functional categories confirm previous studies involving other types of abiotic stresses,enhancing the common attributes of abiotic stress defense pathways.The LSCA analysis of our experimental system detected strong response of heat shock genes,particularly the protein rescuing mechanism involving the cooperation of two ATP-dependent chaperone systems,Hsp100 and Hsp70,which showed an unusually late response during the recovery period,of extreme relevance to remove non-functional,potentially harmful polypeptides arising from misfolding,denaturation,or aggregation brought about by stress.The success of LSCA also proves the feasibility of a custommade qRT-PCR approach,particularly for species for which no GeneChip is available and for researchers dealing with a specific and focused problem.

  6. Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

    Directory of Open Access Journals (Sweden)

    Meißner Tobias

    2010-05-01

    Full Text Available Abstract Background Multiple myeloma (MM is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC. In the past few years, many myeloma growth factors (MGF have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them. Methods We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts. Results 4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC and BM plasma cell (BMPC compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC. Conclusions Two major messages arise from this analysis 1 The majority of MGF genes is expressed by the bone marrow environment. 2 Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.

  7. Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

    International Nuclear Information System (INIS)

    Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them. We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts). 4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC. Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM

  8. Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.

    Directory of Open Access Journals (Sweden)

    Stoffel Kevin

    2012-05-01

    Full Text Available Abstract Background High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa. Results We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis. Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and

  9. High-power sub-two-cycle mid-infrared pulses at 100 MHz repetition rate

    Science.gov (United States)

    Pupeza, I.; Sánchez, D.; Zhang, J.; Lilienfein, N.; Seidel, M.; Karpowicz, N.; Paasch-Colberg, T.; Znakovskaya, I.; Pescher, M.; Schweinberger, W.; Pervak, V.; Fill, E.; Pronin, O.; Wei, Z.; Krausz, F.; Apolonski, A.; Biegert, J.

    2015-11-01

    Powerful coherent light with a spectrum spanning the mid-infrared (MIR) spectral range is crucial for a number of applications in natural as well as life sciences, but so far has only been available from large-scale synchrotron sources. Here we present a compact apparatus that generates pulses with a sub-two-cycle duration and with an average power of 0.1 W and a spectral coverage of 6.8-16.4 μm (at -30 dB). The demonstrated source combines, for the first time in this spectral region, a high power, a high repetition rate and phase coherence. The MIR pulses emerge via difference-frequency generation (DFG) driven by the nonlinearly compressed pulses of a Kerr-lens mode-locked ytterbium-doped yttrium-aluminium-garnet (Yb:YAG) thin-disc oscillator. The resultant 100 MHz MIR pulse train is hundreds to thousands of times more powerful than state-of-the-art frequency combs that emit in this range, and offers a high dynamic range for spectroscopy in the molecular fingerprint region and an ideal prerequisite for hyperspectral imaging as well as for the time-domain coherent control of vibrational dynamics.

  10. Genome-Wide analysis of allelic imbalance in laser microdissected prostate cancer tissue using the Affymetrix 50K Mapping array identifies genomic patterns associated with metastasis and differentiation

    DEFF Research Database (Denmark)

    Tørring, Niels; Borre, Michael; Sørensen, Karina;

    2007-01-01

    to be developed for patient stratification based on risk of progression. We analysed laser-microdissected prostate tumour tissue from 43 patients with histologically verified PCa, using the new high-resolution Affymetrix Mapping 50K single-nucleotide polymorphism array. The results showed six major...... loss. However, tumour progression towards a metastatic stage, as well as poor differentiation, was identified by specific patterns of copy number gains of genomic regions located at chromosomes 8q, 1q, 3q and 7q. Androgen ablation therapy was further characterised by copy gain at chromosomes 2p and 10q...

  11. Research on One-Cycle Control Strategy of Matrix Rectifier%矩阵整流器单周期控制策略的研究

    Institute of Scientific and Technical Information of China (English)

    杨兴华; 杨喜军; 张哲民; 姜建国

    2012-01-01

    One-cycle control (OCC) is a kind of nonlinear control technique which integrates modulation algorithm and control strategy. Power converters using OCC have many advantages, such as simply control circuit, fast dynamic response and good immunity on input disturbance. Based on the analysis of operation principle of OCC and matrix rectifier, one kind of three-phase input current OCC strategy is proposed, which makes the three-phase input current to achieve balance in a switching cycle, and to realize unity input power factor. In order to make up the insufficiency of OCC on load disturbance suppression, a PID controller is added on output voltage control to improve load regulation. After completing the system simulation of OCC on matrix rectifier in Matlab/Simulink, one physical matrix rectifier system is realized using the digital integral technology and a new bootstrap power supply. The simulation analysis results and the experimental results prove theoretical analysis on the OCC model of matrix rectifier, and the control effects are satisfactory.%单周期控制(OCC)是一种同时综合调制算法与控制策略的非线性控制技术,采用该控制技术的电力电子变换器具有控制电路简单、动态响应速度快、抗输入干扰性能好等优点。在分析单周期控制原理与矩阵整流器工作原理的基础上,提出了一种三相输入电流的单周期控制策略,使三相输入电流在每个开关周期内达到平衡,实现矩阵整流器单位输入功率因数的控制效果,同时为了弥补单周期控制对负载扰动抑制能力的不足,增加输出电压PID控制环节,改善负载调整率。在利用Matlab/Simulink完成单周期控制的矩阵整流器系统仿真后,采用数字积分技术和新型自举电源驱动技术实现了单周期控制的矩阵整流器系统。仿真分析结果与实验结果验证了矩阵整流器单周期控制模型的理论分析是正确的,控制效果是良好的。

  12. In vitro starch digestibility and expected glycemic index of pound cakes baked in two-cycle microwave-toaster and conventional oven.

    Science.gov (United States)

    García-zaragoza, Francisco J; Sánchez-Pardo, María E; Ortiz-Moreno, Alicia; Bello-Pérez, Luis A

    2010-11-01

    Bread baking technology has an important effect on starch digestibility measured as its predicted glycemic index tested in vitro. The aim of this work was to evaluate the changes in predicted glycemic index of pound cake baked in a two-cycle microwave toaster and a conventional oven. The glycemic index was calculated from hydrolysis index values by the Granfeldt method. Non-significant differences (P > 0.05) were found in hydrolysis index (60.67 ± 3.96 for the product baked in microwave oven and 65.94 ± 4.09 for the product baked in conventional oven) and predicted glycemic index content (60.5 for product baked in microwave oven and 65 for the product baked in conventional oven) in freshly-baked samples. Results clearly demonstrate that the baking pound cake conventional process could be replicated using a two-cycle multifunction microwave oven, reducing the traditional baking time. Further research is required in order to achieve pound cake crumb uniformity. PMID:20367217

  13. Fabrication of ultrahigh density metal-cell-metal crossbar memory devices with only two cycles of lithography and dry-etch procedures

    KAUST Repository

    Zong, Baoyu

    2013-05-20

    A novel approach to the fabrication of metal-cell-metal trilayer memory devices was demonstrated by using only two cycles of lithography and dry-etch procedures. The fabricated ultrahigh density crossbar devices can be scaled down to ≤70 nm in half-pitch without alignment issues. Depending on the different dry-etch mechanisms in transferring high and low density nanopatterns, suitable dry-etch angles and methods are studied for the transfer of high density nanopatterns. Some novel process methods have also been developed to eliminate the sidewall and other conversion obstacles for obtaining high density of uniform metallic nanopatterns. With these methods, ultrahigh density trilayer crossbar devices (∼2 × 1010 bit cm-2-kilobit electronic memory), which are composed of built-in practical magnetoresistive nanocells, have been achieved. This scalable process that we have developed provides the relevant industries with a cheap means to commercially fabricate three-dimensional high density metal-cell-metal nanodevices. © 2013 IOP Publishing Ltd.

  14. Performance analyses of oxy-fuel power generation systems including CO2 capture: comparison of two cycles using different recirculation fluids

    International Nuclear Information System (INIS)

    With increasing concerns on global warming, reduction of CO2 emission has become a hot issue and studies of CO2 capture and storage (CCS) technology in power plant applications are in progress. Oxy-fuel combustion is one of the several available technologies that intend to capture CO2. Since the combustion gas consists mainly of CO2 and H2O in oxy-fuel combustion systems, it is easy to separate CO2 from the flue gas using a simple mechanical method instead of complex chemical processes. There have been suggested a couple of power cycles using different recirculation fluids for combustion dilution purpose. This study aimed to investigate the influence of CO2 capture on the performance of two promising oxy-fuel combustion power cycles adopting H2O and CO2 as the recirculation fluid. Optimal integration between the carbon capture process and the power cycle was examined and the influences of carbon capture on the entire system performance were compared for the two cycles

  15. Design and Implementation of the PWM Current Controller Based on One Cycle Control%基于单周期控制的PWM电流控制系统设计与实现

    Institute of Scientific and Technical Information of China (English)

    明鑫

    2016-01-01

    针对无刷直流电机(BLDC)驱动器的电流控制问题,提出了一种改进的基于单周控制的低成本转子位置估算方法。该估算方法以真实反电势过零点的检测为依据,这些真实反电势过零点可直接通过检测相端和直流环节中点之间的电压来提取,无需电机中性点电压。电流控制系统通过一种低成本的通用自动电压调整微控制器(Atmega8)来实现。MATLAB仿真和实验测试结果均显示相比传统的滞环控制器方法,改进后的PWM(脉冲宽度调制)无刷直流电机电流控制系统在稳态和瞬态两种情况下表现出更好的性能。%According to the current brushless DC motor drive control problem,a low cost improved method to esti⁃mate the rotor position based on one cycle control is presented. The estimation method is based on real back EMF zero crossing detection. The back EMF zero crossing detection can be extracted directly through the voltage between phase end and the DC link midpoint without the motor neutral point voltage. The current control system can be achieved by the general automatic voltage regulation of a kind of low cost microcontroller(Atmega8). MATLAB simu⁃lation and practical test results showed that compared it with the traditional Hysteresis controller method,the im⁃proved PWM(Pulse Width Modulation)brushless DC motor control system exhibited better performance in two cases of the steady state and the transient current.

  16. Treatment option for infertility following failed to two cycles intrauterine insemination.%2次宫腔内人工授精失败后助孕治疗方案的选择

    Institute of Scientific and Technical Information of China (English)

    张敏; 杜敏; 王箭; 罗群芳

    2011-01-01

    目的 探讨2次官腔内人工授精(IUI)失败后助孕治疗方案的选择合理化.方法 回顾性分析2001-2009年具有实施2个周期IUI失败病史病例211例,根据其后的助孕方式分为4组:药物保守治疗组、IUI组、IVF组、腹腔镜组.对比其不孕病因分布、年龄、临床妊娠率.结果 腹腔镜组通过手术发现输卵管盆腔因素及子宫内膜异位症因素比例合约36.01%,其他三组该两项不孕因素合计平均为12.14%,差异有统计学意义.IUI 3次周期以上的临床妊娠率仅为7.67%,较同期本中心IUI 2次周期以下的临床妊娠率明显降低;IVF组临床妊娠率为35.39%,较其他三组明显偏高,差异有统计学意义.结论 IUI治疗一般不超过2次,如不能妊娠,应对不孕因素再次进行分析评价,不要盲目重复进行IUI,使其错过更有效的、更及时的助孕方式.%ObjectiveTo explore rationalization of treatment option for infertility following failed to two cycles intrauterine insemination. Methods 211 patients following failed to two cycles intrauterine insemination from 2001 to 2009 were analyzedretrospectively. The patients were divided into 4 groups according treatment option for infertility: medicament group, IUI group, IVF group, laparoscope group. The pathogeny of infertility, age, the rate of clinical pregnancy were compared among the groups. Results The patients in laparoscope group were found fallopian tube disease and endometriosis (36.01%), the rate was 12.t4% in another three groups, there were statistical difference.The rate of clinical pregnancy following three cycles intrauterine insemination was 7.67%, it was lower than the cycles less two times intrauterine insemination. The rate of clinical pregnancy in IVF group was significantly higher than in other groups. Conclusion IUI were not suggested more than two cycles, if not succeeded, infertility factor should be analyzed, and the other method should be employed.

  17. Meta-Analysis Combines Affymetrix Microarray Results Across Laboratories

    OpenAIRE

    Doerge, R. W.; John R. Stevens

    2005-01-01

    With microarray technology becoming more prevalent in recent years, it is now common for several laboratories to employ the same microarray technology to identify differentially expressed genes that are related to the same phenomenon in the same species. Although experimental specifics may be similar, each laboratory will typically produce a slightly different list of statistically significant genes, which calls into question the validity of each gene list (i.e. which list is best). A statist...

  18. RELAÇÕES HÍDRICAS EM DOIS HÍBRIDOS DE MILHO SOB DOIS CICLOS DE DEFICIÊNCIA HÍDRICA WATER RELATIONS IN TWO HYBRIDS OF CORN UNDER TWO CYCLES OF WATER STRESS

    Directory of Open Access Journals (Sweden)

    CARLOS PIMENTEL

    1999-11-01

    Full Text Available Neste trabalho foram estudadas as relações hídricas de dois híbridos de milho (Zea mays L., em casa de vegetação: o IAC 8222 (híbrido com tolerância ambiental e o DINA 10 (híbrido comum; submetidos a um ou a dois ciclos de estresse, aos 30 e 46 DAP. O IAC 8222 manteve o potencial hídrico de folha (psihf superior ao do DINA no primeiro ciclo de estresse e no segundo ciclo, em plantas que sofreram os dois ciclos (com endurecimento, no sexto e último dia de deficiência hídrica, não havendo diferenças em relação ao conteúdo hídrico relativo (CHR entre os híbridos. Houve um aumento da concentração de açúcares solúveis e de aminoácidos com a deficiência hídrica, sem diferenças entre os híbridos no primeiro ciclo de déficit hídrico, e com aumento significativo somente na concentração de aminoácidos no DINA 10 submetido aos dois ciclos, no último dia do segundo ciclo. A concentração de K+ não variou nem com os ciclos nem entre híbridos. Portanto, só houve diferenças na acumulação de solutos osmóticos entre os híbridos, quanto ao teor de aminoácidos no DINA 10 submetido aos dois ciclos, no segundo ciclo. Contudo, o IAC 8222 manteve o seu psihf alto, podendo ter promovido um ajuste do coeficiente de extensibilidade de parede, que foi acentuado com o endurecimento.A study was conducted to evaluate the water relations of two corn (Zea mays L. hybrids in a greenhouse experiment: IAC 8222 (hybrid adapted to environmental stress and DINA 10 (common hybrid, under one or two cycles of water stress applied at 30 and 46 days after sowing. During the first water deficit cycle, and at the second cycle for plants submitted to both cycles, the leaf water potential (psihf of IAC 8222 was higher than the psihf of DINA 10, at the 6th and last day of water stress, with no difference for the relative water content (CHR between the hybrids. The soluble sugars and amino acids accumulated during the water stress, but no

  19. One-cycle Control Strategy of Three-phase PV Inverters Based on Negative Sequence Voltage Feedforward Compensation Under Unbalanced Input Voltage Conditions%负序电压前馈补偿的三相光伏逆变器不平衡单周控制策略

    Institute of Scientific and Technical Information of China (English)

    徐友; 郑建勇; 梅军; 姚磊

    2012-01-01

    Considering frequent occurrence of grid unsymmetrical faults, an unbalanced one cycle control strategy for three-phase grid-connected photovoltaic (PV) inverters based on negative sequence components of voltage feedforward compensation is developed, and the corresponding control system is designed. The novel control strategy compensates feedback grid currents by negative sequence components of grid voltages to regulate the instantaneous active power to a constant value without any ripple, and the harmonics can be eliminated. Therefore, the parameter tuning of proportional integral (PI) controllers is simplified and the extraction of positive and negative sequence components of line currents is not required. Experimental results indicates that the proposed inverter control system adopts only one conventional PI controller to eliminate the second harmonic waves of the DC voltage and distortion of line currents under unbalanced input grid voltage conditions. As well as the control system has achieved perfect static and dynamic characteristics.%鉴于电网不对称故障时有发生,提出一种基于负序电压前馈补偿的三相光伏并网逆变器不平衡单周控制策略,并设计了三相PWM逆变器不平衡单周控制系统.该控制策略对并网电流反馈量进行电网负序电压前馈补偿,可实现脉宽调制逆变器恒功率控制,大大简化了控制器的参数整定,且无需计算并网电流正、负序分量.实验结果表明,该控制策略仅使用一个传统PI控制器即可从根本上抑制电网电压不平衡时逆变器直流侧电压2次谐波和并网电流畸变,同时获得了较理想的静态特性和动态特性.

  20. Dopad strukturace studií dle Boloňského procesu na vzdělávání učitelů v České republice / Impact of the Bologna process two-cycle implementation on teacher education in the Czech Republic

    OpenAIRE

    Stanislav Bendl; Hana Voňková; Michal Zvírotský

    2013-01-01

    As a consequence of the Bologna process, five-year master’s teacher education programmes have been divided into three-year bachelor’s and two-year master’s studies in the Czech Republic. The aim of this paper is to describe the development of the two-cycle implementation in teacher education programmes in the Czech Republic and present survey results about the opinions of both the academic staff and students at the Faculty of Education of Charles University in Prague on the implementation. In...

  1. nuID: a universal naming scheme of oligonucleotides for Illumina, Affymetrix, and other microarrays

    Directory of Open Access Journals (Sweden)

    Kibbe Warren A

    2007-05-01

    Full Text Available Abstract Background Oligonucleotide probes that are sequence identical may have different identifiers between manufacturers and even between different versions of the same company's microarray; and sometimes the same identifier is reused and represents a completely different oligonucleotide, resulting in ambiguity and potentially mis-identification of the genes hybridizing to that probe. Results We have devised a unique, non-degenerate encoding scheme that can be used as a universal representation to identify an oligonucleotide across manufacturers. We have named the encoded representation 'nuID', for nucleotide universal identifier. Inspired by the fact that the raw sequence of the oligonucleotide is the true definition of identity for a probe, the encoding algorithm uniquely and non-degenerately transforms the sequence itself into a compact identifier (a lossless compression. In addition, we added a redundancy check (checksum to validate the integrity of the identifier. These two steps, encoding plus checksum, result in an nuID, which is a unique, non-degenerate, permanent, robust and efficient representation of the probe sequence. For commercial applications that require the sequence identity to be confidential, we have an encryption schema for nuID. We demonstrate the utility of nuIDs for the annotation of Illumina microarrays, and we believe it has universal applicability as a source-independent naming convention for oligomers. Reviewers This article was reviewed by Itai Yanai, Rong Chen (nominated by Mark Gerstein, and Gregory Schuler (nominated by David Lipman.

  2. Evaluating the performance of Affymetrix SNP Array 6.0 platform with 400 Japanese individuals

    Directory of Open Access Journals (Sweden)

    Uehara Yasuka

    2008-09-01

    Full Text Available Abstract Background With improvements in genotyping technologies, genome-wide association studies with hundreds of thousands of SNPs allow the identification of candidate genetic loci for multifactorial diseases in different populations. However, genotyping errors caused by genotyping platforms or genotype calling algorithms may lead to inflation of false associations between markers and phenotypes. In addition, the number of SNPs available for genome-wide association studies in the Japanese population has been investigated using only 45 samples in the HapMap project, which could lead to an inaccurate estimation of the number of SNPs with low minor allele frequencies. We genotyped 400 Japanese samples in order to estimate the number of SNPs available for genome-wide association studies in the Japanese population and to examine the performance of the current SNP Array 6.0 platform and the genotype calling algorithm "Birdseed". Results About 20% of the 909,622 SNP markers on the array were revealed to be monomorphic in the Japanese population. Consequently, 661,599 SNPs were available for genome-wide association studies in the Japanese population, after excluding the poorly behaving SNPs. The Birdseed algorithm accurately determined the genotype calls of each sample with a high overall call rate of over 99.5% and a high concordance rate of over 99.8% using more than 48 samples after removing low-quality samples by adjusting QC criteria. Conclusion Our results confirmed that the SNP Array 6.0 platform reached the level reported by the manufacturer, and thus genome-wide association studies using the SNP Array 6.0 platform have considerable potential to identify candidate susceptibility or resistance genetic factors for multifactorial diseases in the Japanese population, as well as in other populations.

  3. Comparison of Gene Expression in Leymus Tiller and Rhizome Meristems Using Heterologous Affymetrix Wheat and Barley Gene Chips

    Science.gov (United States)

    Perennial Leymus wildrye tillers and rhizomes develop from similar underground axillary meristems, but display different response to gravity and perhaps other cues that govern branch angle and overall patterns of subterranean growth. Corresponding variation in growth habit is an important component...

  4. The D=11 Supermembrane wrapped on a two cycle and the $KKB$ Superparticle in D=9

    CERN Document Server

    Hatcher, N; Stephany, J

    2005-01-01

    We consider the action of the D=11 supermembrane wrapping a compactified sector of the target space in such a way that a non trivial central charge in the SUSY algebra is induced. We show that the dynamics of the center of mass corresponds to a superparticle in D=9 with additional fermionic terms associated to the central charges . We perform the covariant quantization of this system following a direct approach which introduces an equivalent action for the system which has only first class constraints allowing to obtain the space of physical states in a covariant way. The resulting multiplet contains $2^8$ states corresponding to to a $KKB$ ultrashort multiplet.

  5. Example of a quadratic system with two cycles appearing in a homoclinic loop bifurcation

    Science.gov (United States)

    Rousseau, Christiane

    We give here a planar quadratic differential system depending on two parameters, λ, δ. There is a curve in the λ-δ space corresponding to a homoclinic loop bifurcation (HLB). The bifurcation is degenerate at one point of the curve and we get a narrow tongue in which we have two limit cycles. This is the first example of such a bifurcation in planar quadratic differential systems. We propose also a model for the bifurcation diagram of a system with two limit cycles appearing at a singular point from a degenerate Hopf bifurcation, and dying in a degenerate HLB. This model shows a deep duality between degenerate Hopf bifurcations and degenerate HLBs. We give a bound for the maximal number of cycles that can appear in certain simultaneous Hopf and homoclinic loop bifurcations. We also give an example of quadratic system depending on three parameters which has at one place a degenerate Hopf bifurcation of order 3, and at another place a Hopf bifurcation of order 2 together with a HLB. We characterize the planar quadratic systems which are integrable in the neighbourhood of a homoclinic loop.

  6. Mid-infrared strong-field ionization of clusters using two-cycle pulses

    CERN Document Server

    Schütte, Bernd; Austin, Dane R; Brahms, Christian; Strüber, Christian; Witting, Tobias; Tisch, John W G; Marangos, Jonathan P

    2016-01-01

    We study mid-infrared strong-field ionization of rare-gas clusters ($10^3$ to $10^5$ atoms) in the impulsive limit using 12 fs laser pulses. The emission of fast electrons with kinetic energies exceeding 3 keV is observed at 1.8 $\\mu$m and an intensity of $1\\times 10^{15}$ W/cm$^2$, whereas only electrons below 500 eV are observed at 800 nm using a similar intensity and pulse duration. Fast electrons are preferentially emitted along the laser polarization direction, indicating that they are driven out from the cluster by the laser field via direct and rescattering processes within a few femtoseconds. In contrast to previous near-infrared strong-field ionization experiments in clusters using 200-1000 fs laser pulses, the yield of fast electrons decreases with increasing pulse duration. Scaling to longer wavelengths is expected to result in a highly directional current of hot electrons on a few-femtosecond timescale.

  7. Role of electron quantum paths in high-harmonics by two-cycle pulses

    International Nuclear Information System (INIS)

    Full text: The generation of high order harmonics can be considered as a tool to understand and exploit the single electron dynamics within the optical cycle. The selection of a suitable trajectory and its sensitivity to the carrier envelope phase of the laser pulse is here investigated experimentally and theoretically. Refs. 4 (author)

  8. Local Stability of Period Two Cycles of Second Order Rational Difference Equation

    Directory of Open Access Journals (Sweden)

    S. Atawna

    2012-01-01

    Full Text Available We consider the second order rational difference equation   n = 0,1,2,…, where the parameters are positive real numbers, and the initial conditions are nonnegative real numbers. We give a necessary and sufficient condition for the equation to have a prime period-two solution. We show that the period-two solution of the equation is locally asymptotically stable. In particular, we solve Conjecture 5.201.2 proposed by Camouzis and Ladas in their book (2008 which appeared previously in Conjecture 11.4.3 in Kulenović and Ladas monograph (2002.

  9. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen Juul; Kostakoglu, Lale; Hutchings, Martin;

    2015-01-01

    We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) s...

  10. Fabrication and testing of a ceramic two-cycle diesel engine. Final report, 29 November 1983-31 January 1986

    Energy Technology Data Exchange (ETDEWEB)

    MacBeth, J.W.

    1986-03-31

    The project effort was focused around evaluating the friction horsepower performance of a single-cylinder two-stroke opposed-piston diesel engine, fabricated from conventional metal components and then with the substitution of ceramic components for the cylinder liner and pistons. The ceramic configurations were run ringless and without cylinder lubrication. Frictional torque measurements were 50% lower than in the standard baseline case.

  11. AdS solutions in gauge supergravities and the global anomaly for the product of complex two-cycles

    International Nuclear Information System (INIS)

    Cohomological methods are applied for the special set of solutions corresponding to rotating branes in arbitrary dimensions, AdS black holes (which can be embedded in ten or eleven dimensions), and gauge supergravities. A new class of solutions is proposed, the Hilbert modular varieties, which consist of the 2n-fold product of the two-spaces Hn /Γ (where Hn denotes the product of n upper half-planes, H 2, equipped with the co-compact action of Γ is contained in SL(2, R)n) and (H n)*/Γ (where (H 2)*=H 2Γ and Γ is a congruence subgroup of SL(2, R) n). The cohomology groups of the Hilbert variety, which inherit a Hodge structure (in the sense of Deligne), are analyzed, as well as bifiltered sequences, weight and Hodge filtrations, and it is argued that the torsion part of the cuspidal cohomology is involved in the global anomaly condition. Indeed, in the presence of the cuspidal part, all cohomology classes can be mapped to the boundary of the space and the cuspidal contribution can be involved in the global anomaly condition. (orig.)

  12. Towards the Two-Cycle Degree Structure: Bologna, Reform and Path Dependency in German and Norwegian Universities

    Science.gov (United States)

    Kehm, Barbara M.; Michelsen, Svein; Vabo, Agnete

    2010-01-01

    This article describes and analyses changes made in the organisation of higher education studies in Germany and Norway, following the recommendations of the Bologna Declaration. In both countries, the characteristic modes of university study have been circumscribed by the tradition of Humboldtian values and ideals, albeit to a different extent. On…

  13. On the Period-Two Cycles of xn+1=(α+βxn+γxn-k/(A+Bxn+Cxn-k

    Directory of Open Access Journals (Sweden)

    S. Atawna

    2013-01-01

    Full Text Available We consider the higher order nonlinear rational difference equation xn+1=(α+βxn+γxn-k/(A+Bxn+Cxn-k,n=0,1,2,…, where the parameters α,β,γ,A,B,C are positive real numbers and the initial conditions x-k,…,x-1,x0 are nonnegative real numbers, k∈{1,2,…}. We give a necessary and sufficient condition for the equation to have a prime period-two solution. We show that the period-two solution of the equation is locally asymptotically stable.

  14. High quality sub-two cycle pulses from compression of supercontinuum generated in all-normal dispersion photonic crystal fiber.

    Science.gov (United States)

    Heidt, Alexander M; Rothhardt, Jan; Hartung, Alexander; Bartelt, Hartmut; Rohwer, Erich G; Limpert, Jens; Tünnermann, Andreas

    2011-07-18

    We demonstrate nonlinear pulse compression based on recently introduced highly coherent broadband supercontinuum (SC) generation in all-normal dispersion photonic crystal fiber (ANDi PCF). The special temporal properties of the octave-spanning SC spectra generated with 15 fs, 1.7 nJ pulses from a Ti:Sapphire oscillator in a 1.7 mm fiber piece allow the compression to 5.0 fs high quality pulses by linear chirp compensation with a compact chirped mirror compressor. This is the shortest pulse duration achieved to date from the external recompression of SC pulses generated in PCF. Numerical simulations in excellent agreement with the experimental results are used to discuss the scalability of the concept to the single-cycle regime employing active phase shaping. We show that previously reported limits to few-cycle pulse generation from compression of SC spectra generated in conventional PCF possessing one or more zero dispersion wavelengths do not apply for ANDi PCF. PMID:21934748

  15. Comparison of Nanostring nCounter® Data on FFPE Colon Cancer Samples and Affymetrix Microarray Data on Matched Frozen Tissues.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available The prognosis of colorectal cancer (CRC stage II and III patients remains a challenge due to the difficulties of finding robust biomarkers suitable for testing clinical samples. The majority of published gene signatures of CRC have been generated on fresh frozen colorectal tissues. Because collection of frozen tissue is not practical for routine surgical pathology practice, a clinical test that improves prognostic capabilities beyond standard pathological staging of colon cancer will need to be designed for formalin-fixed paraffin-embedded (FFPE tissues. The NanoString nCounter® platform is a gene expression analysis tool developed for use with FFPE-derived samples. We designed a custom nCounter® codeset based on elements from multiple published fresh frozen tissue microarray-based prognostic gene signatures for colon cancer, and we used this platform to systematically compare gene expression data from FFPE with matched microarray array data from frozen tissues. Our results show moderate correlation of gene expression between two platforms and discovery of a small subset of genes as candidate biomarkers for colon cancer prognosis that are detectable and quantifiable in FFPE tissue sections.

  16. In-core power sharing and fuel requirement study for a decommissioning Boiling Water Reactor using the linear reactivity model

    International Nuclear Information System (INIS)

    Highlights: • Linear reactivity model (LRM) was modified and applied to Boiling Water Reactor. • The power sharing and fuel requirement study of the last cycle and two cycles before decommissioning was implemented. • The loading pattern design concept for the cycles before decommissioning is carried out. - Abstract: A study of in-core power sharing and fuel requirement for a decommissioning BWR (Boiling Water Reactor) was carried out using the linear reactivity model (LRM). The power sharing of each fuel batch was taken as an independent variable, and the related parameters were set and modified to simulate actual cases. Optimizations of the last cycle and two cycles before decommissioning were both implemented; in the last-one-cycle optimization, a single cycle optimization was carried out with different upper limits of fuel batch power, whereas, in the two-cycle optimization, two cycles were optimized with different cycle lengths, along with two different optimization approaches which are the simultaneous optimization of two cycles (MO) and two successive single-cycle optimizations (SO). The results of the last-one-cycle optimization show that it is better to increase the fresh fuel power and decrease the thrice-burnt fuel power as much as possible. It also shows that relaxing the power limit is good to the fresh fuel requirement which will be reduced under lower power limit. On the other hand, the results of the last-two-cycle (cycle N-1 and N) optimization show that the MO is better than SO, and the power of fresh fuel batch should be decreased in cycle N-1 to save its energy for the next cycle. The results of the single-cycle optimization are found to be the same as that in cycle N of the multi-cycle optimization. Besides that, under the same total energy requirement of two cycles, a long-short distribution of cycle length design can save more fresh fuel

  17. Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential {sup 18}F-FDG PET/CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Ilhan; Kim, Byung Il; Choi, Chang Woon [Korea Institute of Radiological and Medical Sciences (KIRAMS), Departments of Nuclear Medicine, Seoul (Korea, Republic of); Kong, Chang-Bae [Korea Institute of Radiological and Medical Sciences (KIRAMS), Orthopedic Surgery, Seoul (Korea, Republic of); Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Orthopedic Surgery, Seoul (Korea, Republic of); Song, Won Seok; Cho, Wan Hyeong; Jeon, Dae-Geun; Lee, Soo-Yong [Korea Institute of Radiological and Medical Sciences (KIRAMS), Orthopedic Surgery, Seoul (Korea, Republic of); Koh, Jae-Soo [Korea Institute of Radiological and Medical Sciences (KIRAMS), Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences (KIRAMS), Departments of Nuclear Medicine, Seoul (Korea, Republic of); Korea Institute of Radiological and Medical Sciences (KIRAMS), Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2014-08-15

    We evaluated the potential of sequential fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after one cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma. A prospective study was conducted on 30 patients with osteosarcoma treated with two cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after one cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUV{sub max}), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen. A total of 17 patients (57 %) exhibited a poor histologic response after two cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and two cycles of chemotherapy, respectively. After one cycle of chemotherapy, SUV{sub max}, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47 mL or TLG ≥ 190 g after one cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98,p = 0.039). The sensitivity, specificity, and accuracy of these parameters were 71 %, 85 % and 77 %; and 71 %, 85 % and 77 %, respectively. The histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response. (orig.)

  18. Phase I/II study of preoperative chemo-radiotherapy (CT-RT) using twice daily radiation as concomitant boost during two cycles of taxol (T), cisplatin (C), 5-FU (F) in esophageal cancer: normal tissue tolerance and early results

    International Nuclear Information System (INIS)

    Purpose/Objective: Even though preoperative CT has failed to show survival benefit over surgery alone, preoperative CT-RT may provide such survival advantage. The goal of this study was to evaluate an intensified radiotherapy (RT) schedule in preoperative concurrent CT-RT for toxicities, resection rate, tumor downstaging, pathologic complete remission (CR) and treatment outcome. Materials and Methods: Eligibility included biopsy proven squamous or adenocarcinoma, T2-4N0-1M0 lesions, performance status ≤ 2 of ECOG scale, creatinine ≤ 2.0 mg/dl, WBC ≥ 2,500/μl, and platelets ≥ 75,000//μl. CT consisted of cisplatin (P) 20 mg/m2/day (d) x 5 d, 5-FU (F) 800 mg/m2/d continuous infusion x 5 d and Taxol (T) 75-125 mg/m2 (3 hour infusion) on d1 of each cycle. RT delivered 58.5 Gy/34 fractions (F) /5 weeks (wks) to the gross tumor volume by a combination of 45 Gy/25 F/5 wks to a large target volume (6 cm proximal and distal, and 3 cm radial margins beyond the gross tumor) and a boost dose of 13.5 Gy/9 F (1.5 Gy/F x 5 d with the first cycle [wk 1] and 1.5 Gy/F x 4 d with the second cycle [wk 5] of CT) with an interval of ≥ 5 hours between RT to the gross tumor (am) and large target volume (pm) as a means of concomitant boost. Staging work up included barium swallow, chest and head computed tomography, bone scan, esophagoscopy, and endoscopic ultrasound study (EUS). Results: Between April 1995 and February 1997, 38 patients (pts) with locoregional esophageal cancer have been entered into this study. Patient characteristics were as follows: Age 33-84 (median 63), male: female 30 : 8, adenocarcinoma: squamous cell carcinoma 31 : 7. Tumor stages by EUS included T2N0 11 (29%), T2N1 3 (8%), T3N0 14 (37%), T3N1 8 (21%) and T4N0 2 (5%). Taxol dose was escalated from 75 mg/m2 (7 pts) to 125 mg/m2 (5 pts) at which dose limiting toxicities were observed in (3(5)) pts (myocardial infarction, pneumonia, grade 4 neutropenia). The remaining 26 pts have been treated with T 100 mg/m2. Absolute neutrophile and platelet counts at nadir were 1,369/μl and 115,000/μl, and 1,035/μl and 81,000/μl for the first and second cycles of CT respectively. Grade (3(4)) esophagitis which was observed in 60% of pts was managed effectively with nutritional support. Thirty two of 38 pts (excluding 4 pts with new metastatic disease, 1 septic death, 1 death from hemorrhage in brain) were subjected to surgery and able to undergo complete resection (84%). Operative mortality was 6% ((2(32))) and overall treatment related mortality was 11% ((4(38))). Tumor downstaging and pathologic complete remission were obtained in 66% ((21(32))) and 38% ((12(32))) of pts respectively. Thirty of 38 pts (79%) remain free of relapse and median survival time has not reached. Conclusion: The concurrent CT (PFT regimen)-RT with the intensified RT dose schedule by concomitant boost seems an effective treatment with acceptable toxicity at the level of Taxol dose 100 mg/m2. Potential impact on survival of 66% rate of tumor downstaging and 38% rate of pathologic CR remains to be evaluated. Concomitant boost RT as a means of intensifying RT and exploiting chemo-radiation interaction in CT-RT deserves further study

  19. RELAÇÕES HÍDRICAS EM DOIS HÍBRIDOS DE MILHO SOB DOIS CICLOS DE DEFICIÊNCIA HÍDRICA WATER RELATIONS IN TWO HYBRIDS OF CORN UNDER TWO CYCLES OF WATER STRESS

    OpenAIRE

    CARLOS PIMENTEL

    1999-01-01

    Neste trabalho foram estudadas as relações hídricas de dois híbridos de milho (Zea mays L.), em casa de vegetação: o IAC 8222 (híbrido com tolerância ambiental) e o DINA 10 (híbrido comum); submetidos a um ou a dois ciclos de estresse, aos 30 e 46 DAP. O IAC 8222 manteve o potencial hídrico de folha (psihf) superior ao do DINA no primeiro ciclo de estresse e no segundo ciclo, em plantas que sofreram os dois ciclos (com endurecimento), no sexto e último dia de deficiência hídrica, não havendo ...

  20. Some aspects of simultaneously flying Topex Follow-On in a Topex orbit with Geosat Follow-On in a Geosat orbit

    Science.gov (United States)

    Parke, Michael E.; Born, George; Mclaughlin, Craig

    1994-01-01

    The advantages of having Geosat Follow-On in a Geosat orbit flying simultaneously with Topex Follow-On in a Topex/Poseidon orbit are examined. The orbits are evaluated using two criteria. The first is the acute crossover angle. This angle should be at least 40 degrees in order to accurately resolve the slope of sea level at crossover locations. The second is tidal aliasing. In order to solve for tides, the largest constituents should not be aliased to a frequency lower than two cycles/year and should be at least one cycle discrete from one another and from exactly two cycles/year over the mission life. The results show that TFO and GFO in these orbits complement each other. Both satellites have large crossover angles over a wide latitude range. In addition, the Topex orbit has good aliasing characteristics for the M2 and P1 tides for which the Geosat orbit has difficulty.

  1. Polarization gating of high harmonic generation in the water window

    Science.gov (United States)

    Li, Jie; Ren, Xiaoming; Yin, Yanchun; Cheng, Yan; Cunningham, Eric; Wu, Yi; Chang, Zenghu

    2016-06-01

    We implement the polarization gating (PG) technique with a two-cycle, 1.7 μm driving field to generate an attosecond supercontinuum extending to the water window spectral region. The ellipticity dependence of the high harmonic yield over a photon energy range much broader than previous work is measured and compared with a semi-classical model. When PG is applied, the carrier-envelope phase (CEP) is swept to study its influence on the continuum generation. PG with one-cycle (5.7 fs) and two-cycle (11.3 fs) delay are tested, and both give continuous spectra spanning from 50 to 450 eV under certain CEP values, strongly indicating the generation of isolated attosecond pulses in the water window region.

  2. Evolution of geomagnetic aa index near sunspot minimum

    OpenAIRE

    Kane, R. P.

    2002-01-01

    The smoothed values of the minima of sunspot number Rz and the geomagnetic index aa were compared for sunspot cycles 12–23. In one cycle, aa(min) occurred earlier than Rz(min), but remained at that low from a few months before Rz(min) to a few months after Rz(min). In two cycles, Rz(min) and aa(min) coincided within a month or two. In nine cycles, aa(min) occurred more than three months later than Rz(min). The aa(min) coincided with the minima of some solar radio e...

  3. A q-deformed logistic map and its implications

    International Nuclear Information System (INIS)

    A new q-deformed logistic map is proposed and it is found to have concavity in parts of the x-space. Its one-cycle and two-cycle non-trivial fixed points are obtained which are found to be qualitatively and quantitatively different from those of the usual logistic map. The stability of the proposed q-logistic map is studied using the Lyapunov exponent, and with a change in the value of the deformation parameter q, one is able to go from the chaotic to regular dynamical regime. The implications of this q-logistic map on Parrondo's paradox are examined.

  4. Uranium recovery from phosphates in Romania

    International Nuclear Information System (INIS)

    The history of laboratory and pilot-scale research work carried out in Romania is reviewed. Based on this work, three industrial-scale uranium recovery units have been built adjacent to the existing plants that produce phosphoric acid for fertilizer production. The process described uses solvent extraction for recovering uranium from phosphoric acid (sulfuric acid attack) and from phosphonitric acid (nitric acid attack). The extractant used is either a DEPA-TOPO mixture or a mixture of DEPA-TBP. The method selected for the industrial-scale units is a ''one-cycle, extraction-stripping process'' that differs from the ''two-cycle, extraction stripping process'' developed by the Oak Ridge National Laboratory (ORNL). In the ''one-cycle method'' both uranium and the rare earths are co-extracted and then selectively stripped by techniques that simultaneously produce precipitates. The first stripping operation selectively recovers a rare earth precipitate. Uranium is obtained from the second-stage stripping operation as ''green cake'' (a fluoride of U4+), which can be readily transformed to high purity UFO6. The treated phosphoric acid produces a triple superphosphate (TSP) of low radioactivity and diammonium phosphate (DAP) of no radioactivity. Three uranium recovery plants have been built adjacent to the existing phosphoric acid plants and are to be put into operation soon. Each plant can produce approximately 30 tonnes per year of uranium. The technology for conversion of the ''green cake'' to nuclear grade diuranate has also been finalized. Estimates indicate tha the ''one-cycle extraction-stripping process'' has a lower capital investment cost than the ''two-cycle extraction-stripping process'', and the projected operating costs are 25-30 US$/kg of U. (author). 8 refs, 2 figs

  5. Uranium recovery from phosphonitric solution

    International Nuclear Information System (INIS)

    Uranium recovery based on ORNL two-cycle extraction stripping process is carried out in USA, Belgium and Taiwan. In Romania an one-cycle extraction stripping process was developed both for phosphoric and phosphonitric acid. In the latter case a technology for obtaining two products, an uranium concentrate (green cake) and a rare earth concentrate, was established. The phosphonitric acid resulting from the process of nitric acid attack of phosphate rock is clarified and the extraction of uranium and rare earth are carried out in a mixture of di-(2-ethylhexyl) phosphate and tri-n-butylphosphate (or tri-n-octylphosphide oxide) in kerosene. Rare earths and uranium are stripped and simultaneously precipitated as fluorides in two stages. An intermediate scrubbing stage is required in order to eliminate the partially extracted nitric acid. (authors)

  6. Microstructure evolution and deformation mechanisms of the electroslag refined-continuous directionally solidified (ESR-CDS{sup ®}) superalloy Rene88DT during isothermal compression

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Rui [Superalloys Department, Central Iron & Steel Research Institute, Beijing 100081 (China); Li, Fulin, E-mail: lifulin1016@sina.com [Superalloys Department, Central Iron & Steel Research Institute, Beijing 100081 (China); Yin, Fajie; Feng, Di; Tian, Zhiling [Superalloys Department, Central Iron & Steel Research Institute, Beijing 100081 (China); Chang, Litao [School of Materials Science and Engineering, Xi' an University of Technology, Xi' an 710048 (China)

    2015-06-25

    The microstructure evolution and deformation mechanisms of alloy Rene88DT prepared by ESR-CDS{sup ®} during isothermal compression have been investigated by optical microscopy (OM), electron back scattered diffraction (EBSD) and transmission electron microscopy (TEM). The results showed that two cycles of dynamic recrystallization (DRX) occurred during the compressive deformation of the sample at super-solvus temperature with total true strain of 1.2, and this led to a near completely recrystallized fine-grained microstructure. For samples deformed at sub-solvus temperature, only one cycle of DRX occurred during compression with total true strain of 1.2, resulting in a partial recrystallized microstructure, and large misorientation formed in the un-recrystallized coarse grains. DRX is mainly initiated at the columnar grain boundaries or stimulated by the carbide particles within the grains. The main DRX mechanisms are grain boundary bulging and migration, second phase particles stimulation, sub-grain coarsening and migration.

  7. Microstructure evolution and deformation mechanisms of the electroslag refined-continuous directionally solidified (ESR-CDS®) superalloy Rene88DT during isothermal compression

    International Nuclear Information System (INIS)

    The microstructure evolution and deformation mechanisms of alloy Rene88DT prepared by ESR-CDS® during isothermal compression have been investigated by optical microscopy (OM), electron back scattered diffraction (EBSD) and transmission electron microscopy (TEM). The results showed that two cycles of dynamic recrystallization (DRX) occurred during the compressive deformation of the sample at super-solvus temperature with total true strain of 1.2, and this led to a near completely recrystallized fine-grained microstructure. For samples deformed at sub-solvus temperature, only one cycle of DRX occurred during compression with total true strain of 1.2, resulting in a partial recrystallized microstructure, and large misorientation formed in the un-recrystallized coarse grains. DRX is mainly initiated at the columnar grain boundaries or stimulated by the carbide particles within the grains. The main DRX mechanisms are grain boundary bulging and migration, second phase particles stimulation, sub-grain coarsening and migration

  8. Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Qianping Li; Jianjun Wang; Jun Zhang; Chengyi Lin

    2012-01-01

    Objective: The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer (NSCLC). Methods: This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010. The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation, radical surgery had been performed about three weeks after completion of chemotherapy, followed by received two cycles of chemotherapy. And the control group (52 cases) was treated at first with radical surgery, then treated with four cycles of chemotherapy. Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy. One cycle of gemcitabine combined with cisplatin regimen in-cluded gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1, day 2 and day 3 by intravenous infusion, with 21 days as one cycle. The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound. Efficacy and toxicity results were compared by two groups. Results: All patients were followed up for three months to two years. The surgical stage of the experimental group reduced, two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group, the difference was statistical significant. Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions, other complications included thrombocytopenia, leuko-penia, anemia, liver and kidney dysfunction were no significant difference in two groups. Conclusion: Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

  9. Sequential measurements of serum matrix metalloproteinase 9 to monitor chemotherapy responses in patients with advanced non-small-cell lung cancer

    Science.gov (United States)

    Qiao, Xiaojuan; Zhai, Xiaoran; Wang, Jinghui; Zhao, Xiaoting; Yang, Xinjie; Lv, Jialin; Ma, Li; Zhang, Lina; Wang, Yue; Zhang, Shucai; Yue, Wentao

    2016-01-01

    Background Matrix metalloproteinase 9 (MMP-9) plays an important role in tumor invasion and metastasis, including lung cancer. However, whether variations in serum MMP-9 levels can serve as a biomarker for monitoring chemotherapy curative effect remains unclear. This study was designed to investigate the association between variations in serum MMP-9 levels and chemotherapy curative effect in patients with lung cancer. Patients and methods A total of 82 patients with advanced lung cancer were included. All newly diagnosed patients were treated with platinum-based doublet chemotherapy. Serial measurements of serum MMP-9 levels were performed by enzyme-linked immunosorbent assay. In this manner, we chose four time points to examine the association, including before chemotherapy, and 3 weeks after the beginning of the first, second, and fourth cycles of chemotherapy. Results Compared with the serum level of MMP-9 before progressive disease, patients with progressive disease had elevated serum levels of MMP-9. Compared with the previous time point of collecting specimens, the serum levels of MMP-9 in the patients with a complete response/partial response/stable disease decreased or were maintained stable. The differences of variation in serum MMP-9 levels in patients with different chemotherapy curative effects were all statistically significant after one cycle, two cycles, and four cycles (after one cycle: P<0.001; after two cycles: P<0.001; after four cycles: P=0.01). However, patients with small-cell lung cancer did not exhibit similar test results. Conclusion The variation in serum MMP-9 levels in patients with non-small-cell lung cancer during chemotherapy was closely related to chemotherapy curative effect and could be useful to monitor chemotherapy curative effect for a small portion of patients. PMID:27330309

  10. Gene expression profiling of whole blood: Comparison of target preparation methods for accurate and reproducible microarray analysis

    Directory of Open Access Journals (Sweden)

    Choi Dongseok

    2009-01-01

    Full Text Available Abstract Background Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood, particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system. Results We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples. Conclusion RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can

  11. Radioembolisation with 90Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

    International Nuclear Information System (INIS)

    Radioembolisation with 90Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Twenty patients with metastatic lesions underwent radioembolisation. The 90Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β 2.5 Gy (NTL), 10 Gy (tumours); T1/2,eff = T1/2,phys = 64.2 h; T1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, ∝15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∝50 Gy (two cycles) and 65 Gy (three cycles). From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested. (orig.)

  12. Genome-Wide Association Analysis in Primary Sclerosing Cholangitis

    NARCIS (Netherlands)

    Karlsen, Tom H.; Franke, Andre; Melum, Espen; Kaser, Arthur; Hov, Johannes Roksund; Balschun, Tobias; Lie, Benedicte A.; Bergquist, Annika; Schramm, Christoph; Weismueller, Tobias J.; Gotthardt, Daniel; Rust, Christian; Philipp, Eva E. R.; Fritz, Teresa; Henckaerts, Liesbet; Weersma, Rinse K.; Stokkers, Pieter; Ponsioen, Cyriel Y.; Wijmenga, Cisca; Sterneck, Martina; Nothnagel, Michael; Hampe, Jochen; Teufel, Andreas; Runz, Heiko; Rosenstiel, Philip; Stiehl, Adolf; Vermeire, Severine; Beuers, Ulrich; Manns, Michael P.; Schrumpf, Erik; Boberg, Kirsten Muri; Schreiber, Stefan

    2010-01-01

    BACKGROUND & AIMS: We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide association analysis of single nucleotide polymorphism (SNP) markers. METHODS: A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA

  13. Sequential measurements of serum matrix metalloproteinase 9 to monitor chemotherapy responses in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Qiao XJ

    2016-06-01

    effects were all statistically significant after one cycle, two cycles, and four cycles (after one cycle: P<0.001; after two cycles: P<0.001; after four cycles: P=0.01. However, patients with small-cell lung cancer did not exhibit similar test results.Conclusion: The variation in serum MMP-9 levels in patients with non-small-cell lung cancer during chemotherapy was closely related to chemotherapy curative effect and could be useful to monitor chemotherapy curative effect for a small portion of patients.Keywords: prognosis, lung adenocarcinoma, lung squamous carcinoma, chemotherapy, treatment monitoring

  14. Radioembolisation with {sup 90}Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

    Energy Technology Data Exchange (ETDEWEB)

    Cremonesi, Marta; Ferrari, Mahila; Pedroli, Guido [European Institute of Oncology, Unit of Medical Physics, Milan (Italy); Bartolomei, Mirco; Arico, Demetrio; De Cicco, Concetta [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Orsi, Franco; Bonomo, Guido [European Institute of Oncology, Unit of Interventistic Radiology, Milan (Italy); Mallia, Andrew [Gamma Unit, Radiology Department, St. Luke' s Hospital (Malta); Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy)

    2008-11-15

    Radioembolisation with {sup 90}Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Twenty patients with metastatic lesions underwent radioembolisation. The {sup 90}Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting {alpha}/{beta} = 2.5 Gy (NTL), 10 Gy (tumours); T{sub 1/2,eff} = T{sub 1/2,phys} = 64.2 h; T{sub 1/2,rep} = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, {proportional_to}15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was {proportional_to}50 Gy (two cycles) and 65 Gy (three cycles). From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested. (orig.)

  15. e-Connections, vol. 1, no. 1; Spring 2006

    OpenAIRE

    2006-01-01

    VBI Hosts First Annual Research Symposium -- Core Laboratory Facility achieves National Custom Array Center status -- New Affymetrix scanner joins the team -- In the news -- Interview with Albert-László Barabási

  16. Genotype Data (Phase II) - D-HaploDB | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available re determined using Perlegen 281K arrays and Affymetrix 500K arrays Data analysis method The analyse...s by Perlegen 281K arrays are described in Kukita et al. (2005). The analyses by Affymetr

  17. Arabidopsis transcriptional responses differentiating closely related chemicals (herbicides) and cross-species extrapolation to Brassica

    Science.gov (United States)

    Using whole genome Affymetrix ATH1 GeneChips we characterized the transcriptional response of Arabidopsis thaliana Columbia 24 hours after treatment with five different herbicides. Four of them (chloransulam, imazapyr, primisulfuron, sulfometuron) inhibit acetolactate synthase (A...

  18. Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis.

    NARCIS (Netherlands)

    J.M. de Bont (Judith Maria); J.M. Kros (Johan); M.M. Passier (Monique); R.E. Reddingius (Roel); P.A.E. Sillevis Smitt (Peter); T.M. Luider (Theo); M.L. den Boer (Monique); R. Pieters (Rob)

    2008-01-01

    textabstractThe objective of this study was to identify differentially expressed and prognostically important genes in pediatric medulloblastoma and pediatric ependymoma by Affymetrix microarray analysis. Among the most discriminative genes, three members of the SOX transcription factor family were

  19. On designing heteroclinic networks from graphs

    Science.gov (United States)

    Ashwin, Peter; Postlethwaite, Claire

    2013-12-01

    Robust heteroclinic networks are invariant sets that can appear as attractors in symmetrically coupled or otherwise constrained dynamical systems. These networks may have a complicated structure determined to a large extent by the constraints and dimension of the system. As these networks are of great interest as dynamical models of biological and cognitive processes, it is useful to understand how particular directed graphs can be realised as attracting robust heteroclinic networks between states in phase space. This paper presents two methods of realising arbitrarily complex directed graphs as robust heteroclinic networks for flows generated by ODEs-we say the ODEs realise the graphs as heteroclinic networks between equilibria that represent the vertices. Suppose we have a directed graph on nv vertices with ne edges. The “simplex realisation” embeds the graph as an invariant set of a flow on an (nv-1)-simplex. This method realises the graph as long as it is one- and two-cycle free. The “cylinder realisation” embeds a graph as an invariant set of a flow on a (ne+1)-dimensional space. This method realises the graph as long as it is one-cycle free. In both cases we realise the graph as an invariant set within an attractor, and discuss some illustrative examples, including the influence of noise and parameters on the dynamics. In particular we show that the resulting heteroclinic network may or may not display “memory” of the vertices visited.

  20. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    International Nuclear Information System (INIS)

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m2 d1, 5FU 800 mg/m2 d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment

  1. Effects of MVP regimen on operation and cancer tisswes of Lung Cancer patients

    Directory of Open Access Journals (Sweden)

    Yunzhong ZHOU

    2008-02-01

    Full Text Available Background and objective Preoperative chemotherapy increases the difficulty and risk of patients爷operation. The aim of this study is to analyze the change of thoracic tissue, study the influence ofchemotherapy to operation, discuss the special aspects of surgical management and observe the pathological change of focus after chemotherapy. Methods 100 patients were chosen and randomly divided into two groups(operation first group, 50 cases; chemotherapy first group, 50 cases . Some patient爷s pathological sections were observed to investigate focus morphological influence of preoperative chemotherapy and the clinical response rate were compared with pathological response rate. Results It was showed that preoperative chemotherapy conduced different degree thoracic tissue fibrosis. Data statistics demonstrated that there were no significance difference of the operation time, blood loss during operation and drainage volume in first day after operation between two groups. The preoperativechemotherapy increased the difficulty of operation because of tissue fibrosis and scarification, but the risk could be avoided by skillful operation. In first operation group, there were various pathological changes in tumor tissue and the pathological response rate was not completely accordance with the clinical response rate. The focus pathological response rate of two cycles chemotherapy was more higher than that of one cycle chemotherapy. Conclusion Chemotherapy increases the risks of operation. Surgeons carefulness and better skills during operation are the key points to avoid the hazards of surgery. Two preoperative chemotherapy cycles are more suitable for the patients.

  2. Spring-fall asymmetry of substorm strength, geomagnetic activity and solar wind: Implications for semiannual variation and solar hemispheric asymmetry

    Science.gov (United States)

    Marsula, K.; Tanskanen, E.; Love, J.J.

    2011-01-01

    We study the seasonal variation of substorms, geomagnetic activity and their solar wind drivers in 1993–2008. The number of substorms and substorm mean duration depict an annual variation with maxima in Winter and Summer, respectively, reflecting the annual change of the local ionosphere. In contradiction, substorm mean amplitude, substorm total efficiency and global geomagnetic activity show a dominant annual variation, with equinoctial maxima alternating between Spring in solar cycle 22 and Fall in cycle 23. The largest annual variations were found in 1994 and 2003, in the declining phase of the two cycles when high-speed streams dominate the solar wind. A similar, large annual variation is found in the solar wind driver of substorms and geomagnetic activity, which implies that the annual variation of substorm strength, substorm efficiency and geomagnetic activity is not due to ionospheric conditions but to a hemispherically asymmetric distribution of solar wind which varies from one cycle to another. Our results imply that the overall semiannual variation in global geomagnetic activity has been seriously overestimated, and is largely an artifact of the dominant annual variation with maxima alternating between Spring and Fall. The results also suggest an intimate connection between the asymmetry of solar magnetic fields and some of the largest geomagnetic disturbances, offering interesting new pathways for forecasting disturbances with a longer lead time to the future.

  3. Evolution of geomagnetic aa index near sunspot minimum

    Directory of Open Access Journals (Sweden)

    R. P. Kane

    Full Text Available The smoothed values of the minima of sunspot number Rz and the geomagnetic index aa were compared for sunspot cycles 12–23. In one cycle, aa(min occurred earlier than Rz(min, but remained at that low from a few months before Rz(min to a few months after Rz(min. In two cycles, Rz(min and aa(min coincided within a month or two. In nine cycles, aa(min occurred more than three months later than Rz(min. The aa(min coincided with the minima of some solar radio emission indices originating in the solar corona. For sunspot cycles 21, 22, 23, the minimum of solar wind velocity V occurred 0–9 months later than the aa(min. The minimum of solar wind total magnetic field B occurred near Rz(min. The solar wind ion density N had maxima (instead of minima near Rz(min, and again near Rz(max, indicating a  ~5-year periodicity, instead of an 11-year periodicity. The maxima of aa, V and B occurred near Rz(max and/or later in the declining phase of Rz. The aa index was very well correlated with the functions BV and BV 2.Key words. Geomagnetism and paleomagnetism (time variations, diurnal to secular – time variations, secular and long term Interplanetary physics (interplanetary magnetic field

  4. Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission.

    Science.gov (United States)

    Basara, N; Schulze, A; Wedding, U; Mohren, M; Gerhardt, A; Junghanss, C; Peter, N; Dölken, G; Becker, C; Heyn, S; Kliem, C; Lange, T; Krahl, R; Pönisch, W; Fricke, H-J; Sayer, H G; Al-Ali, H; Kamprad, F; Niederwieser, D

    2009-04-01

    Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype. PMID:19151786

  5. Investigation of fatigue properties of granite asphalt mixtures containing hydrated lime

    Science.gov (United States)

    Wu, Shaopeng; Huang, Xu

    2010-03-01

    This paper presents the results of a laboratory study of evaluating the fatigue characteristics of granite asphalt mixtures (GAM) using different testing methods. In the study, the fatigue performances of GAM were evaluated with Superpave indirect tensile test (IDT) and four-point beam fatigue test. Specimens were conditioned by four different methods: (1) one cycle of freeze-thaw (F-T), (2) two cycles of F-T, (3) immersion in 60°C water bath for 30min (4) immersion in 60°C water bath for 48h, and contrastive analysis was made with unconditioned specimens. Investigation of moisture damage influence on the fatigue properties of GAM with and without Hydrated Lime (HL) was done. The results from this study indicated that both Superpave IDT and four-point beam fatigue test agreed with each other in ranking the fatigue property of GAM. Increasing F-T cycles or immersion time would decrease fatigue life in GAM, and the addition of HL was effective to prolong the fatigue life in GAM.

  6. Life cycle replacement by gene introduction under an allee effect in periodical cicadas.

    Directory of Open Access Journals (Sweden)

    Yukiko Nariai

    Full Text Available Periodical cicadas (Magicicada spp. in the USA are divided into three species groups (-decim, -cassini, -decula of similar but distinct morphology and behavior. Each group contains at least one species with a 17-year life cycle and one with a 13-year cycle; each species is most closely related to one with the other cycle. One explanation for the apparent polyphyly of 13- and 17-year life cycles is that populations switch between the two cycles. Using a numerical model, we test the general feasibility of life cycle switching by the introduction of alleles for one cycle into populations of the other cycle. Our results suggest that fitness reductions at low population densities of mating individuals (the Allee effect could play a role in life cycle switching. In our model, if the 13-year cycle is genetically dominant, a 17-year cycle population will switch to a 13-year cycle given the introduction of a few 13-year cycle alleles under a moderate Allee effect. We also show that under a weak Allee effect, different year-classes ("broods" with 17-year life cycles can be generated. Remarkably, the outcomes of our models depend only on the dominance relationships of the cycle alleles, irrespective of any fitness advantages.

  7. Facilitating functional annotation of chicken microarray data

    OpenAIRE

    Buza, Teresia J; Kumar, Ranjit; Gresham, Cathy R; Burgess, Shane C.; McCarthy, Fiona M

    2009-01-01

    Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO). However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually...

  8. Therapy of neuroendocrine carcinoma with Y-90 DOTA- preliminary results

    International Nuclear Information System (INIS)

    patient per one cycle, in the slow infusion in the physiological liquid (150 ml/15 min).Between the cycles, there was a time delay of 6-8 weeks. At 30 min before the therapy, patients began receiving the infusion of amino acids (arginine and lysine) which lasted 4h. Before that, all therapies with somatostatin analogues were withdrawn. One day after, 'bremsstrahlung' whole body imaging and particular planar images were performed with gamma camera (ECAM, Siemens). Results: All the patients had symptoms due to administration of amino acids (nausea) and one felt pain during the third and the fourth days after the therapy. Analysis of the 'bremsstrahlung' images showed uptake of the radiopharmaceutical in the liver, but most of the activity was observed in the regions of the 'hot spots' registered with previous 99mTc HYNIC TOC and 111In Octreoscan images. In two patients with pancreatic neuroendocrine carcinomas and liver metastases (one with peritoneal lymph metastases), after two cycles of the therapy, although clinical symptoms were improved, hormone production decreased as well as the tumor size, proliferation of the disease occurred. In the patient with resected bronchial carcinoid and liver metastases clinical symptoms were improved, hormones decreased, metastases were the same size in total, pointing out stable diseases, as well as in one patient with neuroendocrine carcinoma of unknown origin (liver and skeletal metastases) after two cycles of the therapy, and other three patients who received only one cycle of the therapy (two with carcinomas of unknown origin with liver metastases and one with gastrinoma). Up to now, there were no major clinical side effects regarding renal and hepatic function. Transient pancytopenia occurred in two patients. Conclusion: In spite of insufficient data, beneficial effects on clinical symptoms, hormone production and tumor proliferation were found, without major clinical side effects, except transient pancytopenia. Thus, according to

  9. Cognitive and Neurophysiological Effects of Non-invasive Brain Stimulation in Stroke Patients after Motor Rehabilitation.

    Science.gov (United States)

    D'Agata, Federico; Peila, Elena; Cicerale, Alessandro; Caglio, Marcella M; Caroppo, Paola; Vighetti, Sergio; Piedimonte, Alessandro; Minuto, Alice; Campagnoli, Marcello; Salatino, Adriana; Molo, Maria T; Mortara, Paolo; Pinessi, Lorenzo; Massazza, Giuseppe

    2016-01-01

    The primary aim of this study was to evaluate and compare the effectiveness of two specific Non-Invasive Brain Stimulation (NIBS) paradigms, the repetitive Transcranial Magnetic Stimulation (rTMS), and transcranial Direct Current Stimulation (tDCS), in the upper limb rehabilitation of patients with stroke. Short and long term outcomes (after 3 and 6 months, respectively) were evaluated. We measured, at multiple time points, the manual dexterity using a validated clinical scale (ARAT), electroencephalography auditory event related potentials, and neuropsychological performances in patients with chronic stroke of middle severity. Thirty four patients were enrolled and randomized. The intervention group was treated with a NIBS protocol longer than usual, applying a second cycle of stimulation, after a washout period, using different techniques in the two cycles (rTMS/tDCS). We compared the results with a control group treated with sham stimulation. We split the data analysis into three studies. In this first study we examined if a cumulative effect was clinically visible. In the second study we compared the effects of the two techniques. In the third study we explored if patients with minor cognitive impairment have most benefit from the treatment and if cognitive and motor outcomes were correlated. We found that the impairment in some cognitive domains cannot be considered an exclusion criterion for rehabilitation with NIBS. ERP improved, related to cognitive and attentional processes after stimulation on the motor cortex, but transitorily. This effect could be linked to the restoration of hemispheric balance or by the effects of distant connections. In our study the effects of the two NIBS were comparable, with some advantages using tDCS vs. rTMS in stroke rehabilitation. Finally we found that more than one cycle (2-4 weeks), spaced out by washout periods, should be used, only in responder patients, to obtain clinical relevant results. PMID:27445730

  10. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m2/d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC

  11. Peptide receptor radionuclide therapy of neuroendocrine tumors: Case series

    Directory of Open Access Journals (Sweden)

    Matović Milovan

    2012-01-01

    Full Text Available Background: Peptide Receptor Radionuclide Therapy (PRRT is novel and efficacious treatment of neuroendocrine tumors (NETs. Methods: Twenty-seven patients (14 females, 13 males, mean age 54.37±11.14 years; range 30-74 years with progressive, metastatic neuroendocrine tumors, were treated at least once during the period of 31 months (from July the 6th 2009 to February the 6th 2012 with PRRT in Nuclear Medicine Center, Clinical Center Kragujevac. There were carcinoids in 8 cases (6pts had intestinal and 2pts had lung carcinoid, medullary thyroid carcinoma in 5 cases, pancreatic carcinoma in 3 cases, paraganlioma in 2 cases, pheochromocytoma in 2 cases and in 7 cases primary tumors were not detected. We used 56 doses of different kinds of radiopharmaceuticals: 32 doses of 90Y-DOTATOC, 12 doses of 177Lu-DOTATATE, and 12 doses combining the 90Y-DODTATOC and 177Lu-DOTATATE. The PRRT was given in cycles: 12 pts received one cycle, 9 pts two cycles, 4 pts three cycles, 1 patient 4cycles and 2 pts five cycles of PRRT. The radioactivity was 3.2-7.40 GBq per cycle, and intervals between cycles ranged from 6 to 8 weeks. Results: The response to PRRT was assessed by morphological imaging (MSCT and MRI as well as by tumor marker follow up (CgA, 5-HIAA, catecholamines, CT and CEA. Seven pts (25.9% had partial response (PR, 17 pts (63.0% had stable disease (SD, and 3 pts (11.1% had progressive disease (PD. None of our patients had complete response (CR. All patients received PRRT under renal protection with amino acid infusions. In spite of this precaution, two patients with previously diagnosed diabetes mellitus suffered from serious deterioration of renal function after PRRT. Conclusion: The efficacy and safety of PRRT observed in our case series was in accordance with previously published data.

  12. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas

    Science.gov (United States)

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R.; Pitot, Henry C.; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles

    2015-01-01

    Summary 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m2 intravenously days 1–4 and 15–18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8–58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer. PMID:18278438

  13. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    International Nuclear Information System (INIS)

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age (±5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m2, and a continuous infusion of 5-fluorouracil, 1,000 mg/m2/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  14. Genetic Diversity of Maize Populations Developed by Two Kinds of Recurrent Selection Methods Investigated with SSR Markers

    Institute of Scientific and Technical Information of China (English)

    LI Lu-jiang; YANG Ke-cheng; PAN Guang-tang; RONG Ting-zhao

    2008-01-01

    Two cycles of biparental mass selection (MS) and one cycle of half-sib-S3 family combining selection (HS-S3) for yield were carried out in 2 synthetic maize populations P4C0 and P5C0 synchronously.The genetic diversity of 8 maize populations,including both the basic populations and their developed populations,were evaluated by 30 SSR primers.On the 30 SSR loci,a total of 184 alleles had been detected in these populations.At each locus,the number of alleles varied from 2 to 14,with an average of 6.13.The number and ratio of polymorphic loci in both the basic populations were higher than those of their developed populations,respectively.There was nearly no difference after MS but decreased after HS-S3 in both the basic populations in the mean gene heterozygosity.The mean genetic distance changed slightly after MS but decreased in a bigger degree after HS-S3 in both the basic populations.Analyses on the distribution of genetic distances showed that the ranges of the genetic distance were wider after MS and most of the genetic distances in populations developed by HS-S3 were smaller than those in both the basic populations.The number of genotypes increased after MS but decreased after HS-S3 in both the basic populations.The genetic diversity of intra-population was much more than genetic diversity of inter-population in both the basic populations.All these indexes demonstrated that the genetic diversity of populations after MS was similar to their basic populations,and the genetic diversity was maintained during MS,whereas the genetic diversity of populations decreased after HS-S3.This result indicated that heterogeneity between some of the individuals in the developed populations increased after MS,whereas the populations become more homozygotic after HS-S3.

  15. Large-scale in vitro expansion of human regulatory T cells with potent xenoantigen-specific suppression.

    Science.gov (United States)

    Jin, Xi; Lu, Yanrong; Zhao, Ye; Yi, Shounan

    2016-08-01

    Xenotransplantation is a potential solution to the organ donor shortage. Immunosuppression is required for successful application of xenotransplantation but may lead to infection and cancer. Thus, strategies for immune tolerance induction need to be developed. Polyclonal regulatory T cells (Treg) play a central role in the induction and maintenance of immune tolerance and have been shown to protect against islet xenograft rejection in vivo. However, global immune suppression may be mediated by polyclonal Treg immunotherapy and a simple method for in vitro expansion of xenoantigen-specific Treg for efficient Treg application becomes necessary. Human Treg isolated from peripheral blood mononuclear cells (PBMCs) were initially cultured with anti-CD3/CD28 beads, rapamycin and IL-2 for 7 days as polyclonal expansion. Expanded Treg were then cocultured with irradiated porcine PBMC as xenoantigen stimulation for three subsequent cycles with 7 days for each cycle in the presence of IL-2 and anti-CD3/CD28 beads. Treg phenotype and suppressive capacity were assessed after each cycle of xenoantigen stimulation. Treg expanded with one cycle of xenoantigen stimulation retained Treg suppressive phenotype but acquired no xenoantigen specificity along with poor expansion efficiency, whereas expansion with two-cycle xenoantigen stimulation resulted in not only more than 800-fold Treg expansion but highly suppressive xenoantigen-specific Treg with effector Treg phenotype. However further increase of stimulation cycles resulted in reduced Treg suppressive potency. This study provides a simple approach to obtain high numbers of xenoantigen-specific Treg for immune tolerance induction in xenotransplantation. PMID:25605448

  16. Lr34-mediated leaf rust resistance in wheat: transcript profiling reveals a high energetic demand supported by transient recruitment of multiple metabolic pathways

    Science.gov (United States)

    The wheat gene Lr34 confers partial resistance to all races of Puccinia triticina, the causal agent of wheat leaf rust. However, the biological basis for the exceptional durability of Lr34 is unclear. We used the Affymetrix GeneChip Wheat Genome Array to compare transcriptional changes of wheat in a...

  17. A trispecies Aspergillus microarray: Comparative transcriptomics of three Aspergillus species

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam; Vongsangnak, Wanwipa; Panagiotou, Gianni; Salazar, Margarita Pena; Lehmann, Linda Olkjær; Nielsen, Jens

    2008-01-01

    The full-genome sequencing of the filamentous fungi Aspergillus nidulans, Aspergillus niger, and Aspergillus oryzae has opened possibilities for studying the cellular physiology of these fungi on a systemic level. As a tool to explore this, we are making available an Affymetrix GeneChip developed...

  18. Evaluation of the performance of a p53 sequencing microarray chip using 140 previously sequenced bladder tumor samples

    DEFF Research Database (Denmark)

    Wikman, Friedrik; Lu, Ming-Lan; Andersen, Thomas Thykjær;

    2000-01-01

    available chip and describes a method to increase the specificity of the chip. Methods: DNA from 140 human bladder tumors was extracted and subjected to a multiplex-PCR before loading onto the p53 GeneChip from Affymetrix. The same samples were previously sequenced by manual dideoxy sequencing. In addition...

  19. An evaluation of the genetic-matched pair study design using genome-wide SNP data from the European population

    DEFF Research Database (Denmark)

    Lu, Timothy Tehua; Lao, Oscar; Nothnagel, Michael;

    2009-01-01

    Genetic matching potentially provides a means to alleviate the effects of incomplete Mendelian randomization in population-based gene-disease association studies. We therefore evaluated the genetic-matched pair study design on the basis of genome-wide SNP data (309,790 markers; Affymetrix Gene...

  20. Analysis of Large Genomic Data in Silico: The EPICNorfolk Study of Obesity

    DEFF Research Database (Denmark)

    Zhao, Jing Hua; Luan, Jian'an; Tan, Qihua;

    In human genetics, large-scale data are now available with advances in genotyping technologies and international collaborative projects. Our ongoing study of obesity involves Affymetrix 500k genechips on approximately 7000 individuals from the European Prospective Investigation of Cancer (EPIC...

  1. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC-INDUCED BLADDER CANCER

    Science.gov (United States)

    Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip® arrays ...

  2. Gene Expression Profiling and Functional Analysis of Spore Germination in Fusarium graminearum

    Science.gov (United States)

    A full genome study on conidia and ascospores has been carried out using F. graminearum Affymetrix GeneChips to compare gene expression during germination in complete medium at 0, 2, 8, 24 hours and after 10 days of drought stress. The total number of genes detected in at least one time point was si...

  3. Molecular Profiling of the Lateral Habenula in a Rat Model of Depression

    DEFF Research Database (Denmark)

    Christensen, Trine; Bouzinova, Elena; Wiborg, Ove

    2013-01-01

    Objective. This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level. Methods. Rat whole genome expression chips (Affymetrix) were used to detect gene expression regulations in the lateral...

  4. High-quality genotyping data from formalin-fixed, paraffin-embedded tissue on the drug metabolizing enzymes and transporters plus array

    NARCIS (Netherlands)

    Vos, H.I.; Straaten, T. van der; Coenen, M.J.H.; Flucke, U.E.; Loo, D.M.W.M. te; Guchelaar, H.J.

    2015-01-01

    The Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array covers 1936 markers in 231 genes involved in drug metabolism and transport. Blood- and saliva-derived DNA works well on the DMET array, but the utility of DNA from FFPE tissue has not been reported for this array. As the abi

  5. Characterizing the porcine transcriptional regulatory response to infection by Salmonella: identifying putative new NFkB direct targets through comparative bioinformatics.

    Science.gov (United States)

    We have collected data on host response to infection from RNA prepared from mesenteric lymph node of swine infected with either Salmonella enterica serovar Typhimurium (ST) or S. Choleraesuis (SC) using the porcine Affymetrix GeneChip. We identified 848 (ST) and 1,853 (SC) genes with statistical evi...

  6. Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling

    DEFF Research Database (Denmark)

    Bailey, Michael J; Coon, Steven L; Carter, John David;

    2009-01-01

    The pineal gland plays an essential role in vertebrate chronobiology by converting time into a hormonal signal, melatonin, which is always elevated at night. Here we have analyzed the rodent pineal transcriptome using Affymetrix GeneChip(R) technology to obtain a more complete description of pineal...

  7. Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Reppe, Sjur; Stilgren, Lis; Abrahamsen, Bo; Olstad, Ole K; Cero, Fadila; Brixen, Kim; Nissen-Meyer, Lise Sofie; Gautvik, Kaare M

    2007-01-01

    , kidney stones and metabolic bone disease. Our objective was to characterize changes in muscle and hematopoietic gene expression in patients with reversible mild PHPT after parathyroidectomy and possibly link molecular pathology to symptoms. Global mRNA profiling using Affymetrix gene chips was carried...

  8. A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and brassica napus

    Science.gov (United States)

    In this study, genome-wide expression profiling based on Affymetrix ATH1 arrays was used to identify discriminating responses of Arabidopsis thaliana to five herbicides, which contain active ingredients targeting two different branches of amino acid biosynthesis. One herbicide co...

  9. An orthologous transcriptional signature differentiates responses towards closely related chemicals in Arabidopsis thaliana and brassica napus

    Science.gov (United States)

    Herbicides are structurally diverse chemicals that inhibit plant-specific targets, however their off-target and potentially differentiating side-effects are less well defined. In this study, genome-wide expression profiling based on Affymetrix AtH1 arrays was used to identify dis...

  10. FULL-GENOME ANALYSIS OF ALTERNATIVE SPLICING IN MOUSE LIVER AFTER HEPATOTOXICANT EXPOSURE

    Science.gov (United States)

    Alternative splicing plays a role in determining gene function and protein diversity. We have employed whole genome exon profiling using Affymetrix Mouse Exon 1.0 ST arrays to understand the significance of alternative splicing on a genome-wide scale in response to multiple toxic...

  11. Frequent occurrence of uniparental disomy in colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, Claus Lindbjerg; Wiuf, Carsten; Kruhøffer, Mogens; Korsgaard, Marianne; Laurberg, Søren; Ørntoft, Torben Falck

    2007-01-01

      We used SNP arrays to identify and characterize genomic alterations associated with colorectal cancer (CRC). Laser microdissected cancer cells from 15 adenocarinomas were investigated by Affymetrix Mapping 10K SNP arrays. Analysis of the data extracted from the SNP arrays revealed multiple...

  12. 40 CFR 60.4345 - What are the requirements for the continuous emission monitoring system equipment, if I choose to...

    Science.gov (United States)

    2010-07-01

    ... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Stationary Combustion Turbines Monitoring... diluent monitor must complete a minimum of one cycle of operation (sampling, analyzing, and data...

  13. Methodological effects in kidney dosimetry in Lu177 radionuclide therapy

    International Nuclear Information System (INIS)

    Full text of publication follows. The aim of this study was to calculate the absorbed radiation dose in Lu177 DOTATATE treatments to the kidneys of patients with metastasized neuroendocrine tumours and compare the radiation doses obtained with small volume and kidney volumetric analysis. Methods: For 40 patients (23 males, 17 females) in 120 treatments absorbed doses to both kidneys were calculated. One patient had 5 cycles, 19 patients four cycles, 8 patients three cycles, 3 patients two cycles and 9 patients one cycle. Each patient received amino acid solution 30 minutes before and 8 hours after treatment to reduce the kidney dose. The injected activity was 7.4 GBq (88 treatments) or 3.7 GBq (32 treatments) and therapy cycles were repeated every eighth week. SPECT/CT studies were made 24 h, 48 h, 72 h (or 120 h) and 168 h after injection with Siemens Symbia T2. The window was set over the 208 keV photopeak. Attenuated and scatter corrected counts from kidney volumes were registered with volumetric analysis both from right and left kidney and also with small volume (4 cm3) technique. Dosimetric calculations were done with OLINDA/EXM software using mono-exponential time activity curve fitting. Results: the mean radiation dose for kidneys (67-208 cm3) in one cycle was 2.9 Gy (0,48 mGy/MBq) range 0.8-7.7 Gy using kidney volumetric analysis and 4.8 Gy (0.80 mGy/MBq) range 1.3-15.4 Gy using small volume analysis. 20 patients received four cycles. In this group radiation dose to the kidneys in the first cycle was 2.8 Gy (range 1.0-5.3 Gy) in second 2.5 Gy (range 0.7-3.9 Gy), in third 3.2 Gy (range 1.3-6.4 Gy) and in fourth cycle 3.2 Gy (range 1.5-7.7 Gy). Small volume technique yielded 1.7 times (range 1.0-2.2) higher radiation doses compared with volumetric analysis. The cumulative administered doses in 4 cycle treatments were 14.0-29.3 GBq. The effective half live for kidneys was 45 h (range 30-110 h). The highest kidney dose was 20,5 Gy and this patient received

  14. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    International Nuclear Information System (INIS)

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m2) on day 1 and oral Etoposide (50 mg/m2/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor

  15. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  16. Efeito da altura do selim na cinemática da lombar de ciclistas Effect of saddle height on the kinematics of lumbar spine of cyclists

    Directory of Open Access Journals (Sweden)

    Julio Francisco Kleinpaul

    2012-12-01

    Full Text Available O objetivo deste estudo foi analisar a influência da altura do selim sobre a cinemática da coluna lombar durante o ciclismo. Foram avaliados oito ciclistas recreacionais, na situação usual (auto ajustada e na situação de selim ajustado, com carga de 150 W, utilizando-se avaliação cinemática bidimensional em um ciclosimulador. Foram mensurados os ângulos de flexão, inclinação lateral e rotação da coluna lombar. A flexão da lombar foi maior na situação de selim ajustado, enquanto que a inclinação e a rotação da lombar foram maiores na situação de ajuste usual. Quanto ao comportamento ao longo do ciclo de pedalada, ocorreram dois ciclos de flexão-extensão durante um ciclo completo do pé-de-vela, e apenas um ciclo de inclinação lateral ou de rotação. As maiores diferenças acorreram no início, meio e fim do ciclo. O ajuste equivocado do selim não acarreta alterações na cinemática da coluna lombar.The aim of this study was to analyze the influence of saddle height on the kinematics of the lumbar spine during cycling. Eight recreational cyclists were assessed in an usual situation (self-selected and the situation of saddle properly adjusted while pedaling with a load set at 150 W. Using two-dimensional kinematic the angles of flexion, lateral inclination and rotation of the lumbar spine were computed. The flexion was greater in the adjusted position whereas the highest average tilt and rotation angles occurred in the usual position. There were two cycles of flexion-extension observed during a complete pedaling cycle, and only one cycle of lateral inclination and rotation. The major differences were observed at early, middle and end of the pedaling cycle. The mismanagement of the saddle did not involve significant changes in the kinematics of the lumbar spine for the conditions tested.

  17. Evaluation of a process for the decontamination of radioactive hotspots due to activated stellite particles

    International Nuclear Information System (INIS)

    Some of the Indian PHWRs which used stellite balls in the ball and screw mechanism of the adjustor rod drive mechanism in the moderator circuit encountered high radiation field in moderator system due to 60Co. Release of particulate stellite was responsible for the hotspots besides the general uniform contamination of internal surfaces with 60Co. Extensive laboratory studies have shown that it is possible to dissolve these stellite particles by adopting a three step redox process with permanganic acid as the oxidizing agent. These investigations with inactive stellite in powder form helped to optimize the process conditions. Permanganic acid was found to have the highest dissolution efficiency as compared to alkaline and nitric acid permanganate. The concentration of the permanganate was also found to be an important factor in deciding the efficiency of the dissolution of stellite. The efficiency of dissolution as a function of permanganic acid concentration showed a maximum. This process was evaluated for its effectiveness on components from nuclear power plants. Component decontamination was carried out on adjustor rod drive assemblies which had 60Co activity due to stellite particles with the radiation field ranging from 3 R/h to 20 R/h. They were subjected to decontamination with permanganic acid as oxidizing agent, followed by citric acid and a solution containing EDTA, ascorbic acid and citric acid in 4:3:3 ratio by weight (EAC) as reducing formulations. A test rig was fabricated for this purpose. In the first trial, one adjustor rod drive mechanism was subjected to decontamination. After two cycles of treatment, an average decontamination factor (DF) of 6.8, with a maximum DF of 11.7 was achieved. The same process but one cycle was repeated on eight more adjustor rod drive mechanisms. 60Co activity in the range of 13 - 93 mCi was removed from these adjustor rods. Loose contamination of the order of 30000 - 40000 dpm/cm2 observed before decontamination got

  18. Evaluation of a process for the decontamination of radioactive hotspots due to activated stellite particles

    International Nuclear Information System (INIS)

    Some of the Indian pressurized heavy water reactors (PHWRs) which use Stellite balls in the ball and screw mechanism of the adjustor rod drive mechanism in the moderator circuit have encountered high radiation fields in the moderator system due to 60Co. Release of particulate Stellite is responsible for the hotspots in addition to the general uniform contamination of internal surfaces with 60Co. Extensive laboratory studies have shown that it is possible to dissolve these Stellite particles by adopting a three-step redox process with permanganic acid as the oxidizing agent. These investigations with inactive Stellite in powder form helped to optimize the process conditions. Permanganic acid was found to have the highest dissolution efficiency as compared to alkaline and nitric acid permanganate. The susceptibility of Stellite to corrode or dissolve was found to depend on the concentration of the permanganate, pH and temperature of the process and microstructure of the Stellite alloy. This process was evaluated for its effectiveness on components from nuclear power plants. Component decontamination was carried out on adjustor rod drive assemblies which had 60Co activity due to Stellite particles with the radiation field ranging from 3 R . h-1 to 20 R . h-1. They were subjected to decontamination with permanganic acid as the oxidizing agent, followed by citric acid and a solution containing ethylenediaminetetraacetic acid, ascorbic acid and citric acid in a 4:3:3 ratio by weight as the reducing formulation. In the first trial, one adjustor rod drive mechanism was subjected to decontamination. After two cycles of treatment, an average decontamination factor (DF) of 6.8, with a maximum DF of 11.7, was achieved. The same process but with one cycle was repeated on eight more adjustor rod drive mechanisms. 60Co activity in the range of 13-93 mCi was removed from these adjustor rods. Loose contamination of the order of 30 000-40 000 decays per min and cm2 observed before

  19. Robust multi-tissue gene panel for cancer detection

    Directory of Open Access Journals (Sweden)

    Talantov Dmitri

    2010-06-01

    Full Text Available Abstract Background We have identified a set of genes whose relative mRNA expression levels in various solid tumors can be used to robustly distinguish cancer from matching normal tissue. Our current feature set consists of 113 gene probes for 104 unique genes, originally identified as differentially expressed in solid primary tumors in microarray data on Affymetrix HG-U133A platform in five tissue types: breast, colon, lung, prostate and ovary. For each dataset, we first identified a set of genes significantly differentially expressed in tumor vs. normal tissue at p-value = 0.05 using an experimentally derived error model. Our common cancer gene panel is the intersection of these sets of significantly dysregulated genes and can distinguish tumors from normal tissue on all these five tissue types. Methods Frozen tumor specimens were obtained from two commercial vendors Clinomics (Pittsfield, MA and Asterand (Detroit, MI. Biotinylated targets were prepared using published methods (Affymetrix, CA and hybridized to Affymetrix U133A GeneChips (Affymetrix, CA. Expression values for each gene were calculated using Affymetrix GeneChip analysis software MAS 5.0. We then used a software package called Genes@Work for differential expression discovery, and SVM light linear kernel for building classification models. Results We validate the predictability of this gene list on several publicly available data sets generated on the same platform. Of note, when analysing the lung cancer data set of Spira et al, using an SVM linear kernel classifier, our gene panel had 94.7% leave-one-out accuracy compared to 87.8% using the gene panel in the original paper. In addition, we performed high-throughput validation on the Dana Farber Cancer Institute GCOD database and several GEO datasets. Conclusions Our result showed the potential for this panel as a robust classification tool for multiple tumor types on the Affymetrix platform, as well as other whole genome arrays

  20. Evaluation of Microarray Preprocessing Algorithms Based on Concordance with RT-PCR in Clinical Samples

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Szallasi, Zoltan Imre; Eklund, Aron Charles; Gyorffy, B; Molnar, B

    2009-01-01

    Several preprocessing algorithms for Affymetrix gene expression microarrays have been developed, and their performance on spike-in data sets has been evaluated previously. However, a comprehensive comparison of preprocessing algorithms on samples taken under research conditions has not been...... performed. METHODOLOGY/PRINCIPAL FINDINGS: We used TaqMan RT-PCR arrays as a reference to evaluate the accuracy of expression values from Affymetrix microarrays in two experimental data sets: one comprising 84 genes in 36 colon biopsies, and the other comprising 75 genes in 29 cancer cell lines. We...... evaluated consistency using the Pearson correlation between measurements obtained on the two platforms. Also, we introduce the log-ratio discrepancy as a more relevant measure of discordance between gene expression platforms. Of nine preprocessing algorithms tested, PLIER+16 produced expression values that...

  1. ROBO1 deletion as a novel germline alteration in breast and colorectal cancer patients

    DEFF Research Database (Denmark)

    Villacis, Rolando A R; Abreu, Francine B; Miranda, Priscila M; Domingues, Maria A C; Carraro, Dirce M; Santos, Erika M M; Andrade, Victor P; Rossi, Benedito M; Achatz, Maria I; Rogatto, Silvia R

    2016-01-01

    interrogated in 113 unrelated cases fulfilling the criteria for hereditary BC/CRC and presenting non-pathogenic mutations in BRCA1, BRCA2, MLH1, MSH2, TP53, and CHEK2 genes. An identical germline deep intronic deletion of ROBO1 was identified in three index patients using two microarray platforms (Agilent 4x......180K and Affymetrix CytoScan HD). The ROBO1 deletion was confirmed by quantitative PCR (qPCR). Six relatives were also evaluated by CytoScan HD Array. Genomic analysis confirmed a co-segregation of the ROBO1 deletion with the occurrence of cancer in two families. Direct sequencing revealed no...... pathogenic ROBO1 point mutations. Transcriptomic analysis (HTA 2.0, Affymetrix) in two breast carcinomas from a single patient revealed ROBO1 down-expression with no splicing events near the intronic deletion. Deeper in silico analysis showed several enhancer regions and a histone methylation mark in the...

  2. Changes in skeletal muscle gene expression following clenbuterol administration

    OpenAIRE

    McIntyre Lauren M; McDaneld Tara G; Spurlock Diane M

    2006-01-01

    Abstract Background Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administ...

  3. Barley grain maturation and germination: Metabolic pathway and regulatory network commonalities and differences highlighted by new MapMan/PageMan profiling tools

    OpenAIRE

    Sreenivasulu, N.; Usadel, B.; Winter, A.; Radchuk, V.; Scholz, U.; Stein, N.; Weschke, W.; Strickert, M.; Close, T; Stitt, M.; Graner, A; Wobus, U

    2008-01-01

    Plant seeds prepare for germination already during seed maturation. We performed a detailed transcriptome analysis of barley (Hordeum vulgare) grain maturation, desiccation, and germination in two tissue fractions (starchy endosperm / aleurone and embryo / scutellum) using the Affymetrix Barley1 GeneChip. To aid data evaluation, Arabidopsis thaliana MapMan and PageMan tools were adapted to barley. The analyses allow a number of conclusions: (1) Cluster analysis revealed a smooth transition in...

  4. p53 Mutation analysis in breast tumors by a DNA microarray method.

    Science.gov (United States)

    Tennis, Meredith; Krishnan, Shiva; Bonner, Matthew; Ambrosone, Christine B; Vena, John E; Moysich, Kirsten; Swede, Helen; McCann, Susan; Hall, Per; Shields, Peter G; Freudenheim, Jo L

    2006-01-01

    The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study. PMID:16434591

  5. Development of a high density 600K SNP genotyping array for chicken

    OpenAIRE

    Kranis, Andreas; Gheyas, Almas A; Boschiero, Clarissa; Turner, Frances; Yu, Le; Smith, Sarah; Talbot, Richard; Pirani, Ali; Brew, Fiona; Kaiser, Pete; Hocking, Paul M.; Fife, Mark; Salmon, Nigel; Fulton, Janet; Strom, Tim M

    2013-01-01

    Background High density (HD) SNP genotyping arrays are an important tool for genetic analyses of animals and plants. Although the chicken is one of the most important farm animals, no HD array is yet available for high resolution genetic analysis of this species. Results We report here the development of a 600 K Affymetrix® Axiom® HD genotyping array designed using SNPs segregating in a wide variety of chicken populations. In order to generate a large catalogue of segregating SNPs, ...

  6. Differential co-expression analysis of obesity-associated networks in human subcutaneous adipose tissue

    OpenAIRE

    Walley, A J; Jacobson, P.; Falchi, M.; Bottolo, L.; Andersson, J.C.; Petretto, E; Bonnefond, A.; Vaillant, E; Lecoeur, C; Vatin, V.; Jernas, M; Balding, D; Petteni, M.; Park, Y S; Aitman, T

    2011-01-01

    Objective To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping, and a co-expression regulatory network approach in subcutaneous human adipose tissue to identify genes relevant to the obese state. Study design Genome-wide transcript expression in subcutaneous human adipose tissue was measured using Affymetrix U133+2.0 microarrays and genomewide genotyping data was obtained using an Applied Biosy...

  7. Glycolipid and Ganglioside Metabolism Imbalances In Huntington’s Disease

    OpenAIRE

    Desplats, Paula A.; Denny, Christine. A.; Kass, Kristi E.; Gilmartin, Tim; Head, Steven R.; Sutcliffe, J. Gregor; Seyfried, Thomas N; Thomas, Elizabeth A.

    2007-01-01

    We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington’s disease (HD) mice using a custom designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD patients. Many of these genes show differential regional expression within the CNS, as indicated ...

  8. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

    OpenAIRE

    Jingsong Shi; Song Jiang; Dandan Qiu; Weibo Le; Xiao Wang; Yinhui Lu; Zhihong Liu

    2016-01-01

    Objective. To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profiles and the Connectivity Map (CMAP). Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs) between late stage and early stage DN samples and the CMAP database were used to identify pote...

  9. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase

    OpenAIRE

    Wright, Gary L.; Maroulakou, Ioanna G.; Eldridge, Juanita; Liby, Tiera L.; Sridharan, Vijayalakshmi; Tsichlis, Philip N.; Muise-Helmericks, Robin C.

    2008-01-01

    The growth factor, vascular endothelial growth factor (VEGF), induces angiogenesis and promotes endothelial cell (EC) proliferation. Affymetrix gene array analyses show that VEGF stimulates the expression of a cluster of nuclear-encoded mitochondrial genes, suggesting a role for VEGF in the regulation of mitochondrial biogenesis. We show that the serine threonine kinase Akt3 specifically links VEGF to mitochondrial biogenesis. A direct comparison of Akt1 vs. Akt3 gene silencing was performed ...

  10. Facilitating functional annotation of chicken microarray data

    Directory of Open Access Journals (Sweden)

    Gresham Cathy R

    2009-10-01

    Full Text Available Abstract Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO. However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and

  11. Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

    OpenAIRE

    Cupples, L. Adrienne; D'Agostino, Ralph B.; Hwang, Shih-Jen; Ingellson, Erik; Liu, Chunyu; Murabito, Joanne M.; Polak, Joseph F.; Wolf, Philip A.; Demissie, Serkalem; O'Donnell, Christopher Joseph; Fox, Caroline; Hoffmann, Udo

    2007-01-01

    Introduction: Subclinical atherosclerosis (SCA) measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study. Methods: Over 100,000 single nucleotide polymorphisms (SNPs) were genotyped (Human 100K GeneChip, Affymetrix) in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and multiva...

  12. Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study

    OpenAIRE

    Hwang Shih-Jen; Hoffmann Udo; Fox Caroline S; D'Agostino Ralph B; Cupples L Adrienne; O'Donnell Christopher J; Ingellson Erik; Liu Chunyu; Murabito Joanne M; Polak Joseph F; Wolf Philip A; Demissie Serkalem

    2007-01-01

    Abstract Introduction Subclinical atherosclerosis (SCA) measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study. Methods Over 100,000 single nucleotide polymorphisms (SNPs) were genotyped (Human 100K GeneChip, Affymetrix) in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and ...

  13. Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

    OpenAIRE

    Middelbos, Ingmar S.; Brittany M Vester; Lisa K Karr-Lilienthal; Schook, Lawrence B; Swanson, Kelly S.

    2009-01-01

    We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridiz...

  14. Entwicklung und Vergleich biostatistischer Methoden zur Auswertung von Microarray Experimenten

    OpenAIRE

    Clevert, Djork-Arné

    2012-01-01

    Motivation: Cost-effective oligonucleotide arrays like the Affymetrix SNP 6.0 and the Human Gene 1.1 ST are still the predominant technique to measure DNA copy number variations (CNVs) and gene expression, respectively. However, microarray data are characterized by high levels of noise induced by DNA preparation, staining, hybridization or measurement processes. This obscuring variation can blur out the signal of interest and, even worse, lead to spurious correlations which misguide the resea...

  15. Further statistical analysis for genome-wide expression evolution in primate brain/liver/fibroblast tissue

    OpenAIRE

    Gu Jianying; Gu Xun

    2004-01-01

    Abstract In spite of only a 1-2 per cent genomic DNA sequence difference, humans and chimpanzees differ considerably in behaviour and cognition. Affymetrix microarray technology provides a novel approach to addressing a long-term debate on whether the difference between humans and chimpanzees results from the alteration of gene expressions. Here, we used several statistical methods (distance method, two-sample t-tests, regularised t-tests, ANOVA and bootstrapping) to detect the differential e...

  16. Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease

    OpenAIRE

    Collison, Kate S; Maqbool, Zakia; Saleh, Soad M; Inglis, Angela; Makhoul, Nadine J; Bakheet, Razan; Al-Johi, Mohammed; Al-Rabiah, Rana; Zaidi, Marya Z; Al-Mohanna, Futwan A.

    2009-01-01

    The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepat...

  17. Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

    OpenAIRE

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer,; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall,; Marshall, Christian

    2007-01-01

    Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analys...

  18. Case-control genome-wide association study of attention-deficit/hyperactivity disorder

    OpenAIRE

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard JL; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark

    2010-01-01

    Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotvped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affy...

  19. A Comparative Study of Genome-Wide Transcriptional Profiles of Primary Hepatocytes in Collagen Sandwich and Monolayer Cultures

    OpenAIRE

    Kim, Yeonhee; Lasher, Christopher D; Milford, Logan M.; Murali, T.M.; Rajagopalan, Padmavathy

    2010-01-01

    Two commonly used culture systems in hepatic tissue engineering are the collagen sandwich (CS) and monolayers of cells. In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and compared via gene set enrichment analysis to elicit biologically meaningful information at the level of gene sets. Our results demonstrate that gene expression in hepatocytes in CS cultures steadily and comp...

  20. ExonMiner: Web service for analysis of GeneChip Exon array data

    OpenAIRE

    Imoto Seiya; Saito Ayumu; Nagasaki Masao; Yoshida Ryo; Numata Kazuyuki; Miyano Satoru

    2008-01-01

    Abstract Background Some splicing isoform-specific transcriptional regulations are related to disease. Therefore, detection of disease specific splice variations is the first step for finding disease specific transcriptional regulations. Affymetrix Human Exon 1.0 ST Array can measure exon-level expression profiles that are suitable to find differentially expressed exons in genome-wide scale. However, exon array produces massive datasets that are more than we can handle and analyze on personal...

  1. AffyMiner: mining differentially expressed genes and biological knowledge in GeneChip microarray data

    OpenAIRE

    Xia Yuannan; Nguyen The V; Lu Guoqing; Fromm Michael

    2006-01-01

    Abstract Background DNA microarrays are a powerful tool for monitoring the expression of tens of thousands of genes simultaneously. With the advance of microarray technology, the challenge issue becomes how to analyze a large amount of microarray data and make biological sense of them. Affymetrix GeneChips are widely used microarrays, where a variety of statistical algorithms have been explored and used for detecting significant genes in the experiment. These methods rely solely on the quanti...

  2. Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

    OpenAIRE

    Skoog Lambert; Shaw Peter; Pawitan Yudi; Nordgren Hans; Miller Lance D; Liu Edison T; Lin Chin-Yo; Huang Fei; Bjöhle Judith; Ploner Alexander; Hall Per; Smeds Johanna; Wedrén Sara; Öhd John; Bergh Jonas

    2006-01-01

    Abstract Background Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results HRT use in patients with estrogen receptor (ER) pr...

  3. Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction

    OpenAIRE

    Ahmed, Serge H.; Lutjens, Robert; van der Stap, Lena D.; Lekic, Dusan; Romano-Spica, Vincenzo; Morales, Marisela; Koob, George F.; Repunte-Canonigo, Vez; Sanna, Pietro Paolo

    2005-01-01

    By using high-density oligonucleotide arrays, we profiled gene expression in reward-related brain regions of rats that developed escalated cocaine intake after extended access to cocaine (6 h per day). Rats allowed restricted daily access to cocaine (only 1 h) that displayed a stable level of cocaine intake and cocaine naive rats were used for controls. Four analysis methods were compared: Affymetrix microarray suite 4 and microarray suite 5, which use perfect-match-minus-mismatch models, and...

  4. Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin

    OpenAIRE

    ALBERTSON, DAWN N.; Pruetz, Barb; Schmidt, Carl J.; KUHN, DONALD M.; Kapatos, Gregory; Bannon, Michael J.

    2004-01-01

    Chronic cocaine abuse induces long-term neural adaptations as a consequence of alterations in gene expression. This study was undertaken to identify those transcripts differentially regulated in the nucleus accumbens of human cocaine abusers. Affymetrix microarrays were used to measure transcript abundance in 10 cocaine abusers and 10 control subjects matched for age, race, sex, and brain pH. As expected, gene expression of cocaine- and amphetamine-regulated transcript (CART) was increased in...

  5. Distinctive Profiles of Gene Expression in the Human Nucleus Accumbens Associated with Cocaine and Heroin Abuse

    OpenAIRE

    ALBERTSON, DAWN N.; Schmidt, Carl J.; Kapatos, Gregory; Bannon, Michael J.

    2006-01-01

    Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized highthroughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involvi...

  6. Gene Expression Profiling in the Brains of Human Cocaine Abusers

    OpenAIRE

    Bannon, Michael J.; Kapatos, Gregory; ALBERTSON, DAWN N.

    2005-01-01

    Chronic cocaine abuse induces long-term neurochemical, structural and behavioural changes thought to result from altered gene expression within the nucleus accumbens and other brain regions playing a critical role in addiction. Recent methodological advances now allow the profiling of gene expression in human postmortem brain. In this article, we review studies in which we have used Affymetrix oligonucleotide microarrays to identify transcripts that are differentially expressed in the nucleus...

  7. Transcriptomic Profile Reveals Gender-Specific Molecular Mechanisms Driving Multiple Sclerosis Progression

    OpenAIRE

    Irizar, Haritz; Muñoz-Culla, Maider; Sepúlveda, Lucia; Sáenz-Cuesta, Matías; Prada, Álvaro; Castillo-Triviño, Tamara; Zamora-López, Gorka; de Munain, Adolfo López; Olascoaga, Javier; Otaegui, David

    2014-01-01

    Background Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients. Results The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy...

  8. Polygenic Transmission and Complex Neuro developmental Network for Attention Deficit Hyperactivity Disorder: Genome-Wide Association Study of Both Common and Rare Variants

    OpenAIRE

    Yang, Li; et al

    2013-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK....

  9. Transcription profiling by array of Arabidopsis thaliana wild type (Col-0) and flowering time mutants to investigate synchronized induction of flowering

    OpenAIRE

    Valentim, F.L.; Mourik, van, J.A.; Posé, D.; Kim, M.C.; M. Schmid; van der Ham; Busscher, M.; Sanchez-Perez, G.F.; Molenaar, J.; Immink, G.H.; Dijk, van, G.

    2013-01-01

    Synchronized induction of flowering in Arabidopsis thaliana wild type (Col-0) and flowering time mutants (soc1, agl24, fd) by shifting from short day (8 hr light, 16 hr dark; 23C; 65% rel humidity) to long day (16 hr light, 8 hr dark; 23C; 65% rel humidity) for 0, 3, 5, and 7 days. Biotinylated probes were synthesized from RNA isolated from manually disseted shoot meristems and hybridized to Affymetrix ATH1 arrays.

  10. Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization

    OpenAIRE

    Li H Irene; Lemyre Emmanuelle; Langlois Sylvie; Gibson William T; Flibotte Stephane; Delaney Allen D; Chai David; Chan Susanna; Boerkoel Cornelius; Birch Patricia; Baross Agnes; Armstrong Linlea; Arbour Laura; Adam Shelin; Friedman JM

    2009-01-01

    Abstract Background Array genomic hybridization is being used clinically to detect pathogenic copy number variants in children with intellectual disability and other birth defects. However, there is no agreement regarding the kind of array, the distribution of probes across the genome, or the resolution that is most appropriate for clinical use. Results We performed 500 K Affymetrix GeneChip® array genomic hybridization in 100 idiopathic intellectual disability trios, each comprised of a chil...

  11. A comprehensive transcriptomic view of renal function in the malaria vector, Anopheles gambiae

    DEFF Research Database (Denmark)

    Overend, Gayle; Cabrero, Pablo; Halberg, Kenneth Agerlin;

    2015-01-01

    Renal function is essential to maintain homeostasis. This is particularly significant for insects that undergo complete metamorphosis; larval mosquitoes must survive a freshwater habitat whereas adults are terrestrial, and mature females must maintain ion and fluid homeostasis after blood feeding....... To investigate the physiological adaptations required for successful development to adulthood, we studied the Malpighian tubule transcriptome of Anopheles gambiae using Affymetrix arrays. We assessed transcription under several conditions; as third instar larvae, as adult males fed on sugar, as adult...

  12. Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis

    OpenAIRE

    Holger G Hass, Oliver Nehls, Juergen Jobst, Andrea Frilling, Ulrich Vogel, Stephan Kaiser

    2008-01-01

    AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.METHODS: Oligonucleotide arrays (Affymetrix U133A) were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding non-malignant liver tissue. To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 pro...

  13. Mining large collections of gene expression data to elucidate transcriptional regulation of biological processes

    OpenAIRE

    Curry, Edward William James

    2011-01-01

    A vast amount of gene expression data is available to biological researchers. As of October 2010, the GEO database has 45,777 chips of publicly available gene expression pro ling data from the Affymetrix (HGU133v2) GeneChip platform, representing 2.5 billion numerical measurements. Given this wealth of data, `meta-analysis' methods allowing inferences to be made from combinations of samples from different experiments are critically important. This thesis explores the applicatio...

  14. Down-regulation of the Fetal Stem Cell Factor SOX17 by H33342: A MECHANISM RESPONSIBLE FOR DIFFERENTIAL GENE EXPRESSION IN BREAST CANCER SIDE POPULATION CELLS

    OpenAIRE

    Christgen, Matthias; Geffers, Robert; Ballmaier, Matthias; Christgen, Henriette; Poczkaj, Janette; Krech, Till; Kreipe, Hans; Lehmann, Ulrich

    2009-01-01

    Human solid tumors contain rare cancer side population (SP) cells, which expel the fluorescent dye Hoechst 33342 (H33342) and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays and quantitative reverse transcription-PCR, we investigated differential gene expression between S...

  15. Soybean Knowledge Base (SoyKB): a web resource for soybean translational genomics

    OpenAIRE

    2012-01-01

    Background Soybean Knowledge Base (SoyKB) is a comprehensive all-inclusive web resource for soybean translational genomics. SoyKB is designed to handle the management and integration of soybean genomics, transcriptomics, proteomics and metabolomics data along with annotation of gene function and biological pathway. It contains information on four entities, namely genes, microRNAs, metabolites and single nucleotide polymorphisms (SNPs). Methods SoyKB has many useful tools such as Affymetrix pr...

  16. Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

    OpenAIRE

    Faner, Rosa; Gonzalez, Nuria; Cruz, Tamara; Kalko, Susana Graciela; Agustí, Alvar

    2014-01-01

    Background Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly. Methods We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry. We also ...

  17. Comparative transcriptional profiling of orange fruit in response to the biocontrol yeast Kloeckera apiculata and its active compounds

    OpenAIRE

    Liu, Pu; Chen, Kai; Li, Guofeng; Yang, Xiaoping; Long, Chao-an

    2016-01-01

    Background The yeast Kloeckera apiculata strain 34–9 is an antagonist that shows biological control activity against the postharvest fungal pathogens of citrus. An antifungal compound, 2-phenylethanol (PEA), has been identified from the extract of K. apiculata. To better understand the molecular processes underlying the response of citrus fruit tissue to K. apiculata, the extract and PEA, microarray analyses were performed on navel oranges using an Affymetrix Citrus GeneChip. Results As many ...

  18. Gene expression profiling of taxol-resistant nasopharyngeal carcinoma cells with siRNA-mediated FOLR1 downregulation

    OpenAIRE

    Song, Yexun; Peng, Xiaowei; Wang, Min; Xie, Jun; Tan, Guolin

    2015-01-01

    Objectives: Our previous study has shown that downregulation of FOLR1 by siRNA partially reversed taxol-resistant phenotype in taxol-resistant nasopharyngeal carcinoma cell lines. We aim to gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes after FOLR1 downregulation. Method: The global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array. Results: There was a significant dysregulation i...

  19. Clinical and Biological Implications of MYC Activation: A common difference between MGUS and newly diagnosed multiple myeloma

    OpenAIRE

    Chng, WJ; Huang, GF; Chung, TH; Ng, SB; Gonzalez-Paz, N; Troska-Price, T; Mulligan, G.; Chesi, M; Bergsagel, PL; Fonseca, R.

    2011-01-01

    Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed a gene expression datasets generated on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes over-expressed in MM were enriched for cell cycle, proliferation and MYC activation gene-sets. Upon dissecting the relationship between MYC and cell cycle genesets, we identified and validat...

  20. Identification of Reference Genes across Physiological States for qRT-PCR through Microarray Meta-Analysis

    OpenAIRE

    Cheng, Wei-Chung; Chang, Cheng-Wei; Chen, Chaang-Ray; Tsai, Min-Lung; Shu, Wun-Yi; Li, Chia-Yang; Hsu, Ian C.

    2011-01-01

    Background The accuracy of quantitative real-time PCR (qRT-PCR) is highly dependent on reliable reference gene(s). Some housekeeping genes which are commonly used for normalization are widely recognized as inappropriate in many experimental conditions. This study aimed to identify reference genes for clinical studies through microarray meta-analysis of human clinical samples. Methodology/Principal Findings After uniform data preprocessing and data quality control, 4,804 Affymetrix HU-133A arr...

  1. The removal of multiplicative, systematic bias allows integration of breast cancer gene expression datasets - improving meta-analysis and prediction of prognosis

    OpenAIRE

    Pepper Stuart D; Okoniewski Michal J; Hey Yvonne; Smethurst Graeme J; Sims Andrew H; Howell Anthony; Miller Crispin J; Clarke Robert B

    2008-01-01

    Abstract Background The number of gene expression studies in the public domain is rapidly increasing, representing a highly valuable resource. However, dataset-specific bias precludes meta-analysis at the raw transcript level, even when the RNA is from comparable sources and has been processed on the same microarray platform using similar protocols. Here, we demonstrate, using Affymetrix data, that much of this bias can be removed, allowing multiple datasets to be legitimately combined for me...

  2. Dysfunctional Activation of Neurotensin/IL-8 Pathway in Hepatocellular Carcinoma Is Associated with Increased Inflammatory Response in Microenvironment, More Epithelial Mesenchymal Transition in Cancer and Worse Prognosis in Patients

    OpenAIRE

    Yu, Jinpu; Ren, Xiubao; Chen, Yongzi; Liu, Pengpeng; Wei, Xiyin; Li, Hui; Ying, GuoGuang; Chen, Kexin; WINKLER, HANS; Hao, Xishan

    2013-01-01

    Aim To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. Methods The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different...

  3. Transcriptional profiling of Medicago truncatula meristematic root cells

    OpenAIRE

    Rolfe Barry G; Weiller Georg F; Goffard Nicolas; Holmes Peta; Imin Nijat

    2008-01-01

    Abstract Background The root apical meristem of crop and model legume Medicago truncatula is a significantly different stem cell system to that of the widely studied model plant species Arabidopsis thaliana. In this study we used the Affymetrix Medicago GeneChip® to compare the transcriptomes of meristem and non-meristematic root to identify root meristem specific candidate genes. Results Using mRNA from root meristem and non-meristem we were able to identify 324 and 363 transcripts different...

  4. Transcriptional profiling of Medicago truncatula meristematic root cells

    OpenAIRE

    Holmes, Peta; Goffard, Nicolas; Weiller, Georg F; Rolfe, Barry G.; Imin, Nijat

    2008-01-01

    Background The root apical meristem of crop and model legume Medicago truncatula is a significantly different stem cell system to that of the widely studied model plant species Arabidopsis thaliana. In this study we used the Affymetrix Medicago GeneChip® to compare the transcriptomes of meristem and non-meristematic root to identify root meristem specific candidate genes. Results Using mRNA from root meristem and non-meristem we were able to identify 324 and 363 transcripts differentially exp...

  5. Chromosomal microarrays testing in children with developmental disabilities and congenital anomalies

    OpenAIRE

    Guillermo Lay-Son; Karena Espinoza; Cecilia Vial; Juan C. Rivera; María L. Guzmán; GABRIELA M REPETTO

    2015-01-01

    OBJECTIVES: Clinical use of microarray-based techniques for the analysis of many developmental disorders has emerged during the last decade. Thus, chromosomal microarray has been positioned as a first-tier test. This study reports the first experience in a Chilean cohort. METHODS: Chilean patients with developmental disabilities and congenital anomalies were studied with a high-density microarray (CytoScan(tm) HD Array, Affymetrix, Inc., Santa Clara, CA, USA). Patients had previous cytogeneti...

  6. Peripheral blood gene expression profiles in COPD subjects

    OpenAIRE

    2011-01-01

    To identify non-invasive gene expression markers for chronic obstructive pulmonary disease (COPD), we performed genome-wide expression profiling of peripheral blood samples from 12 subjects with significant airflow obstruction and an equal number of non-obstructed controls. RNA was isolated from Peripheral Blood Mononuclear Cells (PBMCs) and gene expression was assessed using Affymetrix U133 Plus 2.0 arrays. Tests for gene expression changes that discriminate between COPD cases (FEV1< 70% pre...

  7. Negative energy balance alters global gene expression and immune responses in the uterus of postpartum dairy cows

    OpenAIRE

    Wathes, D Claire; Cheng, Zhangrui; Chowdhury, Waliul; Fenwick, Mark A.; Fitzpatrick, Richard; Morris, Dermot G; Patton, Joe; Murphy, John J.

    2009-01-01

    Most dairy cows suffer uterine microbial contamination postpartum. Persistent endometritis often develops, associated with reduced fertility. We used a model of differential feeding and milking regimes to produce cows in differing negative energy balance status in early lactation (mild or severe, MNEB or SNEB). Blood hematology was assessed preslaughter at 2 wk postpartum. RNA expression in endometrial samples was compared using bovine Affymetrix arrays. Data were mapped using Ingenuity Pathw...

  8. Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis

    OpenAIRE

    de Bont, Judith M.; Kros, Johan M.; Passier, Monique M.C.J.; Reddingius, Roel E.; Sillevis Smitt, Peter A.E.; Luider, Theo M.; Den Boer, Monique L.; Pieters, Rob

    2008-01-01

    The objective of this study was to identify differentially expressed and prognostically important genes in pediatric medulloblastoma and pediatric ependymoma by Affymetrix microarray analysis. Among the most discriminative genes, three members of the SOX transcription factor family were differentially expressed. Both SOX4 and SOX11 were significantly overexpressed in medulloblastoma (median, 11-fold and 5-fold, respectively) compared with ependymoma and normal cerebellum. SOX9 had greater exp...

  9. Mechano-Regulation of Alternative Splicing

    OpenAIRE

    Liu, Huan; Tang, Liling

    2013-01-01

    Alternative splicing contributes to the complexity of proteome by producing multiple mRNAs from a single gene. Affymetrix exon arrays and experiments in vivo or in vitro demonstrated that alternative splicing was regulated by mechanical stress. Expression of mechano-growth factor (MGF) which is the splicing isoform of insulin-like growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) splicing variants such as VEGF121, VEGF165, VEGF206, VEGF189, VEGF165 and VEGF145 are regulated...

  10. Different Transcriptional Response to Xanthomonas citri subsp. citri between Kumquat and Sweet Orange with Contrasting Canker Tolerance

    OpenAIRE

    Xing-Zheng Fu; Xiao-Qing Gong; Yue-Xin Zhang; Yin Wang; Ji-Hong Liu

    2012-01-01

    Citrus canker disease caused by Xanthomonas citri subsp. citri (Xcc) is one of the most devastating biotic stresses affecting the citrus industry. Meiwa kumquat (Fortunella crassifolia) is canker-resistant, while Newhall navel orange (Citrus sinensis Osbeck) is canker-sensitive. To understand the molecular mechanisms underlying the differences in responses to Xcc, transcriptomic profiles of these two genotypes following Xcc attack were compared by using the Affymetrix citrus genome GeneChip. ...

  11. Using expression arrays for copy number detection: an example from E. coli

    Directory of Open Access Journals (Sweden)

    Stitzer Michael E

    2007-06-01

    Full Text Available Abstract Background The sequencing of many genomes and tiling arrays consisting of millions of DNA segments spanning entire genomes have made high-resolution copy number analysis possible. Microarray-based comparative genomic hybridization (array CGH has enabled the high-resolution detection of DNA copy number aberrations. While many of the methods and algorithms developed for the analysis microarrays have focused on expression analysis, the same technology can be used to detect genetic alterations, using for example standard commercial Affymetrix arrays. Due to the nature of the resultant data, standard techniques for processing GeneChip expression experiments are inapplicable. Results We have developed a robust and flexible methodology for high-resolution analysis of DNA copy number of whole genomes, using Affymetrix high-density expression oligonucleotide microarrays. Copy number is obtained from fluorescence signals after processing with novel normalization, spatial artifact correction, data transformation and deletion/duplication detection. We applied our approach to identify deleted and amplified regions in E. coli mutants obtained after prolonged starvation. Conclusion The availability of Affymetrix expression chips for a wide variety of organisms makes the proposed array CGH methodology useful more generally.

  12. Molecular probe technology detects bacteria without culture

    Directory of Open Access Journals (Sweden)

    Hyman Richard W

    2012-03-01

    Full Text Available Abstract Background Our ultimate goal is to detect the entire human microbiome, in health and in disease, in a single reaction tube, and employing only commercially available reagents. To that end, we adapted molecular inversion probes to detect bacteria using solely a massively multiplex molecular technology. This molecular probe technology does not require growth of the bacteria in culture. Rather, the molecular probe technology requires only a sequence of forty sequential bases unique to the genome of the bacterium of interest. In this communication, we report the first results of employing our molecular probes to detect bacteria in clinical samples. Results While the assay on Affymetrix GenFlex Tag16K arrays allows the multiplexing of the detection of the bacteria in each clinical sample, one Affymetrix GenFlex Tag16K array must be used for each clinical sample. To multiplex the clinical samples, we introduce a second, independent assay for the molecular probes employing Sequencing by Oligonucleotide Ligation and Detection. By adding one unique oligonucleotide barcode for each clinical sample, we combine the samples after processing, but before sequencing, and sequence them together. Conclusions Overall, we have employed 192 molecular probes representing 40 bacteria to detect the bacteria in twenty-one vaginal swabs as assessed by the Affymetrix GenFlex Tag16K assay and fourteen of those by the Sequencing by Oligonucleotide Ligation and Detection assay. The correlations among the assays were excellent.

  13. Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes

    Directory of Open Access Journals (Sweden)

    Bihoreau Marie-Thérèse

    2009-02-01

    Full Text Available Abstract Background Microarray technologies are widely used to quantify the abundance of transcripts corresponding to thousands of genes. To maximise the robustness of transcriptome results, we have tested the performance and reproducibility of rat and mouse gene expression data obtained with Affymetrix, Illumina and Operon platforms. Results We present a thorough analysis of the degree of reproducibility provided by analysing the transcriptomic profile of the same animals of several experimental groups under different popular microarray technologies in different tissues. Concordant results from inter- and intra-platform comparisons were maximised by testing many popular computational methods for generating fold changes and significances and by only considering oligonucleotides giving high expression levels. The choice of Affymetrix signal extraction technique was shown to have the greatest effect on the concordance across platforms. In both species, when choosing optimal methods, the agreement between data generated on the Affymetrix and Illumina was excellent; this was verified using qRT-PCR on a selection of genes present on all platforms. Conclusion This study provides an extensive assessment of analytical methods best suited for processing data from different microarray technologies and can assist integration of technologically different gene expression datasets in biological systems.

  14. DEVELOPMENT OF BIOMASS OF ANIMAL AND VEGETABLE ORIGIN RECYCLING TECHNOLOGICAL LINE Разработка технологической линии утилизации биомасс животного и растительного происхождения

    Directory of Open Access Journals (Sweden)

    Vohmin V. S.

    2011-11-01

    Full Text Available The influence of stockbreeding complexes on hinterland is considered. The intensive way of animal breeding complex waste recycling in one cycle, as alternative energy source, is suggested

  15. 40 CFR 63.4364 - What are the requirements for CPMS installation, operation, and maintenance?

    Science.gov (United States)

    2010-07-01

    ... section. (1) Each CPMS must complete a minimum of one cycle of operation for each successive 15-minute... temperature sensor must be installed in the combustion chamber at a location in the combustion zone. (iii)...

  16. 40 CFR 60.1260 - What is the minimum amount of monitoring data I must collect with my continuous emission...

    Science.gov (United States)

    2010-07-01

    ... Performance for Small Municipal Waste Combustion Units for Which Construction is Commenced After August 30...) requires your continuous emission monitoring systems to complete at least one cycle of operation...

  17. 长春瑞滨联合卡培他滨对蒽环类和紫杉类药物耐药的晚期乳腺癌疗效观察%Vinorelbine combined with capecitabine for advanced breast cancer patients with anthracycline and taxane failure

    Institute of Scientific and Technical Information of China (English)

    徐正阳; 袁祖国; 周涛琪; 袁光波; 杨辉; 任瑞平

    2014-01-01

    目的观察长春瑞滨联合卡培他滨对蒽环类和紫杉类药物耐药的晚期乳腺癌患者的疗效和不良反应。方法32例晚期乳腺癌患者经长春瑞滨25mg/m2,静脉滴注,d1、8;卡培他滨2000mg/(m2·d),早晚2次,餐后30 min口服,d1~14,21d为1个周期,每例患者至少接受2个周期化疗或至疾病进展。结果32例患者共完成161个周期化疗,中位化疗5个周期。所有患者均可评价疗效和不良反应,其中完全缓解(CR)1例,部分缓解(PR)9例,疾病稳定(SD)13例,疾病进展(PD)9例。总有效率(CR+PR)31.2%,疾病控制率(DCR)71.9%,中位无进展生存期(TTP)8.3个月,1、2年生存率分别为66.9%和38.4%。不良反应主要为骨髓抑制、手足综合征及静脉炎,没有发生治疗相关性死亡。结论长春瑞滨联合卡培他滨方案是治疗对蒽环类和紫杉类药物耐药的晚期乳腺癌患者的有效方案,不良反应可以耐受。%Objective To evaluate the clinical efficacy and tolerance of vinorelbine with capecitabine for advanced breast cancer patients with anthracycline and taxane failure. Methods Thirty- two patients with anthracycline- and taxane- failure metastatic breast cancer were enrol ed in the study. Al patients were given 25mg/m2 of vinorelbine on d1 and d8, combined with 2 000mg/m2 of capecitabine daily from d1 to d14. The combined chemotherapy was repeated every 21d as one cycle. Patients received a minimal chemotherapy of two cycles or until disease progression. Results Al the 32 patients completed total 161 chemotherapy cycles with a median of 5 per patient. Adverse events and clinical efficacy were evaluated on all 32 patients. There were complete remission (CR) in 1 patient, partial remission (PR) in 9, stable disease (SD) in 13 and progression of disease (PD) in 9. The overal response rate (CR+PR) was 31.2%and the disease control rate (DCR) was 71.9%. The median time to progres

  18. Effects of Vinorelbine Combined with Xeloda in Anthracycline-and Taxane-pretreated Patients with Relapsed Metastatic Breast Cancer%长春瑞滨联合希罗达对蒽环类/紫杉类治疗后复发转移性乳腺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王楠; 代醒; 王留兴

    2013-01-01

    Objective To evaluate the short-term efficacy and adverse reactions of vinorelbine combined with xeloda to patients with recurrent and metastatic breast cancer after taxane and anthracycline treatment.Methods Forty patients with recurrent metastatic breast cancer after taxane and anthracycline treatment were recruited.Vinorelbine 25 mg/m2 on day 1 and day 8,eapecitabine 1 000 mg/m2,twice daily on day 1 to 14.Three weeks was one cycle.At least two cycles were given to each patient.Results Of the 40 patients,3 achieved CR,17 achieved PR,16 achieved SD,4 achieved PD,with a total response rate of 47.5%,with a clinical benefit response 70%.The median time to disease progression was 8.5 months.The common adverse reactions were myelosuppression,gastrointestinal reactions,hand-foot syndrome and neurotoxicity.Conclusion vinorelbine combined with capecitabine is an effective rigmens in the treatment of patients with relapsed and metastatic breast cancer,especially for those who have failed in chemotherapy with taxane and anthracycline.The therapy is well tolerated but has mild adverse reactions.%目的 探讨长春瑞滨联合希罗达方案对蒽环类/紫杉类治疗后晚期复发转移乳腺癌的近期疗效和不良反应.方法 40例应用蒽环类/紫杉类治疗后复发转移性乳腺癌患者,长春瑞滨25 mg/m2,静脉快速滴入,第1、8天;希罗达1 000 mg/m2,早晚两次餐后30 min口服,连用14天,21天为1周期,每例患者至少接受2周期的治疗.结果 40例患者完全缓解(CR)3例,部分缓解(PR) 16例,病情稳定(SD)14例,病情进展(PD)7例,总有效率47.5%,临床获益率为70%,中位疾病进展时间(TTP)为8.5月.常见不良反应为骨髓抑制、消化道反应、手足综合征、神经毒性,少数患者出现口腔炎、头晕、乏力和胸闷等.结论 长春瑞滨联合希罗达方案对紫杉/蒽环类治疗后复发转移乳腺癌疗效确切.治疗过程中患者耐受性好,不良反应轻.

  19. The Clinical Study of Docetaxel/Xeloda Combination in the Treatment of Advanced Breast Cancer%多西他赛联合卡培他滨治疗晚期乳腺癌疗效分析

    Institute of Scientific and Technical Information of China (English)

    田亚丽; 陶敏

    2011-01-01

    Objective To evaluate the safety and efficacy of Docetaxel/Xeloda combination chemotherapy for advanced breast cancer.Methods 38 patients with advanced breast cancer were treated with Docetaxel and Xeloda combination chemotherapy.Docetaxel 175mg/m2 ivgtt,d1 ;Xeloda was given at a dose of 1,000mg/m2/d,bid, A.C.for two weeks followed by one week rest as one cycle,at least for two cycle in each patient.Efficiency and toxicity were observed in everycycle.Results Among these 38 patients,there was 4 complete response.Rates of partial response 16,stable disease 13,progressive disease 5,and clinical benefit response (CR+PR)52.6%.Tumor control rate (CR+PR+SD) was 86.8%.The common adverse reactions were bone marrow suppression,gastrointestinal reactions and hand-foot syndrome.These adverse reactions can be tolerated,no treatment-related deaths in patients.Conclusion The combination of Docetaxel and Capecitabine is an effective regimen for patients with advanced breast cancer, and toxicities are tolerable to the majority of patients.It can be used as an effective rescue treatment of advanced breast cancer programs.%目的 研究多西他赛(Docetaxel)联合卡培他滨(Capecitabine/Xeloda)治疗晚期乳腺癌的疗效及可行性.方法 38例晚期乳腺癌患者均给予多西他赛75mg/m2,第1d;希罗达口服2次/d,餐后服用,每次1,000mg/m2,连续服用14d,治疗周期为21d,至少治疗2个周期.结果 该组完全缓解(CR)4例,部分缓解(PR)16例,稳定(SD)13例,疾病进展(PD)5例,总有效率(CR+PR)为52.6%,肿瘤控制率(CR+PR+SD)为86.8%.常见不良反应主要表现为骨髓抑制、胃肠道反应和手足综合征等,均可耐受,无治疗相关死亡患者.结论 多西他赛联合卡培他滨治疗晚期乳腺癌近期能取得较好的疗效,且毒副反应可以耐受,可以作为晚期乳腺癌的有效解救治疗方案.

  20. The effect of Gemcitabine combined Capecitabine regimens for anthracycline- and taxane- refractory metastatic breast cancer%吉西他滨联合卡培他滨治疗蒽环类和紫杉类耐药的转移性乳腺癌

    Institute of Scientific and Technical Information of China (English)

    王峥; 康华峰; 王西京; 董济民

    2011-01-01

    目的:观察吉西他滨( Gemcitabine) 联合卡培他滨(Capecitabine) 治疗蒽环类和紫杉类药物耐药的转移性乳腺癌患者的近期疗效和不良反应.方法:40例患者采用吉西他滨联合卡培他滨方案化疗:吉西他滨 1000mg/m2静脉滴注,第1 、8天;卡培他滨1000mg/m2口服,每日两次,第1-14天;21天为1周期.每2周期评价疗效,每周期进行毒性和安全性评估.结果:40例患者共接受156周期化疗,中位化疗周期4个(2-6个周期),总有效率(overall remission rate,RR)为35.00%(14/40),其中临床完全缓解率(clinical complete remission,cCR)为7.50% (3/40),部分缓解率(partial remission,PR)为 27.50% (11/40),稳定率(stable disease,SD)为 30.00% (12/40),进展率(progressive disease,PD)为 35.00%(14/40).结论:吉西他滨联合卡培他滨是治疗蒽环类和紫杉类药物耐药的转移性乳腺癌的有效方案,其血液学和非血液学毒性耐受性良好.%Objective:To evaluate the clinical effect and toxicity of Gemcitabine combined with Capecitabine regimens for anthracycline - and taxane - refractory metastatic breast cancer. Methods: All 40 patients with anthracycline - and taxane - refractory metastatic breast cancer were treated with regimen: Gemcitabine was given at a dose of 1000mg/m2 on day1 and day 8, Capecitabine was given at a dose of 1000mg/m2 , twice daily, on day 1 - 14,21 days was one cycle. Response rate was evaluated every two cycles and toxicity was evaluated every cycle. Results: All 40 patients received 156 cycles, overall remission rate ( RR ) was 35.00% ( 14/40 ), clinical complete remission rate ( cCR ) was 7.50% ( 3/40 ),partial remission rate ( PR ) was 27.50% ( 11/40 ), stable disease rate ( SD ) was 30.00% ( 12/40 ), progressive disease rate ( PD ) was 35.00% ( 14/40 ). Conclusion: Combination of Gemcitabine with Capecitabine regimen is an effective method to treat anthracycline - and taxane - refractory metastatic breast cancer with tolerable

  1. Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

    Institute of Scientific and Technical Information of China (English)

    Li Fan; Wen-Chao Liu; Yan-Jun Zhang; Jun Ren; Bo-Rong Pan; Du-Hu Liu; Yan Chen; Zhao-Cai Yu

    2005-01-01

    AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS: A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda (X group)or CF/5-FU (control group). Oral Xeloda 1 000 mg/m2was administered twice daily from d 1 to 14 in X group,while CF 200 mg/m2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups:cisplatin 60-80 mg/m2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m2 intravenously for 2 h on d 1. All the drugs were recycled every 21 d,with at least two cycles. Pyridoxine 50 mg was given t.i.d.orally for prophylaxis of the hand-foot syndrome (HFS).Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS: Hundred and fourteen cases (87.0%) finished more than two chemotherapy cycles. The overall response rate of them was 52.5% (X group) and 42.4% (control group) respectively. Tumor progression time (TTP) was 7.35 mo vs5.95 mo, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xeloda-related adverse events were myelosuppression,gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was $9 137.35(X group) and $8 961.72 (control group), or US $1 100.89in X group and $1 079.73 in control group. To add 1% to the response rate costs $ 161.44 vs $210

  2. 改良Hyper-CVAD/MA 方案治疗25例淋巴系统恶性肿瘤的临床分析%Clinical Analysis of 25 Patients with Lymphoid Malignancies Treated with Modified Hyper-Fractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Alternated with High-Dose Methotrexate and Cytarabine

    Institute of Scientific and Technical Information of China (English)

    刘蒙; 杨明珍; 夏瑞祥; 曾庆曙; 夏海龙; 王永庆

    2012-01-01

    目的:评价改良Hyper-CVAD/MA方案治疗国内成人急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤(NHL)的疗效及安全性.方法:对2006年5月至2011年6月接受改良Hyper-CVAD/MA方案治疗的17例成人ALL和8例NHL共25例的疗效和不良反应进行回顾性分析.结果:25例共完成40个周期A方案与29个周期B方案化疗,1年总体生存(OS)为(61.3±10.2)%.17例ALL 1年OS为(62.6±12.2)%.接受2~4个周期该方案化疗的患者与仅接受1个周期该方案化疗的患者相比,中位OS时间延长(P=0.046).8例NHL 1年OS为(60.0±18.2)%.接受4~7个周期该方案化疗的患者与接受2个周期该方案化疗的患者相比,中位OS时间延长(P=0.021).主要不良反应是骨髓抑制及感染,不良反应可控制,B方案的延长并未减低不良反应.结论:改良Hyper-CVAD/MA方案用于淋巴系统恶性肿瘤的治疗,疗效满意,治疗相关不良反应可控制,值得推广.%Objective: To evaluate the safety and therapeutic efficacy of a new treatment method for adult acute lymphoblastic leukemia ( ALL ) and non-Hodgkin's lymphoma ( NHL ) patients in China. The treatment was a modified regimen of hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone ( hyper-CVAD ) alternated with high-dose methotrexate and cytarabi-ne ( MA ). Methods: A retrospective analysis was done for 17 ALL and 8 NHL patients treated with the modified hyper-CVAD/MA regimen in the First Affiliated Hospital of Anhui Medical University between May 2006 to June 2011. The relevant safety and efficacy of the treatment regimen were evaluated. Results: All 25 patients underwent 40 cycles of the hyper-CVAD regimen and 29 cycles of the MA regimen. The one-year overall survival ( OS ) rate of the patients reached 61.3% ± 10.2% after the treatments. The one-year OS rate of the 17 adult ALL patients was 62.6% ± 12.2%. Compared with the patients who only received one cycle of the hyper-CVAD/MA regimen, those who

  3. 夫精宫腔内人工授精周期数与妊娠率的相关性分析%Correlation analysis on the pregnancy outcome and cycles of intrauterine insemination with husband sperm.

    Institute of Scientific and Technical Information of China (English)

    秘祖霞; 徐雯; 卢伟英; 张毅; 黄炜

    2012-01-01

    Objective To explore the correlation between the cycles of in trauterine insemination (IUI) with husband sperm and the pregnancy outcome. Methods A total of 2 196 IUI cycles were analyzed retrospectively. The relationship between the number of cycles of IUI and pregnancy rate was analyzed. Results 1 625 infertile couples were treated with 2 196 cycles of IUI. 329 cases were found with pregnancy. The pregnancy rate (PR) was 15% per cy-cle and 20.2% per couple. The clinical PR for the first, second, third and fourth cycle were 15.2%, 14.9%, 12.9% and 0.0%, respectively, with no statistically significant differences (P>0.05). The cycle PR for the one cycle, two cycle, three cycle, four cycle were 19.7%, 10.1%, 8.9%, 6.3%, respectively, with statistically significant difference between the one, two, three cycle. The cumulative pregnancy rates for the four groups were 19.7%, 20.2%, 26.7%, 25%, respec-tively, with no statistically significant differences (P>0.05). Conclusion Adding IUI cycles properly could increase the clinical pregnancy rate.%目的 分析夫精宫腔内人工授精(IUI)治疗周期数与临床结局的相互关系.方法 回顾性分析2196个IUI周期的病例资料,比较治疗周期次数与临床妊娠率的关系.结果 1 625例患者行2 196个IUI周期,有329例获临床妊娠,周期妊娠率为15%,夫妇累积妊娠率为20.2%.第1、第2、第3、第4周期组的临床妊娠率分别为15.2%、14.9%、12.9%、0.0%,各组间比较差异无统计学意义(P>0.05);1、2、3、4个周期组的周期临床妊娠率分别为19.7%、10.1%、8.9%、6.3%,累积妊娠率分别为19.7%、20.2%、26.7%、25.0%.两两比较分析显示1个周期组与2个周期组及3个周期组的周期临床妊娠率差异均有统计学意义(P<0.01),但其他组间比较差异无统计学意义(P>0.05);各组间累积妊娠率比较差异无统计学意义(P>0.05).结论 IUI治疗中适当增加助孕周期数可以增加累积临床妊娠率.

  4. A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

    International Nuclear Information System (INIS)

    The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip® Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available

  5. Imputing amino acid polymorphisms in human leukocyte antigens.

    Directory of Open Access Journals (Sweden)

    Xiaoming Jia

    Full Text Available DNA sequence variation within human leukocyte antigen (HLA genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals. We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918 with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.

  6. Systematising EAP Materials Development: Design, Evaluation and Revision in a Thai Undergraduate Reading Course

    OpenAIRE

    Sudajit-apa, Melada

    2008-01-01

    Materials design and evaluation have been regarded as inseparable processes for a systematic approach to materials development. But much less attention has been paid to the role and process of revision. This study reports a two-cycle approach to reading materials development for Thai undergraduate students: a first cycle of needs analysis, initial design, implementation and evaluation; and a second cycle of revision, implementation and re-evaluation. The two cycles involved bot...

  7. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth and invasion

    OpenAIRE

    Li, Yirong; Wang, Longgui; Zhang, Miao; Melamed, Jonathan; Liu, Xiaomei; Reiter, Robert; Wei, Jianjun; Peng, Yi; Zou, Xuanyi; Pellicer, Angel; Garabedian, Michael J.; Ferrari, Anna; Lee, Peng

    2009-01-01

    A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LE...

  8. Gene expression data (CEL files) - Open TG-GATEs | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available [ Credits ] BLAST Search Image Search Home About Archive Update History Contact us Open TG-GATEs Gene expres...sion data (CEL files) Data detail Data name Gene expression data (CEL files) Descri...Tab Separated Value (TSV) format is included. CEL is one of the file formats that expresses gene expression ...data (raw data) generated from Affymetrix GeneChip®. Data file File name: Gene expression data from rat samp...ze: 12.0GB total File name: Gene expression data from human samples File URL: ftp://ftp.biosciencedbc.jp/arc

  9. Development of a high density 600K SNP genotyping array for chicken

    OpenAIRE

    Kranis, Andreas; Gheyas, Almas A; Boschiero, Clarissa; Turner, Frances; Yu, Le; Smith, Sarah; Talbot, Richard; Pirani, Ali; Brew, Fiona; Kaiser, Pete; Hocking, Paul M.; Fife, Mark; Salmon, Nigel; Fulton, Janet; Strom, Tim M

    2013-01-01

    BACKGROUND: High density (HD) SNP genotyping arrays are an important tool for genetic analyses of animals and plants. Although the chicken is one of the most important farm animals, no HD array is yet available for high resolution genetic analysis of this species. RESULTS: We report here the development of a 600 K Affymetrix(R) Axiom(R) HD genotyping array designed using SNPs segregating in a wide variety of chicken populations. In order to generate a large catalogue of segregating SNPs, we r...

  10. Identification of a Novel, Recurrent HEY1-NCOA2 Fusion in Mesenchymal Chondrosarcoma based on a Genome-wide Screen of Exon-level Expression Data

    OpenAIRE

    Wang, Lu; Motoi, Toru; Khanin, Raya; Olshen, Adam,; Mertens, Fredrik; Bridge, Julia; Dal Cin, Paola; Antonescu, Cristina; Singer, Sam; Hameed, Meera; Bovee, Judith; Hogendoorn, Pancras C W; Socci, Nicholas; Ladanyi, Marc

    2011-01-01

    Cancer gene fusions that encode a chimeric protein are often characterized by an intragenic discontinuity in the RNA expression levels of the exons that are 5′ or 3′ to the fusion point in one or both of the fusion partners due to differences in the levels of activation of their respective promoters. Based on this, we developed an unbiased, genome-wide bioinformatic screen for gene fusions using Affymetrix Exon array expression data. Using a training set of 46 samples with different known gen...

  11. Whole-Genome Expression Analysis of Human Mesenchymal Stromal Cells Exposed to Ultrasmooth Tantalum vs. Titanium Oxide Surfaces

    DEFF Research Database (Denmark)

    Stiehler, C.; Bunger, C.; Overall, R. W.;

    2013-01-01

    Durable osseointegration of metallic bone implants requires that progenitor cells attach, proliferate and differentiate on the implant surface. Previously, we demonstrated superior biocompatibility of human mesenchymal stromal cells (MSCs) cultivated on ultrasmooth tantalum (Ta) as compared to...... MSCs cultivated on plain sputter-coated surfaces of Ta or Ti for 1, 2, 4, and 8 days were hybridized to n = 16 U133 Plus 2.0 arrays (Affymetrix(A (R))). Functional annotation, cluster and pathway analyses were performed. The vast majority of genes were differentially regulated after 4 days of...

  12. Jetset: selecting the optimal microarray probe set to represent a gene

    DEFF Research Database (Denmark)

    Li, Qiyuan; Birkbak, Nicolai Juul; Gyorffy, Balazs;

    2011-01-01

    Background: Interpretation of gene expression microarrays requires a mapping from probe set to gene. On many Affymetrix gene expression microarrays, a given gene may be detected by multiple probe sets, which may deliver inconsistent or even contradictory measurements. Therefore, obtaining an unam...... that were nominally detected by multiple probe sets, and we found that the probe set chosen by our method showed stronger concordance. Conclusions: This method provides a simple, unambiguous mapping to allow assessment of the expression levels of specific genes of interest....

  13. Genome-wide Gene Expression Analysis of Mucosal Colonic Biopsies and Isolated Colonocytes Suggests a Continuous Inflammatory State in the Lamina Propria of Patients with Quiescent Ulcerative Colitis

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Hansen, Morten; Olsen, Jørgen; Nielsen, Ole Haagen; Bjerrum, J.T.; Hansen, M.; Olsen, J.; Nielsen, O.H.

    2010-01-01

    syndrome (controls, n = 10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure......Background: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated...

  14. A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

    OpenAIRE

    Kreger Bernard E; Finger Daniel; Rosenberg Carol L; Murabito Joanne M; Levy Daniel; Splansky Greta; Antman Karen; Hwang Shih-Jen

    2007-01-01

    Abstract Background Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. Methods We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits – prostate cancer and breast cancer – in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multi...

  15. Genome-wide expression profiling during protection from colitis by regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna Ny; Olsen, Jørgen; Gad, Monika;

    2008-01-01

    Chip Mouse Genome 430 2.0 Array), which enabled an analysis of a complete set of RNA transcript levels in each sample. Array results were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Data were analyzed using combined projections to latent structures and functional...... pathways of importance for immune regulation in protected mice we studied the genome-wide expression profile in the inflamed rectum of SCID mice with CD4(+) T cell transfer colitis and in the uninflamed rectum of mice protected from colitis by Treg cells. We used DNA microarray technology (Affymetrix Gene...

  16. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne B; Dyrskjøt, Lars; von der Maase, Hans;

    2007-01-01

    and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry in...... strong independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...

  17. LD bin list (Phase III) - D-HaploDB | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available e greedy method of tagzilla (which is a rapid method of bin selection based on the principle of ldSELECT (Carso...es (Chr1 - Chr22, ChrX) Position Start Start position of LD bin (nucleotide position in each chromosome, according... to NCBI Build 36) Position End End position of LD bin (nucleotide position in each chromosome, according...togodb.biosciencedbc.jp/togodb/view/dhaplo_d3_ld_bin_list#en Data acquisition method Affymetrix SNP 6.0 Data analysis method Com...mon SNPs (MAF > 5%) were selected, and LDs (r 2 values) between every SNP pairs within

  18. Reproducibility of oligonucleotide microarray transcriptome analyses - An interlaboratory comparison using chemostat cultures of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Piper, M.D.W.; Daran-Lapujade, P.; Bro, Christoffer;

    2002-01-01

    -microarray analysis in functional genomics and metabolic engineering, we designed a set of experiments to specifically address this issue. Saccharomyces cerevisiae CEN.PK113-7D was grown under defined,conditions in, glucose-limited chemostats, followed by transcriptome analysis with Affymetrix Gene-Chip arrays. In...... each of the laboratories, three independent replicate cultures were grown aerobically as well as anaerobically. Although variations introduced by in vitro handling steps were small and unbiased, greater variation from replicate cultures underscored that, to obtain reliable information, experimental...

  19. Development and preliminary evaluation of a 90 K Axiom® SNP array for the allo-octoploid cultivated strawberry Fragaria × ananassa

    OpenAIRE

    Bassil, Nahla V.; Davis, Thomas M; Zhang, Hailong; Ficklin, Stephen; Mittmann, Mike; Webster, Teresa; Mahoney, Lise L.; Wood, David; Alperin, Elisabeth S; Umesh R Rosyara; Koehorst-vanc Putten, Herma; Monfort, Amparo; Sargent, Daniel J.; Amaya, Iraida; Denoyes, Beatrice

    2015-01-01

    Background A high-throughput genotyping platform is needed to enable marker-assisted breeding in the allo-octoploid cultivated strawberry Fragaria × ananassa. Short-read sequences from one diploid and 19 octoploid accessions were aligned to the diploid Fragaria vesca ‘Hawaii 4’ reference genome to identify single nucleotide polymorphisms (SNPs) and indels for incorporation into a 90 K Affymetrix® Axiom® array. We report the development and preliminary evaluation of this array. Results About 3...

  20. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    OpenAIRE

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gaël; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze. By using Affymetrix GeneChip microarrays, we found a distinc...

  1. Anti-Iipase and antioxidant properties of 30 medicinal plants used in Oaxaca, México

    OpenAIRE

    Nemesio Villa-Ruano; Guilibaldo G Zurita-Vásquez; Yesenia Pacheco-Hernández; Martha G Betancourt-Jiménez; Ramiro Cruz-Durán; Horacio Duque-Bautista

    2013-01-01

    We report the results of in vitro anti-lipase and antioxidant assays using crude ethanolic extracts from 30 plants grown in Oaxaca, México. Anti-lipase tests were performed by using porcine pancreatic lipase (PPL) [EC 3.1.1.3] from Affymetrix/USB. The extracts of Solanum erianthum, Salvia microphylla, Brungmansia suaveolens and Cuphea aequipetala showed up to 60% PPL inhibition. The effect of these extracts on the kinetic parameters of PPL (Km= 0.36 mM, and Vmax=0.085 mM min -1) revealed that...

  2. Comparative analysis of root transcriptomes from two contrasting drought-responsive Williams 82 and DT2008 soybean cultivars under normal and dehydration conditions

    OpenAIRE

    Ha, Chien Van; Watanabe, Yasuko; Tran, Uyen Thi; Le, Dung Tien; Tanaka, Maho; Nguyen, Kien Huu; Seki, Motoaki; Nguyen, Dong Van; Tran, Lam-Son Phan

    2015-01-01

    The economically important DT2008 and the model Williams 82 (W82) soybean cultivars were reported to have differential drought-tolerant degree to dehydration and drought, which was associated with root trait. Here, we used 66K Affymetrix Soybean Array GeneChip to compare the root transcriptomes of DT2008 and W82 seedlings under normal, as well as mild (2 h treatment) and severe (10 h treatment) dehydration conditions. Out of the 38172 soybean genes annotated with high confidence, 822 (2.15%) ...

  3. Comparative analysis of temporal gene expression patterns in the developing ovary of the embryonic chicken

    OpenAIRE

    YU, Minli; Xu,Yali; YU, Defu; YU, Debing; DU, Wenxing

    2015-01-01

    Many genes participate in the process of ovarian germ cell development, while the combined action mechanisms of these molecular regulators still need clarification. The present study was focused on determination of differentially expressed genes and gene functions at four critical time points in chicken ovarian development. Comparative transcriptional profiling of ovaries from embryonic day 5.5 (E5.5), E12.5, E15.5 and E18.5 was performed using an Affymetrix GeneChip chicken genome microarray...

  4. Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China

    OpenAIRE

    Hu, Nan; Wang, Chaoyu; Ng, David; Clifford, Robert; Yang, Howard H.; Tang, Ze-Zhong; Wang, Quan-Hong; Han, Xiao-You; Giffen, Carol; Goldstein, Alisa M; Taylor, Philip R.; Lee, Maxwell P.

    2009-01-01

    Genomic instability plays an important role in most human cancers. To characterize genomic instability in esophageal squamous cell carcinoma (ESCC), we examined loss of heterozygosity (LOH), copy number (CN) loss, CN gain, and gene expression using the Affymetrix GeneChip Human Mapping 500K (n=30 cases) and Human U133A (n=17 cases) arrays in ESCC cases from a high-risk region of China. We found that genomic instability measures varied widely among cases and separated them into two groups: a h...

  5. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;

    2006-01-01

    gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  6. Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains

    OpenAIRE

    Malki, Karim; Mineur, Yann S.; Tosto, Maria Grazia; Campbell, James; Karia, Priya; Jumabhoy, Irfan; Sluyter, Frans; Crusio, Wim E.; Schalkwyk, Leonard C

    2015-01-01

    Background BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and...

  7. Mapping transcriptome profiles of in vitro iPSC-derived cardiac differentiation to in utero heart development

    OpenAIRE

    Xing Li; Campbell, Katherine A; Biendarra, Sherri M.; Andre Terzic; Nelson, Timothy J

    2015-01-01

    The dataset includes microarray data (Affymetrix Mouse Genome 430 2.0 Array) from WT and Nos3−/− mouse embryonic heart ventricular tissues at 14.5 days post coitum (E14.5), induced pluripotent stem cells (iPSCs) derived from WT and Nos3−/− mouse tail tip fibroblasts, iPSC-differentiated cardiomyocytes at Day 11, and mouse embryonic stem cells (mESCs) and differentiated cardiomyocytes as positive controls for mouse iPSC differentiation. Both in utero (using embryonic heart tissues) and in vitr...

  8. Loss of heterozygosity analyzed by single nucleotide polymorphisrn array in cancer

    Institute of Scientific and Technical Information of China (English)

    HaiTao Zheng; ZhiHai Peng; Sheng Li; Lin He

    2005-01-01

    Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function.Loss of heterozygosity (LOH) has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. LOH pattern has been detected by allelotyping using restriction fragment length polymorphism, and later by simple sequence length polymorphisms (SSLPs or microsatellite) for 10 years.This paper reviews the detection of LOH by recently developed single nucleotide polymorphism (SNP) arrays (all analyzed by Affymetrix array); furthermore, its advantage and disadvantage were analyzed in several kinds of cancer.

  9. Molecular characterization of the submergence response of Arabidopsis thaliana ecotype Columbia

    DEFF Research Database (Denmark)

    Lee, S.C.; Mustroph, A.; Sasidaharan, R.;

    2011-01-01

    A detailed description of the molecular response of Arabidopsis thaliana to submergence can aid the identification of genes that are critical to flooding survival. • Rosette-stage plants were fully submerged in complete darkness and shoot and root tissue was harvested separately after the O2...... partial pressure of the petiole and root had stabilized at c. 6 and 0.1 kPa, respectively. As controls, plants were untreated or exposed to darkness. Following quantitative profiling of cellular mRNAs with the Affymetrix ATH1 platform, changes in the transcriptome in response to submergence, early...

  10. Peripheral Blood Based Discrimination of Ulcerative Colitis and Crohn’s Disease from Non-IBD Colitis by Genome-Wide Gene Expression Profiling

    OpenAIRE

    Ferenc Sipos; Orsolya Galamb; Barnabás Wichmann; Tibor Krenács; Kinga Tóth; Katalin Leiszter; Györgyi Műzes; Tamás Zágoni; Zsolt Tulassay; Béla Molnár

    2011-01-01

    A molecular diagnostic assay using easily accessible peripheral blood would greatly assist in the screening and diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). Transcriptional profiles in blood/biopsy samples from 12 UC (6/12), 9 CD (5/9), 6 non-inflammatory bowel disease (non-IBD) colitis (6/0), and 11 healthy (11/11) patients were assessed by Affymetrix HGU133Plus2.0 microarrays. Prediction analysis of microarrays, discriminant and ROC analyses were performed, the results wer...

  11. MicroRNA profiling in human neutrophils during bone marrow granulopoiesis and in vivo exudation

    DEFF Research Database (Denmark)

    Larsen, Maria T; Hother, Christoffer; Häger, Mattias;

    2013-01-01

    The purpose of this study was to describe the microRNA (miRNA) expression profiles of neutrophils and their precursors from the initiation of granulopoiesis in the bone marrow to extravasation and accumulation in skin windows. We analyzed three different cell populations from human bone marrow......, polymorphonuclear neutrophil (PMNs) from peripheral blood, and extravasated PMNs from skin windows using the Affymetrix 2.0 platform. Our data reveal 135 miRNAs differentially regulated during bone marrow granulopoiesis. The majority is differentially regulated between the myeloblast/promyelocyte (MB/PM) and...

  12. Array2BIO: from microarray expression data to functional annotation of co-regulated genes

    Directory of Open Access Journals (Sweden)

    Rasley Amy

    2006-06-01

    Full Text Available Abstract Background There are several isolated tools for partial analysis of microarray expression data. To provide an integrative, easy-to-use and automated toolkit for the analysis of Affymetrix microarray expression data we have developed Array2BIO, an application that couples several analytical methods into a single web based utility. Results Array2BIO converts raw intensities into probe expression values, automatically maps those to genes, and subsequently identifies groups of co-expressed genes using two complementary approaches: (1 comparative analysis of signal versus control and (2 clustering analysis of gene expression across different conditions. The identified genes are assigned to functional categories based on Gene Ontology classification and KEGG protein interaction pathways. Array2BIO reliably handles low-expressor genes and provides a set of statistical methods for quantifying expression levels, including Benjamini-Hochberg and Bonferroni multiple testing corrections. An automated interface with the ECR Browser provides evolutionary conservation analysis for the identified gene loci while the interconnection with Crème allows prediction of gene regulatory elements that underlie observed expression patterns. Conclusion We have developed Array2BIO – a web based tool for rapid comprehensive analysis of Affymetrix microarray expression data, which also allows users to link expression data to Dcode.org comparative genomics tools and integrates a system for translating co-expression data into mechanisms of gene co-regulation. Array2BIO is publicly available at http://array2bio.dcode.org.

  13. Sequence-matched probes produce increased cross-platform consistency and more reproducible biological results in microarray-based gene expression measurements.

    Science.gov (United States)

    Mecham, Brigham H; Klus, Gregory T; Strovel, Jeffrey; Augustus, Meena; Byrne, David; Bozso, Peter; Wetmore, Daniel Z; Mariani, Thomas J; Kohane, Isaac S; Szallasi, Zoltan

    2004-01-01

    Cancer derived microarray data sets are routinely produced by various platforms that are either commercially available or manufactured by academic groups. The fundamental difference in their probe selection strategies holds the promise that identical observations produced by more than one platform prove to be more robust when validated by biology. However, cross-platform comparison requires matching corresponding probe sets. We are introducing here sequence-based matching of probes instead of gene identifier-based matching. We analyzed breast cancer cell line derived RNA aliquots using Agilent cDNA and Affymetrix oligonucleotide microarray platforms to assess the advantage of this method. We show, that at different levels of the analysis, including gene expression ratios and difference calls, cross-platform consistency is significantly improved by sequence- based matching. We also present evidence that sequence-based probe matching produces more consistent results when comparing similar biological data sets obtained by different microarray platforms. This strategy allowed a more efficient transfer of classification of breast cancer samples between data sets produced by cDNA microarray and Affymetrix gene-chip platforms. PMID:15161944

  14. Identification of Potential Anticancer Activities of Novel Ganoderma lucidum Extracts Using Gene Expression and Pathway Network Analysis.

    Science.gov (United States)

    Kao, Chi H J; Bishop, Karen S; Xu, Yuanye; Han, Dug Yeo; Murray, Pamela M; Marlow, Gareth J; Ferguson, Lynnette R

    2016-01-01

    Ganoderma lucidum (lingzhi) has been used for the general promotion of health in Asia for many centuries. The common method of consumption is to boil lingzhi in water and then drink the liquid. In this study, we examined the potential anticancer activities of G. lucidum submerged in two commonly consumed forms of alcohol in East Asia: malt whiskey and rice wine. The anticancer effect of G. lucidum, using whiskey and rice wine-based extraction methods, has not been previously reported. The growth inhibition of G. lucidum whiskey and rice wine extracts on the prostate cancer cell lines, PC3 and DU145, was determined. Using Affymetrix gene expression assays, several biologically active pathways associated with the anticancer activities of G. lucidum extracts were identified. Using gene expression analysis (real-time polymerase chain reaction [RT-PCR]) and protein analysis (Western blotting), we confirmed the expression of key genes and their associated proteins that were initially identified with Affymetrix gene expression analysis. PMID:27006591

  15. Genome-wide transcriptional analysis of super-embryogenic Medicago truncatula explant cultures

    Directory of Open Access Journals (Sweden)

    Rolfe Barry G

    2008-10-01

    Full Text Available Abstract Background The Medicago truncatula (M. truncatula line 2HA has a 500-fold greater capacity to regenerate plants in culture by somatic embryogenesis than its wild type progenitor Jemalong. To understand the molecular basis for the regeneration capacity of this super-embryogenic line 2HA, using Affymetrix GeneChip®, we have compared transcriptomes of explant leaf cultures of these two lines that were grown on media containing the auxin NAA (1-naphthaleneacetic acid and the cytokinin BAP (6-benzylaminopurine for two weeks, an early time point for tissue culture proliferation. Results Using Affymetrix GeneChip®, GCRMA normalisation and statistical analysis, we have shown that more than 196 and 49 probe sets were significantly (p RESPONSE REGULATOR 10, AGAMOUS-LIKE 20, flower promoting factor 1, nodulin 3, fasciclin and lipoxygenase, and a down-regulated gene ETHYLENE INSENSITIVE 3, all of which positively correlated with the microarray data. Conclusion We have described the differences in transcriptomes between the M. truncatula super-embryogenic line 2HA and its non-embryogenic progenitor Jemalong at an early time point. This data will facilitate the mapping of regulatory and metabolic networks involved in the gaining totipotency and regeneration capacity in M. truncatula and provides candidate genes for functional analysis.

  16. Characterization of adjacent breast tumors using oligonucleotide microarrays

    International Nuclear Information System (INIS)

    Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles. Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip® (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite® 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN® 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics. The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710. Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making

  17. High-Sensitivity Transcriptome Data Structure and Implications for Analysis and Biologic Interpretation

    Institute of Scientific and Technical Information of China (English)

    Sebastian Noth; Guillaume Brysbaert; Fran(c)ois-Xavier Pellay; Arndt Benecke

    2006-01-01

    Novel microarray technologies such as the AB1700 platform from Applied Biosystems promise significant increases in the signal dynamic range and a higher sensitivity for weakly expressed transcripts. We have compared a representative set of AB1700 data with a similarly representative Affymetrix HG-U133A dataset. The AB1700 design extends the signal dynamic detection range at the lower bound by one order of magnitude. The lognormal signal distribution profiles of these highsensitivity data need to be represented by two independent distributions. The additional second distribution covers those transcripts that would have gone undetected using the Affymetrix technology. The signal-dependent variance distribution in the AB1700 data is a non-trivial function of signal intensity, describable using a composite function. The drastically different structure of these highsensitivity transcriptome profiles requires adaptation or even redevelopment of the standard microarray analysis methods. Based on the statistical properties, we have derived a signal variance distribution model for AB1700 data that is necessary for such development. Interestingly, the dual lognormal distribution observed in the AB1700 data reflects two fundamentally different biologic mechanisms of transcription initiation.

  18. Integrated Genomic Analysis of Sézary Syndrome

    Directory of Open Access Journals (Sweden)

    Xin Mao

    2011-01-01

    Full Text Available Sézary syndrome (SS is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1 frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2 reduced SNP copy number at FAT gene (4q35 in 75% of SS cases, and (3 the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.

  19. Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes

    Directory of Open Access Journals (Sweden)

    Lang Thierry

    2009-03-01

    Full Text Available Abstract Background Mammal macrophages (MΦ display a wide range of functions which contribute to surveying and maintaining tissue integrity. One such function is phagocytosis, a process known to be subverted by parasites like Leishmania (L. Indeed, the intracellular development of L. amazonensis amastigote relies on the biogenesis and dynamic remodelling of a phagolysosome, termed the parasitophorous vacuole, primarily within dermal MΦ. Results Using BALB/c mouse bone marrow-derived MΦ loaded or not with amastigotes, we analyzed the transcriptional signatures of MΦ 24 h later, when the amastigote population was growing. Total RNA from MΦ cultures were processed and hybridized onto Affymetrix Mouse430_2 GeneChips®, and some transcripts were also analyzed by Real-Time quantitative PCR (RTQPCR. A total of 1,248 probe-sets showed significant differential expression. Comparable fold-change values were obtained between the Affymetrix technology and the RTQPCR method. Ingenuity Pathway Analysis software® pinpointed the up-regulation of the sterol biosynthesis pathway (p-value = 1.31e-02 involving several genes (1.95 to 4.30 fold change values, and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signalling. Conclusion Our findings suggest that the amastigote growth relies on early coordinated gene expression of the MΦ lipid and polyamine pathways. Moreover, these MΦ hosting multiplying L. amazonensis amastigotes display a transcriptional profile biased towards parasite-and host tissue-protective processes.

  20. The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.

    Science.gov (United States)

    Hu, Qinyong; Chu, Yuxin; Song, Qibin; Yao, Yi; Yang, Weihong; Huang, Shiang

    2016-08-01

    This study aims to investigate the prevalence and distribution of diverse chromosomal aberrations associated with myelodysplastic syndromes (MDS) in China. Bone marrow samples were collected from multiple cities in China. Metaphase cytogenetic (MC) analysis and fluorescence in situ hybridization (FISH) were initially used to test chromosomal lesions. Affymetrix CytoScan 750 K genechip platform performed a genome-wide detection of chromosomal aberrations. Chromosomal gain was identified in 76 patients; the most prevalent was trisomy 8(17.9 %). New chromosomal gain was detected on chromosome 9, 19p, and X. Chromosomal loss was detected in 101 patients. The most frequent was loss 5q (21.0 %). Some loss and gain were not identified by MC or FISH but identified by genechip. UPD was solely identified by genechip in 51 patients; the most prevalent were UPD 7q (4.94 %) and UPD 17p (4.32 %). Furthermore, complex chromosomal aberrations were detected in 56 patients. In conclusion, Affymetrix CytoScan 750 K genechip was more precise than MC and FISH in detection of cryptic chromosomal aberrations relevant to MDS. Analysis of the prevalence and distribution of diverse chromosomal aberrations in China may improve strategies for MDS diagnosis and therapies. PMID:27225263

  1. Case-Control Genome-Wide Association of Attention-Deficit / Hyperactivity Disorder

    Science.gov (United States)

    Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J.L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schäfer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Biederman, Joseph

    2010-01-01

    Objective Although twin and family studies have shown attention deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus, additional genomewide association studies (GWAS) are needed. Method We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. The data were analyzed using a generalized linear model. Results No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1 and HKDC1. Conclusions The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles. PMID:20732627

  2. Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis

    Directory of Open Access Journals (Sweden)

    Binder Jochen

    2009-04-01

    Full Text Available Abstract Background Interstitial cystitis (IC, a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Results Gene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix – GeneChip® Human Genome U133 Plus 2.0. More than 31,000 of > 54,000 tested probe sets were present (detection p-value Conclusion GeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC will further indicate whether the data presented here will be valuable for the diagnosis of IC.

  3. Bayesian Modeling of ChIP-chip Data Through a High-Order Ising Model

    KAUST Repository

    Mo, Qianxing

    2010-01-29

    ChIP-chip experiments are procedures that combine chromatin immunoprecipitation (ChIP) and DNA microarray (chip) technology to study a variety of biological problems, including protein-DNA interaction, histone modification, and DNA methylation. The most important feature of ChIP-chip data is that the intensity measurements of probes are spatially correlated because the DNA fragments are hybridized to neighboring probes in the experiments. We propose a simple, but powerful Bayesian hierarchical approach to ChIP-chip data through an Ising model with high-order interactions. The proposed method naturally takes into account the intrinsic spatial structure of the data and can be used to analyze data from multiple platforms with different genomic resolutions. The model parameters are estimated using the Gibbs sampler. The proposed method is illustrated using two publicly available data sets from Affymetrix and Agilent platforms, and compared with three alternative Bayesian methods, namely, Bayesian hierarchical model, hierarchical gamma mixture model, and Tilemap hidden Markov model. The numerical results indicate that the proposed method performs as well as the other three methods for the data from Affymetrix tiling arrays, but significantly outperforms the other three methods for the data from Agilent promoter arrays. In addition, we find that the proposed method has better operating characteristics in terms of sensitivities and false discovery rates under various scenarios. © 2010, The International Biometric Society.

  4. Identification of two genes potentially associated in iron-heme homeostasis in human carotid plaque using microarray analysis

    Indian Academy of Sciences (India)

    Hanène Ayari; Giampiero Bricca

    2013-06-01

    Classic characteristics are poor predictors of the risk of thromboembolism. Thus, better markers for the carotid atheroma plaque formation and symptom causing are needed. Our objective was to study by microarray analysis gene expression of genes involved in homeostasis of iron and heme in carotid atheroma plaque from the same patient. mRNA gene expression was measured by an Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 68 specimens of endarteriectomy from 34 patients. Two genes involved in iron-heme homeostasis, CD163 and heme oxygenase (HO-1), were analysed in 34 plaques. CD163 (2.18, =1.45E−08) and HO-1 (fold-change 2.67, =2.07E−09) mRNAs were induced. We suggest that atheroma plaques show a more pronounced induction of CD163 and HO-1. Although further evidence is needed, our results support previous data. To our knowledge, this is the first report comparing gene expression between intact arterial tissue and carotid plaque using microarray analysis.

  5. An overview of custom array sequencing.

    Science.gov (United States)

    Kothiyal, Prachi; Cox, Stephanie; Ebert, Jonathan; Aronow, Bruce J; Greinwald, John H; Rehm, Heidi L

    2009-04-01

    This unit provides an overview of oligo hybridization-based resequencing and a wide range of considerations for implementing the technology and analyzing the resulting data. The specific technology discussed is the Affymetrix GeneChip CustomSeq Resequencing Array platform. Concepts related to array design, experimental protocols, and base-calling using existing algorithms are presented. Details that should be evaluated during development of sequence tiling, target amplification, and PCR protocols are addressed. An overview of the Affymetrix GeneChip Sequence Analysis Software (GSEQ) is provided, along with factors that influence base-calling coverage and accuracy. Also outlined are performance measures that can be used to characterize base-calling with resequencing arrays, as well as factors known to affect their performance. Limitations associated with detection of insertions and deletions (indels) are discussed, with empirical data from our experiments used to outline possible approaches to indel detection. Critical topics in the design, implementation, and analysis of targeted sequencing arrays not previously discussed in detail are highlighted. PMID:19360699

  6. Expression profiling of human renal carcinomas with functional taxonomic analysis

    Directory of Open Access Journals (Sweden)

    Madore Steven J

    2002-09-01

    Full Text Available Abstract Background Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. Results We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p Conclusions Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.

  7. A Family with Mental Retardation, Epilepsy and Cerebellar Hypoplasia Showing Linkage to Chromosome 20p11.21-q11.23

    Directory of Open Access Journals (Sweden)

    Fatih Bayrakli

    2014-01-01

    Full Text Available Background: Cerebellar hypoplasia (CH is a rare malformation caused by various etiologies, usually manifesting clinically as nonprogressive cerebellar ataxia with or without mental retardation. The molecular pathogenesis of the autosomal recessive cerebellar ataxias has a wide range of mechanisms. Differential diagnosis and categorization of the recessive cerebellar ataxias, however, need more specific, biochemical and genetic investigation. Methods: This study applied whole-genome linkage analysis to study a family with nonprogressive cerebellar ataxia and additional mental retardation, epilepsy, and facial dysmorphic features. Genotyping and linkage analysis was done using the GeneChip Mapping 250K NspI Array (Affymetrix Inc., Santa Clara, Calif., USA for genome-wide linkage analysis of the genotyping data from the affected children and their parents. Results: Allegro software version 1.2 was used for multipoint linkage analysis. We assumed an autosomal recessive inheritance pattern and assigned a penetrance of 0.999. Single-nucleotide polymorphism allele frequencies were estimated from the Affymetrix data of the Caucasian family studied. Using these parameters, a theoretical maximum logarithm of the odds score of 2.69 was identified at chromosome 20p11.21-q11.23. Conclusions: This chromosomal locus is unprecedented in autosomal recessive and nonprogressive ataxia disorder. Further investigation might reveal a new causative gene generating the CH phenotype.

  8. Partitioning of copy-number genotypes in pedigrees

    Directory of Open Access Journals (Sweden)

    Andelfinger Gregor U

    2010-05-01

    Full Text Available Abstract Background Copy number variations (CNVs and polymorphisms (CNPs have only recently gained the genetic community's attention. Conservative estimates have shown that CNVs and CNPs might affect more than 10% of the genome and that they may be at least as important as single nucleotide polymorphisms in assessing human variability. Widely used tools for CNP analysis have been implemented in Birdsuite and PLINK for the purpose of conducting genetic association studies based on the unpartitioned total number of CNP copies provided by the intensities from Affymetrix's Genome-Wide Human SNP Array. Here, we are interested in partitioning copy number variations and polymorphisms in extended pedigrees for the purpose of linkage analysis on familial data. Results We have developed CNGen, a new software for the partitioning of copy number polymorphism using the integrated genotypes from Birdsuite with the Affymetrix platform. The algorithm applied to familial trios or extended pedigrees can produce partitioned copy number genotypes with distinct parental alleles. We have validated the algorithm using simulations on a complex pedigree structure using frequencies calculated from a real dataset of 300 genotyped samples from 42 pedigrees segregating a congenital heart defect phenotype. Conclusions CNGen is the first published software for the partitioning of copy number genotypes in pedigrees, making possible the use CNPs and CNVs for linkage analysis. It was implemented with the Python interpreter version 2.5.2. It was successfully tested on current Linux, Windows and Mac OS workstations.

  9. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

    Science.gov (United States)

    van Dam, Peter A.; van Dam, Pieter-Jan H. H.; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A. A.; van Laere, Steven

    2016-01-01

    An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

  10. Cross-platform expression profiling demonstrates that SV40 small tumor antigen activates Notch, Hedgehog, and Wnt signaling in human cells

    International Nuclear Information System (INIS)

    We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including several components of the Wnt, Notch, and Hedgehog signaling pathways, consistent with SV40 ST activation of these developmental pathways. While inhibitors of Notch activation had no effect on cell survival, cyclopamine had a potent killing effect on cells expressing SV40 ST. CONCLUSIONS: These data show that SV40 ST expression alters cell survival pathways to sensitize cells to the killing effect of Hedgehog pathway inhibitors

  11. Construction of a versatile SNP array for pyramiding useful genes of rice.

    Science.gov (United States)

    Kurokawa, Yusuke; Noda, Tomonori; Yamagata, Yoshiyuki; Angeles-Shim, Rosalyn; Sunohara, Hidehiko; Uehara, Kanako; Furuta, Tomoyuki; Nagai, Keisuke; Jena, Kshirod Kumar; Yasui, Hideshi; Yoshimura, Atsushi; Ashikari, Motoyuki; Doi, Kazuyuki

    2016-01-01

    DNA marker-assisted selection (MAS) has become an indispensable component of breeding. Single nucleotide polymorphisms (SNP) are the most frequent polymorphism in the rice genome. However, SNP markers are not readily employed in MAS because of limitations in genotyping platforms. Here the authors report a Golden Gate SNP array that targets specific genes controlling yield-related traits and biotic stress resistance in rice. As a first step, the SNP genotypes were surveyed in 31 parental varieties using the Affymetrix Rice 44K SNP microarray. The haplotype information for 16 target genes was then converted to the Golden Gate platform with 143-plex markers. Haplotypes for the 14 useful allele are unique and can discriminate among all other varieties. The genotyping consistency between the Affymetrix microarray and the Golden Gate array was 92.8%, and the accuracy of the Golden Gate array was confirmed in 3 F2 segregating populations. The concept of the haplotype-based selection by using the constructed SNP array was proofed. PMID:26566831

  12. An epidural neuroblastoma causing spinal cord compression in a 67-year-old woman

    Directory of Open Access Journals (Sweden)

    Ethan Taub

    2010-04-01

    Full Text Available We report a case of disseminated neuroblastoma (NB causing epidural spinal cord compression in a 67-year-old woman. Because NB is primarily a tumor of infancy and childhood, less is known about its clinical course and optimal treatment in adults. This patient was treated with a thoracic laminectomy and tumor resection; polychemotherapy with one cycle of vindesine, cisplatin, and etoposide; one cycle of vincristine, dacarbazine, ifosfamide, and doxorubicin; and radiotherapy to the spine. She remained able to walk but died 8.5 months later of diffuse systemic tumor progression.

  13. The Medicago truncatula gene expression atlas web server

    Directory of Open Access Journals (Sweden)

    Tang Yuhong

    2009-12-01

    Full Text Available Abstract Background Legumes (Leguminosae or Fabaceae play a major role in agriculture. Transcriptomics studies in the model legume species, Medicago truncatula, are instrumental in helping to formulate hypotheses about the role of legume genes. With the rapid growth of publically available Affymetrix GeneChip Medicago Genome Array GeneChip data from a great range of tissues, cell types, growth conditions, and stress treatments, the legume research community desires an effective bioinformatics system to aid efforts to interpret the Medicago genome through functional genomics. We developed the Medicago truncatula Gene Expression Atlas (MtGEA web server for this purpose. Description The Medicago truncatula Gene Expression Atlas (MtGEA web server is a centralized platform for analyzing the Medicago transcriptome. Currently, the web server hosts gene expression data from 156 Affymetrix GeneChip® Medicago genome arrays in 64 different experiments, covering a broad range of developmental and environmental conditions. The server enables flexible, multifaceted analyses of transcript data and provides a range of additional information about genes, including different types of annotation and links to the genome sequence, which help users formulate hypotheses about gene function. Transcript data can be accessed using Affymetrix probe identification number, DNA sequence, gene name, functional description in natural language, GO and KEGG annotation terms, and InterPro domain number. Transcripts can also be discovered through co-expression or differential expression analysis. Flexible tools to select a subset of experiments and to visualize and compare expression profiles of multiple genes have been implemented. Data can be downloaded, in part or full, in a tabular form compatible with common analytical and visualization software. The web server will be updated on a regular basis to incorporate new gene expression data and genome annotation, and is accessible

  14. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  15. Influence of Phosphate on the Growth and Nodulation Characteristics of Rhizobium trifolii†

    OpenAIRE

    Leung, Kamtin; Bottomley, Peter J.

    1987-01-01

    The growth and nodulating characteristics of Rhizobium trifolii 6 and 36 differed under different external phosphate conditions. Under growth conditions designed to deplete the internal phosphate content of the rhizobia, strain 6 maintained a generation time of 5 h during the exponential phase over two cycles of growth in phosphate-depleted medium. In contrast, the generation time of strain 36 was extended from 3.5 to 9.8 h over two cycles of phosphate-depleted growth, although the organism e...

  16. A conjugate direction method for approximating the analytic center of a polytope

    OpenAIRE

    Megiddo Nimrod; Mizuno Shinji; Kojima Masakazu

    1998-01-01

    The analytic center of an -dimensional polytope with a nonempty interior is defined as the unique minimizer of the logarithmic potential function over . It is shown that one cycle of a conjugate direction method, applied to the potential function at any such that , generates a point such that .

  17. Technické památky jako součást cestovního ruchu v oblasti Týna nad Vltavou

    OpenAIRE

    DOBEŠ, Jakub

    2012-01-01

    This thesis processes a database of technical monuments in the city of Týn nad Vltavou and its surroundings. There was made a survey and controlled interviews with local businessmen and on its basis two plans of tourist routes and one cycle route were created. These plans of technical monuments include also its financing and project of new bike rentals.

  18. HLW flowsheet material balance for DWPF rad operation with Tank 51 sludge and ITP Cycle 1 precipitate

    International Nuclear Information System (INIS)

    This document presents the details of the Savannah River Plant Flowsheet for the Rad Operation with Tank Sludge and ITP Cycle 1 Precipitate. Topics discussed include: material balance; radiolysis chemistry of tank precipitates; algorithm for ESP washing; chemistry of hydrogen and ammonia generation in CPC; batch sizes for processing feed; and total throughput of a streams during one cycle of operation

  19. Control of the beam-internal target interaction at the Nuclotron by means of light radiation

    International Nuclear Information System (INIS)

    The light radiation from various internal targets at the Nuclotron can be utilized for the operative control and time optimization of the interaction intensity of the beam. The examples presented in the paper illustrate the information about space characteristics of the circulating beam during one cycle of the accelerator run at the stages of injection, acceleration and during the physical experiments. (author)

  20. 16 CFR 1500.52 - Test methods for simulating use and abuse of toys and other articles intended for use by children...

    Science.gov (United States)

    2010-01-01

    ... additional 10 seconds. During the test the toy is to rest on a flat, hard surface in any convenient position. ... be dropped in random orientation. After each drop, the test sample shall be allowed to come to rest... repeated for 30 cycles at a rate of one cycle per two seconds with a 60-second rest period occurring...

  1. 16 CFR 1500.51 - Test methods for simulating use and abuse of toys and other articles intended for use by children...

    Science.gov (United States)

    2010-01-01

    ... toy is to rest on a flat, hard surface in any convenient position. EC03OC91.059 ... random orientation. After each drop, the test sample shall be allowed to come to rest and shall be... of one cycle per two seconds with a 60-second rest period occurring after each 10 cycles. Two...

  2. [Hypocomplementemic urticarial vasculitis syndrome. Successful therapy with intravenous immunoglobulins].

    Science.gov (United States)

    Staubach-Renz, P; von Stebut, E; Bräuninger, W; Maurer, M; Steinbrink, K

    2007-08-01

    Autoimmune diseases can initially present as chronic urticaria. We describe the course of a patient with hypocomplementemic urticarial vasculitis syndrome (HUVS) as well as his successful treatment with high-dose intravenous immunoglobulins (IVIG). HUVS was diagnosed clinically and confirmed by histology and laboratory studies. After only one cycle with IVIG (2 g/kg) all HUVS symptoms were significantly decreased. PMID:17453168

  3. Fluctuation Relation for Heat Engines

    OpenAIRE

    Sinitsyn, N. A.

    2011-01-01

    We derive the exact equality, referred to as the fluctuation relation for heat engines (FRHE), that relates statistics of heat extracted from one of the two heat baths and the work per one cycle of a heat engine operation. Carnot's inequality of classical thermodynamics follows as a direct consequence of the FRHE.

  4. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N; De Wit, R; De Santis, M; Dumez, H; Marreaud, S; Collette, L; Lluch, J R G; Bokemeyer, C; Schmoll, H J

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-progno...

  5. The number of independent sets in unicyclic graphs

    DEFF Research Database (Denmark)

    Pedersen, Anders Sune; Vestergaard, Preben Dahl

      In this paper, we determine upper and lower bounds for the number of independent sets in a unicyclic graph in terms of its order. This gives an upper bound for the number of independent sets in a connected graph which contains at least one cycle. We also determine the upper bound for the number...

  6. 40 CFR 60.1750 - What is the minimum amount of monitoring data I must collect with my continuous emission...

    Science.gov (United States)

    2010-07-01

    ... and Compliance Times for Small Municipal Waste Combustion Units Constructed on or Before August 30.... Make sure the averages for sulfur dioxide, nitrogen oxides (Class I municipal waste combustion units...) requires your continuous emission monitoring systems to complete at least one cycle of operation...

  7. 40 CFR 63.7947 - What are my monitoring alternatives?

    Science.gov (United States)

    2010-07-01

    ... emissions CEMS) and Performance Specification 3 (for an O2 or CO2 CEMS) of 40 CFR part 60, appendix B. The... concentration. (1) The CEMS used on combustion control devices must include a diluent gas monitoring system (for... excess air). (2) Each CEMS must complete a minimum of one cycle of operation (sampling, analyzing,...

  8. 40 CFR 63.864 - Monitoring requirements.

    Science.gov (United States)

    2010-07-01

    ...) National Emission Standards for Hazardous Air Pollutants for Chemical Recovery Combustion Sources at Kraft...) (3) As specified in § 63.8(c)(4)(i), each COMS must complete a minimum of one cycle of sampling and... kiln, sulfite combustion unit, or kraft or soda smelt dissolving tank equipped with a wet scrubber...

  9. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients

    DEFF Research Database (Denmark)

    Győrffy, Balázs; Lánczky, András; Szállási, Zoltán

    2012-01-01

    ). A Kaplan–Meier survival plot was generated and significance was computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature. Of these, CA125 (MUC16; P=3.7x10–5, hazard...... biomarker validation platform that mines all available microarray data to assess the prognostic power of 22 277 genes in 1287 ovarian cancer patients. We specifically used this tool to evaluate the effect of 37 previously published biomarkers on ovarian cancer prognosis....... set up using gene expression data and survival information of 1287 ovarian cancer patients downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (Affymetrix HG-U133A, HG-U133A 2.0, and HG-U133 Plus 2.0 microarrays). After quality control and normalization, only probes present on all...

  10. Intestinal gene expression profiles of piglets benefit from maternal supplementation with a yeast mannan-rich fraction during gestation and lactation.

    Science.gov (United States)

    Graugnard, D E; Samuel, R S; Xiao, R; Spangler, L F; Brennan, K M

    2015-04-01

    The objective was to study the effect of maternal supplementation with a yeast cell wall-based product containing a mannan-rich fraction (MRF) during gestation and lactation on piglet intestinal gene expression. First parity sows were fed experimental gestation and lactation diets with or without MRF (900 mg/kg). After farrowing, piglets were fostered within treatment, as necessary. Sow and litter production performance data were collected until weaning. On day 10 post farrowing, jejunum samples from piglets were collected for gene expression analysis using the Affymetrix Porcine GeneChip array. Most performance parameters did not differ between the treatments. However, protein (Pcolostrum and milk IgG that are essential for development of piglet immune system and gut. In addition, the gene expression patterns affected by the passive immunity transfer showed indicators that could benefit animal performance long term. PMID:25482612

  11. Genome-wide Gene Expression Profiling of SCID Mice with T-cell-mediated Colitis

    DEFF Research Database (Denmark)

    Brudzewsky, D.; Pedersen, A. E.; Claesson, M. H.;

    2009-01-01

    disease. Here, we have investigated severe combined immunodeficient (SCID) mice, which upon adoptive transfer with concanavalin A-activated CD4(+) T cells develop inflammation of the colon with predominance in rectum. Mice with increasing level of inflammation was studied. RNA from rectum of transplanted...... and non-transplanted SCID mice was investigated by a genome-wide gene expression analysis using the Affymetrix mouse expression array 430A (MOE430A) including 22,626 probe sets. A significant change in gene expression (P = 0.00001) is observed in 152 of the genes between the non-transplanted control...... clustering based on the genes with the significantly altered gene expression corresponds to two different levels of inflammation as established by the histological scoring of the inflamed rectum. These data demonstrate that this SCID T-cell transfer model is a useful animal model for human IBD and can be...

  12. A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells.

    Science.gov (United States)

    Lin, Z; Bishop, K S; Sutherland, H; Marlow, G; Murray, P; Denny, W A; Ferguson, L R

    2016-03-01

    Chronic inflammation can lead to the development of cancers and resolution of inflammation is an ongoing challenge. Inflammation can result from dysregulation of the epigenome and a number of compounds that modify the epigenome are in clinical use. In this study the anti-inflammatory and anti-cancer effects of a quinazoline epigenetic-modulator compound were determined in prostate cancer cell lines using a non-hypothesis driven transcriptomics strategy utilising the Affymetrix PrimeView® Human Gene Expression microarray. GATHER and IPA software were used to analyse the data and to provide information on significantly modified biological processes, pathways and networks. A number of genes were differentially expressed in both PC3 and DU145 prostate cancer cell lines. The top canonical pathways that frequently arose across both cell lines at a number of time points included cholesterol biosynthesis and metabolism, and the mevalonate pathway. Targeting of sterol and mevalonate pathways may be a powerful anticancer approach. PMID:26759180

  13. Gene expression profiling of valvular interstitial cells in Rapacz familial hypercholesterolemic swine

    Directory of Open Access Journals (Sweden)

    Ana M. Porras

    2014-12-01

    Full Text Available Rapacz familial hypercholesterolemic (RFH swine is a well-established model of human FH, a highly prevalent hereditary disease associated with increased risk of coronary artery disease and calcific aortic valve disease (CAVD. However, while these animals have been used extensively for the study of atherosclerosis, the heart valves from RFH swine have not previously been examined. We report the analysis of valvular interstitial cell gene expression in adult (two year old and juvenile (three months old RFH and WT swine by microarray analysis via the Affymetrix Porcine Genome Array (GEO #: GSE53997. Principal component and hierarchical clustering analysis revealed grouping and almost no variability between the RFH juvenile and WT juvenile groups. Additionally, only 21 genes were found differentially expressed between these two experimental groups whereas over 900 genes were differentially expressed when comparing either RFH or WT juvenile swine to RFH adults.

  14. Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Reppe, Sjur; Stilgren, Lis; Abrahamsen, Bo;

    2007-01-01

    In primary hyperparathyroidism (PHPT), excess PTH secretion by adenomatous or hyperplastic parathyroid glands leads to elevated serum [Ca(2+)]. Patients present complex symptoms of muscular fatigue, various neuropsychiatric, neuromuscular, and cardiovascular manifestations, and, in advanced disease......, kidney stones and metabolic bone disease. Our objective was to characterize changes in muscle and hematopoietic gene expression in patients with reversible mild PHPT after parathyroidectomy and possibly link molecular pathology to symptoms. Global mRNA profiling using Affymetrix gene chips was carried......,000 expressed genes, 175 muscle, 169 hematological, and 99 bone-associated mRNAs were affected. Notably, the major part of muscle-related mRNAs was increased whereas hematological mRNAs were predominantly decreased during disease. Functional and molecular network analysis demonstrated major alterations of...

  15. Unbalanced three-way chromosomal translocation leading to deletion 18q and duplication 20p.

    Science.gov (United States)

    Oegema, Renske; van Zutven, Laura J C M; van Hassel, Daniella A C M; Huijbregts, Guido C M; Hoogeboom, A Jeannette M

    2012-04-01

    In 1980, a case report on a boy with cleft palate, club feet, dysmorphic features, and developmental delay was published by Bijlsma as a possible distinct syndrome. This case is listed in the London Medical Databases version 1.0. We have reevaluated this patient at adult age. Using high resolution karyotyping and Affymetrix 250k SNP array analysis we identified an unbalanced three-way translocation with breakpoints at 17q22, 18q22.1, and 20p12.2 leading to deletion 18q and duplication 20p. Also, a 715 kb duplication in 1p34.2 and a 245 kb deletion at 1p21.1 were found. Mental retardation, cleft palate, and club feet have repeatedly been reported in deletion 18q patients and therefore we conclude that most of the patient's features can be explained by an 18q deletion. PMID:22406089

  16. Expression profiling of insulin action in human myotubes

    DEFF Research Database (Denmark)

    Hansen, Lars; Gaster, Michael; Oakeley, Edward J;

    2004-01-01

    ), 0.5, 1, 2, 4, 8, and 24 h, mRNA contents were analyzed in human myotubes for each time point using Affymetrix DNA chip technology. Insulin treatment induced an inflammatory and pro-angiogenic response in the myotubes, with expression of early response factors followed by inflammatory chemokines...... diabetic skeletal muscle. We conclude, (i) that insulin induces a time-dependent inflammatory and pro-angiogenic transcriptional response in cultured human myotubes, (ii) that myotubes in vitro retain a gene expression pattern specific for type 2 diabetes and sharing five genes with that of type 2 diabetic......Myotube cultures from patients with type 2 diabetes mellitus (T2DM) represent an experimental in vitro model of T2DM that offers a possibility to perform gene expression studies under standardized conditions. During a time-course of insulin stimulation (1 microM) at 5.5 mM glucose for 0 (no insulin...

  17. Transcriptome response to nitrogen starvation in rice

    Indian Academy of Sciences (India)

    Hongmei Cai; Yongen Lu; Weibo Xie; Tong Zhu; Xingming Lian

    2012-09-01

    Nitrogen is an essential mineral nutrient required for plant growth and development. Insufficient nitrogen (N) supply triggers extensive physiological and biochemical changes in plants. In this study, we used Affymetrix GeneChip rice genome arrays to analyse the dynamics of rice transcriptome under N starvation. N starvation induced or suppressed transcription of 3518 genes, representing 10.88% of the genome. These changes, mostly transient, affected various cellular metabolic pathways, including stress response, primary and secondary metabolism, molecular transport, regulatory process and organismal development. 462 or 13.1% transcripts for N starvation expressed similarly in root and shoot. Comparative analysis between rice and Arabidopsis identified 73 orthologous groups that responded to N starvation, demonstrated the existence of conserved N stress coupling mechanism among plants. Additional analysis of transcription profiles of microRNAs revealed differential expression of miR399 and miR530 under N starvation, suggesting their potential roles in plant nutrient homeostasis.

  18. Insulin-like growth factor I (IGF-I) is a more potent regulator of gene expression than insulin in primary human myoblasts and myotubes

    DEFF Research Database (Denmark)

    Palsgaard, J.; Brown, A.E.; Jensen, M.;

    2009-01-01

    regulation was investigated in primary human skeletal muscle cells before and after differentiation. Cell cultures were treated with 100 nM insulin, IGF-I or nothing for 4h, and gene expression was subsequently determined using the Affymetrix microarray platform. Insulin and IGF-I receptor levels were......Conventionally, insulin is believed to induce a metabolic response, and IGF-I a mitogenic/differentiation response in vivo. However, several studies indicate that the roles of insulin and IGF-I may not be that easy to separate. In this study, insulin and IGF-I specificity in terms of gene......-I receptors as determined by radioligand binding assays. In the myotubes, we did not identify any ligand specificity in terms of functional categories. The major difference between the two ligands was their respective potencies in gene regulation, which was higher for IGF-I than for insulin. This was true for...

  19. Automated SNP Genotype Clustering Algorithm to Improve Data Completeness in High-Throughput SNP Genotyping Datasets from Custom Arrays

    Institute of Scientific and Technical Information of China (English)

    Edward; M.; Smith; Jack; Littrell; Michael; Olivier

    2007-01-01

    High-throughput SNP genotyping platforms use automated genotype calling algo- rithms to assign genotypes. While these algorithms work efficiently for individual platforms, they are not compatible with other platforms, and have individual biases that result in missed genotype calls. Here we present data on the use of a second complementary SNP genotype clustering algorithm. The algorithm was originally designed for individual fluorescent SNP genotyping assays, and has been opti- mized to permit the clustering of large datasets generated from custom-designed Affymetrix SNP panels. In an analysis of data from a 3K array genotyped on 1,560 samples, the additional analysis increased the overall number of genotypes by over 45,000, significantly improving the completeness of the experimental data. This analysis suggests that the use of multiple genotype calling algorithms may be ad- visable in high-throughput SNP genotyping experiments. The software is written in Perl and is available from the corresponding author.

  20. Ascertainment biases in SNP chips affect measures of population divergence

    DEFF Research Database (Denmark)

    Albrechtsen, Anders; Nielsen, Finn Cilius; Nielsen, Rasmus

    2010-01-01

    analyses. However, the single nucleotide polymorphism (SNP) chip data suffer from ascertainment biases caused by the SNP discovery process in which a small number of individuals from selected populations are used as discovery panels. In this study, we investigate the effect of the ascertainment bias on...... inferences regarding genetic differentiation among populations in one of the common genome-wide genotyping platforms. We generate SNP genotyping data for individuals that previously have been subject to partial genome-wide Sanger sequencing and compare inferences based on genotyping data to inferences based...... genotyping calling algorithms can have a surprisingly large effect on population genetic inferences. We not only present a correction of the spectrum for the widely used Affymetrix SNP chips but also show that such corrections are difficult to generalize among studies....

  1. Genotype-dependent Burst of Transposable Element Expression in Crowns of Hexaploid Wheat (Triticum aestivum L. during Cold Acclimation

    Directory of Open Access Journals (Sweden)

    Debbie Laudencia-Chingcuanco

    2012-01-01

    Full Text Available The expression of 1,613 transposable elements (TEs represented in the Affymetrix Wheat Genome Chip was examined during cold treatment in crowns of four hexaploid wheat genotypes that vary in tolerance to cold and in flowering time. The TE expression profiles showed a constant level of expression throughout the experiment in three of the genotypes. In winter Norstar, the most cold-hardy of the four genotypes, a subset of the TEs showed a burst of expression after vernalization saturation was achieved. About 47% of the TEs were expressed, and both Class I (retrotransposons and Class II (DNA transposons types were well represented. Gypsy and Copia were the most represented among the retrotransposons while CACTA and Mariner were the most represented DNA transposons. The data suggests that the Vrn-A1 region plays a role in the stage-specific induction of TE expression in this genotype.

  2. Genomic and proteomic profiling I: Leiomyomas in African Americans and Caucasians

    Directory of Open Access Journals (Sweden)

    Chegini Nasser

    2007-08-01

    Full Text Available Abstract Background Clinical observations indicate that leiomyomas occur more frequently in African Americans compared to other ethnic groups with unknown etiology. To identify the molecular basis for the difference we compared leiomyomas form A. Americans with Caucasians using genomic and proteomic strategies. Methods Microarray, realtime PCR, 2D-PAGE, mass spectrometry, Western blotting and immunohistochemistry. Results Using Affymetrix U133A array and analysis based on P ranking (P Conclusion These findings imply that the level rather than the ethnic-specific expression of a number of genes and proteins may account for the difference between leiomyomas and possibly myometrium, in A. Americans and Caucasians. Further study using larger sample size is required to confirm these findings.

  3. IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Berchtold, L. A.; Larsen, C. M.; Vaag, A.;

    2009-01-01

    Background. We have previously reported that systemic blockade of IL-1 beta in patients with type 2 diabetes with anakinra (a recombinant human interleukin-1-receptor antagonist, IL-1Ra), lowered glycated hemoglobin improved beta-cell function and reduced circulating levels of IL-6 and CRP (7). To...... investigate the effects of IL-1Ra in insulin-sensitive tissue, gene expression levels in skeletal muscle from type 2 diabetic patients treated with IL-1Ra were analysed. Methods. Gene expression profiles in vastus lateralis muscle biopsies from five obese patients (BMI>27) were determined before and after 13...... weeks of treatment with IL-1Ra (anakinra) using Affymetrix U133Plus2.0 GeneChips. Microarray data were normalized and analysed independently using four different algorithms; RMA, GCRMA, dChip and GCOS. Hypothesis tests were applied to the microarray data for each gene, and protein network analysis was...

  4. Emmprin and Survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Andersen, Lars Dyrskjøt; Maase, Hans von der;

    2007-01-01

    PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...... in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin...

  5. Comparison of gene expression and genome-wide DNA methylation profiling between phenotypically normal cloned pigs and conventionally bred controls

    DEFF Research Database (Denmark)

    Fei, Gao; Luo, Yonglun; Li, Shengting;

    2011-01-01

    -specific digital karyotyping (MMSDK) and Solexa sequencing technology. Typical tissue-specific differences with respect to both gene expression and DNA methylation were observed in muscle and liver from cloned as well as control pigs. Gene expression profiles were highly similar between cloned pigs and controls......Animal breeding via Somatic Cell Nuclear Transfer (SCNT) has enormous potential in agriculture and biomedicine. However, concerns about whether SCNT animals are as healthy or epigenetically normal as conventionally bred ones are raised as the efficiency of cloning by SCNT is much lower than natural...... breeding or In-vitro fertilization (IVF). Thus, we have conducted a genome-wide gene expression and DNA methylation profiling between phenotypically normal cloned pigs and control pigs in two tissues (muscle and liver), using Affymetrix Porcine expression array as well as modified methylation...

  6. Prevention of hyperglycemia in Zucker diabetic fatty rats by exercise training: effects on gene expression in insulin-sensitive tissues determined by high-density oligonucleotide microarray analysis

    DEFF Research Database (Denmark)

    Colombo, Michele; Gregersen, Soeren; Kruhoeffer, Mogens;

    2005-01-01

    pancreatic islets after ET in male Zucker diabetic fatty (ZDF) rats. Eighteen ZDF rats (7 weeks old) were divided in a control and ET group. Exercise was performed using a motorized treadmill (20 m/min 1 hour daily for 6 days a week). Blood glucose, weight, and food intake were measured weekly. After 5 weeks......Exercise training (ET) causes metabolic improvement in the prediabetic and diabetic states. However, only little information exists on the changes to ET at the transcriptional level in insulin-sensitive tissues. We have investigated the gene expression changes in skeletal muscle, liver, fat, and......, blood samples, soleus muscle, liver, visceral fat (epididymal fat pads), and islet tissue were collected. Gene expression was quantified with Affymetrix RG-U34A array (16 chips). Exercise training ameliorates the development of hyperglycemia and reduces plasma free fatty acid and the level of glucagon...

  7. Analysis of cell death inducing compounds

    DEFF Research Database (Denmark)

    Spicker, Jeppe; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn;

    2007-01-01

    Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds......), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using the...... three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death in the...

  8. Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas

    DEFF Research Database (Denmark)

    Øster, Bodil; Thorsen, Kasper; Lamy, Philippe;

    2011-01-01

    Resolution Melting (MS-HRM) analysis, and Exon arrays (Affymetrix) the DNA methylation pattern of ~14.000 genes and their transcript levels were investigated in six normal mucosas, six adenomas, and 30 MSI and MSS carcinomas. Sixty eight genes with tumor-specific hypermethylation were identified (p<0.......005). Identified hypermethylated sites were validated in an independent sample set of eight normal mucosas, 12 adenomas, 40 MSS and nine MSI cancer samples. The methylation patterns of 15 selected genes, hypermethylated in adenomas and carcinomas (FLI1, ST6GALNAC5, TWIST1, ADHFE1, JAM2, IRF4, CNRIP1, NRG1, and EYA......, indicating that methylation of these genes may play a direct regulatory role. The hypermethylation changes often occurred already in adenomas, indicating that they may be used as biomarkers for early detection of CRC....

  9. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Nielsen, H S; Moltke, Ida;

    2011-01-01

    Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and...... (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K Xba......I platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3...

  10. Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

    Science.gov (United States)

    Ambra, R; Manca, S; Palumbo, M C; Leoni, G; Natarelli, L; De Marco, A; Consoli, A; Pandolfi, A; Virgili, F

    2014-01-01

    Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG. PMID:24667242

  11. Integration of transcriptomics and metabonomics

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Rantalainen, Mattias; Wang, Yulan;

    2014-01-01

    A systems biology approach to multi-faceted diseases has provided an opportunity to establish a holistic understanding of the processes at play. Thus, the current study merges transcriptomics and metabonomics data in order to improve diagnostics, biomarker identification and to explore the...... possibilities of a molecular phenotyping of ulcerative colitis (UC) patients. Biopsies were obtained from the descending colon of 43 UC patients (22 active UC and 21 quiescent UC) and 15 controls. Genome-wide gene expression analyses were performed using Affymetrix GeneChip Human Genome U133 Plus 2.0. Metabolic...... performance was evaluated using nested Monte Carlo cross-validation. The prediction performance of the merged data sets and that of relative small (<20 variables) multivariate biomarker panels suggest that it is possible to discriminate between active UC, quiescent UC, and controls; between patients with or...

  12. Altered expression of genes involved in mitochondrial oxidative phosphorylation and insulin signaling in skeletal muscle of obese women with polycystic ovary syndrome (PCOS)

    DEFF Research Database (Denmark)

    Skov, Vibe

    similar importance for insulin resistance in the polycystic ovary syndrome (PCOS).   Materials and methods: Using the HG-U133 Plus 2.0 expression array from Affymetrix, we analyzed gene expression in skeletal muscle from obese women with PCOS (n=16) and age- and body mass index-matched control women (n=13...... sum statistic and conducting a permutation test. Subsequently, we performed biological pathway analysis using Gene Set Enrichment Analysis (GSEA) and Gene Microarray Pathway Profiler (GenMAPP).   Results: Women with PCOS were characterized by fasting hyperinsulinemia and impaired insulin...... validated by quantitative real-time PCR and immunoblot analyses.   Conclusion: Our results, for the first time, provide evidence for an association between insulin resistance and impaired mitochondrial oxidative metabolism in skeletal muscle in women with PCOS. Furthermore, differential expression of genes...

  13. Development of an ultra-dense genetic map of the sunflower genome based on single-feature polymorphisms.

    Directory of Open Access Journals (Sweden)

    John E Bowers

    Full Text Available The development of ultra-dense genetic maps has the potential to facilitate detailed comparative genomic analyses and whole genome sequence assemblies. Here we describe the use of a custom Affymetrix GeneChip containing nearly 2.4 million features (25 bp sequences targeting 86,023 unigenes from sunflower (Helianthus annuus L. and related species to test for single-feature polymorphisms (SFPs in a recombinant inbred line (RIL mapping population derived from a cross between confectionery and oilseed sunflower lines (RHA280×RHA801. We then employed an existing genetic map derived from this same population to rigorously filter out low quality data and place 67,486 features corresponding to 22,481 unigenes on the sunflower genetic map. The resulting map contains a substantial fraction of all sunflower genes and will thus facilitate a number of downstream applications, including genome assembly and the identification of candidate genes underlying QTL or traits of interest.

  14. Improved precision and accuracy for microarrays using updated probe set definitions

    Directory of Open Access Journals (Sweden)

    Larsson Ola

    2007-02-01

    Full Text Available Abstract Background Microarrays enable high throughput detection of transcript expression levels. Different investigators have recently introduced updated probe set definitions to more accurately map probes to our current knowledge of genes and transcripts. Results We demonstrate that updated probe set definitions provide both better precision and accuracy in probe set estimates compared to the original Affymetrix definitions. We show that the improved precision mainly depends on the increased number of probes that are integrated into each probe set, but we also demonstrate an improvement when the same number of probes is used. Conclusion Updated probe set definitions does not only offer expression levels that are more accurately associated to genes and transcripts but also improvements in the estimated transcript expression levels. These results give support for the use of updated probe set definitions for analysis and meta-analysis of microarray data.

  15. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen;

    2008-01-01

    Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp....... Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P

  16. TiArA: a virtual appliance for the analysis of Tiling Array data.

    Directory of Open Access Journals (Sweden)

    Jason A Greenbaum

    Full Text Available BACKGROUND: Genomic tiling arrays have been described in the scientific literature since 2003, yet there is a shortage of user-friendly applications available for their analysis. METHODOLOGY/PRINCIPAL FINDINGS: Tiling Array Analyzer (TiArA is a software program that provides a user-friendly graphical interface for the background subtraction, normalization, and summarization of data acquired through the Affymetrix tiling array platform. The background signal is empirically measured using a group of nonspecific probes with varying levels of GC content and normalization is performed to enforce a common dynamic range. CONCLUSIONS/SIGNIFICANCE: TiArA is implemented as a standalone program for Linux systems and is available as a cross-platform virtual machine that will run under most modern operating systems using virtualization software such as Sun VirtualBox or VMware. The software is available as a Debian package or a virtual appliance at http://purl.org/NET/tiara.

  17. RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten Marie; Tan, Qihua; Dahlgaard, Jesper; Kruse, Torben A; Mogensen, Ole

    2007-01-01

    three thaw-freeze cycles. RNA from each aliquot was extracted on the day of division, and quantity and quality were evaluated. RNA from all three aliquots of four tumor samples underwent microarray analysis on Affymetrix Human Genome U133A 2.0 arrays. Microarray data were evaluated using both......Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often...... undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two, and...

  18. Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies

    DEFF Research Database (Denmark)

    Clemmensen, Anders; Thomassen, Mads; Clemmensen, Ole; Tan, Qihua; Kruse, Torben A; Petersen, Thomas K; Andersen, Flemming; Andersen, Klaus E

    2009-01-01

    different incubation times; (ii) the amount and quality of extractable epidermal RNA and (iii) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30-min incubation, the split between dermis and epidermis was not......, and satisfactory amounts of high-quality RNA were obtained. Hybridization to Affymetrix HG_U133A 2.0 GeneChips showed that ammonium thiocyanate incubation had a minute effect on gene expression resulting in only one significantly downregulated gene (cystatin E/M). We conclude that epidermis can be...... reproducibly and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly...

  19. Gene transcripts as potential diagnostic markers for allergic contact dermatitis

    DEFF Research Database (Denmark)

    Hansen, Malene Barré; Skov, Lone; Menné, Torkil;

    2005-01-01

    Affymetrix GeneChip, the gene expression was analysed in PBMC cultures grown with 100 microg/ml CrCl3 or in media alone for 24 hr. A total of 26 genes were differentially expressed by more than twofold (P < 0.01) in allergen-activated PBMCs from patients compared with controls. 18 of these were upregulated......, whereas 8 were downregulated. The expression of 1 downregulated gene, CASP8, was also found specifically and significantly reduced in an expanded population including 4 additional chromium allergic patients and 1 additional control subject by real-time reverse transcriptase polymerase chain reaction (RT......-PCR) analysis. The expression of 2 upregulated genes, ETS2 and CISH, correlated with a high-proliferative response following CrCl3 exposure. Additionally, real-time RT-PCR analysis indicated that the same gene expression changes are valid for nickel allergics, potentially making the expression profile more...

  20. Application of intensity-modulated radiotherapy combined with chemotherapy for the treatment of gastric cancer patients after D1/D2 standard surgery%调强放射治疗并同步化疗在D1/D2标准手术后胃癌治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    李涛; 于长华; 于仁; 朱卫国; 韩济华

    2012-01-01

    Objective: To evaluate the efficacy and complications of concurrent chemoradiotherapy (CCRT) for the treatment of gastric cancer patients after D1/D2 surgery. Methods: Sixty - eight untreated gastric cancer patients (T3/T4 and/or N+ ) were enrolled. They were first treated with surgery,and the clearing scope reached D1/D2 stand-ards with an incisal margin of RO. The patients were randomized into two groups; CCRT group and single chemothera-py group. The CCRT group was treated according to INT 0116 ( Intergroup 0116) . One cycle of chemotherapy consis-ted of 5 - fluorouracil (5 - FU) and tetrahydrogolic acid (LV) administered continuously. CCRT began 28 days after the first cycle of chemotherapy, and the combination of 5 - FU and LV was given in the first four and last three days (corresponding to the second and third cycles of chemotherapy in the single chemotherapy group) during the CCRT period with the radiation dosage of 45Gy/25f,i. e. 1. 8Gy five times per week. Two cycles of the same chemotherapy were administrated one month after radiotherapy - X - ray intensity - modulated external radiation, DT 45Gy/25f. Five cycles of 5 - FU and LV were applied in the single chemotherapy group. Results: One,two and three - year survival rates were 85.9% ,73. 4% and 67.7% in the CCRT group and 68. 0% ,50. 0% and 44. 1% in the single chemotherapy group respectively ( P 0.05) for nausea and vomiting and 70. 6% (24/34) and 44. 1% (15/34) (P<0. 05) for neutrocytopenia. Other indices showed no significant differences. Conclusion; CCRT can increase one,two and three -year total and disease -free survival rates of gastric cancer patients (T3/T4 and/or N+ ) who have been treated with surgery. The major adverse reactions were grade I and II nausea and vomiting,as well as myelosuppression. CCRT is well tolerated.%目的:评价D1/D2手术后胃癌同步放化疗疗效及并发症.方法:68例(T3/T4和(或)N+)胃癌初治患者,手术清扫范围均达到D1/D2

  1. Thermodynamic scaling behavior in genechips

    Directory of Open Access Journals (Sweden)

    Van Hummelen Paul

    2009-01-01

    Full Text Available Abstract Background Affymetrix Genechips are characterized by probe pairs, a perfect match (PM and a mismatch (MM probe differing by a single nucleotide. Most of the data preprocessing algorithms neglect MM signals, as it was shown that MMs cannot be used as estimators of the non-specific hybridization as originally proposed by Affymetrix. The aim of this paper is to study in detail on a large number of experiments the behavior of the average PM/MM ratio. This is taken as an indicator of the quality of the hybridization and, when compared between different chip series, of the quality of the chip design. Results About 250 different GeneChip hybridizations performed at the VIB Microarray Facility for Homo sapiens, Drosophila melanogaster, and Arabidopsis thaliana were analyzed. The investigation of such a large set of data from the same source minimizes systematic experimental variations that may arise from differences in protocols or from different laboratories. The PM/MM ratios are derived theoretically from thermodynamic laws and a link is made with the sequence of PM and MM probe, more specifically with their central nucleotide triplets. Conclusion The PM/MM ratios subdivided according to the different central nucleotides triplets follow qualitatively those deduced from the hybridization free energies in solution. It is shown also that the PM and MM histograms are related by a simple scale transformation, in agreement with what is to be expected from hybridization thermodynamics. Different quantitative behavior is observed on the different chip organisms analyzed, suggesting that some organism chips have superior probe design compared to others.

  2. High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: Four cases of homozygous deletions of the CDKN2A gene

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2008-07-01

    Full Text Available Abstract Background Neuroblastoma is a very heterogeneous pediatric tumor of the sympathetic nervous system showing clinically significant patterns of genetic alterations. Favorable tumors usually have near-triploid karyotypes with few structural rearrangements. Aggressive stage 4 tumors often have near-diploid or near-tetraploid karyotypes and structural rearrangements. Whole genome approaches for analysis of genome-wide copy number have been used to analyze chromosomal abnormalities in tumor samples. We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets. Results Ninety-two neuroblastoma tumors were analyzed with 50 K and/or 250 K SNP arrays from Affymetrix, using CNAG3.0 software. Thirty percent of the tumors harbored 1p deletion, 22% deletion of 11q, 26% had MYCN amplification and 45% 17q gain. Most of the tumors with 1p deletion were found among those with MYCN amplification. Loss of 11q was most commonly seen in tumors without MYCN amplification. In the case of MYCN amplification, two types were identified. One type displayed simple continuous amplicons; the other type harbored more complex rearrangements. MYCN was the only common gene in all cases with amplification. Complex amplification on chromosome 12 was detected in two tumors and three different overlapping regions of amplification were identified. Two regions with homozygous deletions, four cases with CDKN2A deletions in 9p and one case with deletion on 3p (the gene RBMS3 were also detected in the tumors. Conclusion SNP arrays provide useful tools for high-resolution characterization of significant chromosomal rearrangements in neuroblastoma tumors. The mapping arrays from Affymetrix provide both copy number and allele-specific information at a resolution of 10–12 kb. Chromosome 9p, especially the gene

  3. A powerful method for detecting differentially expressed genes from GeneChip arrays that does not require replicates

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    Hein Anne-Mette K

    2006-07-01

    Full Text Available Abstract Background Studies of differential expression that use Affymetrix GeneChip arrays are often carried out with a limited number of replicates. Reasons for this include financial considerations and limits on the available amount of RNA for sample preparation. In addition, failed hybridizations are not uncommon leading to a further reduction in the number of replicates available for analysis. Most existing methods for studying differential expression rely on the availability of replicates and the demand for alternative methods that require few or no replicates is high. Results We describe a statistical procedure for performing differential expression analysis without replicates. The procedure relies on a Bayesian integrated approach (BGX to the analysis of Affymetrix GeneChips. The BGX method estimates a posterior distribution of expression for each gene and condition, from a simultaneous consideration of the available probe intensities representing the gene in a condition. Importantly, posterior distributions of expression are obtained regardless of the number of replicates available. We exploit these posterior distributions to create ranked gene lists that take into account the estimated expression difference as well as its associated uncertainty. We estimate the proportion of non-differentially expressed genes empirically, allowing an informed choice of cut-off for the ranked gene list, adapting an approach proposed by Efron. We assess the performance of the method, and compare it to those of other methods, on publicly available spike-in data sets, as well as in a proper biological setting. Conclusion The method presented is a powerful tool for extracting information on differential expression from GeneChip expression studies with limited or no replicates.

  4. A Brassica exon array for whole-transcript gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Christopher G Love

    Full Text Available Affymetrix GeneChip® arrays are used widely to study transcriptional changes in response to developmental and environmental stimuli. GeneChip® arrays comprise multiple 25-mer oligonucleotide probes per gene and retain certain advantages over direct sequencing. For plants, there are several public GeneChip® arrays whose probes are localised primarily in 3' exons. Plant whole-transcript (WT GeneChip® arrays are not yet publicly available, although WT resolution is needed to study complex crop genomes such as Brassica, which are typified by segmental duplications containing paralogous genes and/or allopolyploidy. Available sequence data were sampled from the Brassica A and C genomes, and 142,997 gene models identified. The assembled gene models were then used to establish a comprehensive public WT exon array for transcriptomics studies. The Affymetrix GeneChip® Brassica Exon 1.0 ST Array is a 5 µM feature size array, containing 2.4 million 25-base oligonucleotide probes representing 135,201 gene models, with 15 probes per gene distributed among exons. Discrimination of the gene models was based on an E-value cut-off of 1E(-5, with ≤98% sequence identity. The 135 k Brassica Exon Array was validated by quantifying transcriptome differences between leaf and root tissue from a reference Brassica rapa line (R-o-18, and categorisation by Gene Ontologies (GO based on gene orthology with Arabidopsis thaliana. Technical validation involved comparison of the exon array with a 60-mer array platform using the same starting RNA samples. The 135 k Brassica Exon Array is a robust platform. All data relating to the array design and probe identities are available in the public domain and are curated within the BrassEnsembl genome viewer at http://www.brassica.info/BrassEnsembl/index.html.

  5. Gene expression profiling in adipose tissue from growing broiler chickens

    Science.gov (United States)

    Hausman, Gary J; Barb, C Rick; Fairchild, Brian D; Gamble, John; Lee-Rutherford, Laura

    2014-01-01

    In this study, total RNA was collected from abdominal adipose tissue samples obtained from ten broiler chickens at 3, 4, 5, and 6 weeks of age and prepared for gene microarray analysis with Affymetrix GeneChip Chicken Genome Arrays (Affymetrix) and quantitative real-time PCR analysis. Studies of global gene expression in chicken adipose tissue were initiated since such studies in many animal species show that adipose tissue expresses and secretes many factors that can influence growth and physiology. Microarray results indicated 333 differentially expressed adipose tissue genes between 3 and 6 wk, 265 differentially expressed genes between 4 and 6 wk and 42 differentially expressed genes between 3 and 4 wk. Enrichment scores of Gene Ontology Biological Process categories indicated strong age upregulation of genes involved in the immune system response. In addition to microarray analysis, quantitative real-time PCR analysis was used to confirm the influence of age on the expression of adipose tissue CC chemokine ligands (CCL), toll-like receptor (TLR)-2, lipopolysaccharide-induced TNF factor (LITAF), chemokine (C-C motif) receptor 8 (CCR8), and several other genes. Between 3 and 6 wk of age CCL5, CCL1, and CCR8 expression increased (P = 0.0001) with age. Furthermore, TLR2, CCL19, and LITAF expression increased between 4 and 6 wk of age (P = 0.001). This is the first demonstration of age related changes in CCL, LITAF, and TLR2 gene expression in chicken adipose tissue. Future studies are needed to elucidate the role of these adipose tissue genes in growth and the immune system. PMID:26317054

  6. Changes in the peripheral blood transcriptome associated with occupational benzene exposure identified by cross-comparison on two microarray platforms

    Energy Technology Data Exchange (ETDEWEB)

    McHale, Cliona M.; Zhang, Luoping; Lan, Qing; Li, Guilan; Hubbard, Alan E.; Forrest, Matthew S.; Vermeulen, Roel; Chen, Jinsong; Shen, Min; Rappaport, Stephen M.; Yin, Songnian; Smith, Martyn T.; Rothman, Nathaniel

    2009-03-01

    Benzene is an established cause of leukemia and a possible cause of lymphoma in humans but the molecular pathways underlying this remain largely undetermined. This study sought to determine if the use of two different microarray platforms could identify robust global gene expression and pathway changes associated with occupational benzene exposure in the peripheral blood mononuclear cell (PBMC) gene expression of a population of shoe-factory workers with well-characterized occupational exposures to benzene. Microarray data was analyzed by a robust t-test using a Quantile Transformation (QT) approach. Differential expression of 2692 genes using the Affymetrix platform and 1828 genes using the Illumina platform was found. While the overall concordance in genes identified as significantly associated with benzene exposure between the two platforms was 26% (475 genes), the most significant genes identified by either array were more likely to be ranked as significant by the other platform (Illumina = 64%, Affymetrix = 58%). Expression ratios were similar among the concordant genes (mean difference in expression ratio = 0.04, standard deviation = 0.17). Four genes (CXCL16, ZNF331, JUN and PF4), which we previously identified by microarray and confirmed by real-time PCR, were identified by both platforms in the current study and were among the top 100 genes. Gene Ontology analysis showed over representation of genes involved in apoptosis among the concordant genes while Ingenuity{reg_sign} Pathway Analysis (IPA) identified pathways related to lipid metabolism. Using a two-platform approach allows for robust changes in the PBMC transcriptome of benzene-exposed individuals to be identified.

  7. Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis

    Science.gov (United States)

    Gamper, Marianne; Viereck, Volker; Geissbühler, Verena; Eberhard, Jakob; Binder, Jochen; Moll, Carlo; Rehrauer, Hubert; Moser, René

    2009-01-01

    Background Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Results Gene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix – GeneChip® Human Genome U133 Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection p-value < 0.05). The difference between the two groups was significant for over 3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression ratio greater than two. The IC pattern had similarities to patterns from immune system, lymphatic, and autoimmune diseases. The dominant biological processes were the immune and inflammatory responses. Many of the up-regulated genes were expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall is a dominant feature of ulcerative IC. Histopathological data supported these findings. Conclusion GeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC) will further indicate whether the data presented here will be valuable for the diagnosis of IC. PMID:19400928

  8. From hybridization theory to microarray data analysis: performance evaluation

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    Berger Fabrice

    2011-12-01

    Full Text Available Abstract Background Several preprocessing methods are available for the analysis of Affymetrix Genechips arrays. The most popular algorithms analyze the measured fluorescence intensities with statistical methods. Here we focus on a novel algorithm, AffyILM, available from Bioconductor, which relies on inputs from hybridization thermodynamics and uses an extended Langmuir isotherm model to compute transcript concentrations. These concentrations are then employed in the statistical analysis. We compared the performance of AffyILM and other traditional methods both in the old and in the newest generation of GeneChips. Results Tissue mixture and Latin Square datasets (provided by Affymetrix were used to assess the performances of the differential expression analysis depending on the preprocessing strategy. A correlation analysis conducted on the tissue mixture data reveals that the median-polish algorithm allows to best summarize AffyILM concentrations computed at the probe-level. Those correlation results are equivalent to the best correlations observed using popular preprocessing methods relying on intensity values. The performances of each tested preprocessing algorithm were quantified using the Latin Square HG-U133A dataset, thanks to the comparison of differential analysis results with the list of spiked genes. The figures of merit generated illustrates that the performances associated to AffyILM(medianpolish, inferred from the present statistical analysis, are comparable to the best performing strategies previously reported. Conclusions Converting probe intensities to estimates of target concentrations prior to the statistical analysis, AffyILM(medianpolish is one of the best performing strategy currently available. Using hybridization theory, probe-level estimates of target concentrations should be identically distributed. In the future, a probe-level multivariate analysis of the concentrations should be compared to the univariate analysis of

  9. Genome wide analysis of differentially expressed genes in HK-2 cells, a line of human kidney epithelial cells in response to oxalate.

    Directory of Open Access Journals (Sweden)

    Sweaty Koul

    Full Text Available Nephrolithiasis is a multi-factorial disease which, in the majority of cases, involves the renal deposition of calcium oxalate. Oxalate is a metabolic end product excreted primarily by the kidney. Previous studies have shown that elevated levels of oxalate are detrimental to the renal epithelial cells; however, oxalate renal epithelial cell interactions are not completely understood. In this study, we utilized an unbiased approach of gene expression profiling using Affymetrix HG_U133_plus2 gene chips to understand the global gene expression changes in human renal epithelial cells [HK-2] after exposure to oxalate. We analyzed the expression of 47,000 transcripts and variants, including 38,500 well characterized human genes, in the HK2 cells after 4 hours and 24 hours of oxalate exposure. Gene expression was compared among replicates as per the Affymetrix statistical program. Gene expression among various groups was compared using various analytical tools, and differentially expressed genes were classified according to the Gene Ontology Functional Category. The results from this study show that oxalate exposure induces significant expression changes in many genes. We show for the first time that oxalate exposure induces as well as shuts off genes differentially. We found 750 up-regulated and 2276 down-regulated genes which have not been reported before. Our results also show that renal cells exposed to oxalate results in the regulation of genes that are associated with specific molecular function, biological processes, and other cellular components. In addition we have identified a set of 20 genes that is differentially regulated by oxalate irrespective of duration of exposure and may be useful in monitoring oxalate nephrotoxicity. Taken together our studies profile global gene expression changes and provide a unique insight into oxalate renal cell interactions and oxalate nephrotoxicity.

  10. Serum MicroRNA-4521 is a Potential Biomarker for Focal Cortical Dysplasia with Refractory Epilepsy.

    Science.gov (United States)

    Wang, Xiaofeng; Sun, Yuqiang; Tan, Zeshi; Che, Ningwei; Ji, Anlong; Luo, Xiaodong; Sun, Xu; Li, Xinyu; Yang, Kang; Wang, Guanyu; Luan, Lan; Liu, Yaoling; Wei, Minghai; Yin, Jian

    2016-04-01

    Early biomarker-based diagnosis of focal cortical dysplasia (FCD) represents a major clinical challenge. The aim of this study was to identify novel brain microRNAs (miRNAs) in patients with refractory epilepsy and FCD as potential biomarkers. We evaluated serum hsa-miR-4521 as a promising novel biomarker in patients with FCD. Tissue for microarray was obtained from nine patients with temporal lobe refractory epilepsy who underwent surgery to remove epileptic foci identified by cortical video electroencephalogram monitoring. Control tissue was collected from eight patients with hypertension who required emergency surgery to remove an intracranial hematoma. The Affymetrix(®) GeneChip(®) Command Console(®) Software (Affymetrix miRNA 4.0) was used to compare miRNA expression in the cerebral cortex of experimental and control patients. Temporal cortex tissue and serum samples were taken from the same patients for verification of hsa-miR-4521 expression by real-time quantitative polymerase chain reaction (RT-qPCR). The experimental and control patients did not differ significantly in terms of age and gender. 19.4 % (148/764) of the total miRNAs were differentially expressed in experimental and control tissue, which is in agreement with the existing literature. We selected miRNA-4521 for further analysis; the fold-change in expression was 14.4707 and the q value was almost 0, which confirmed up-regulation. Significant up-regulation of hsa-miR-4521 was further validated by RT-qPCR. miRNA microarrays can efficiently and conveniently identify differentially expressed miRNAs in epilepsy brain tissue. This is the first study to identify differential expression of hsa-miR-4521 in brain tissue and serum of refractory epilepsy patients and suggests that serum hsa-miR-4521 may represent a potential diagnostic biomarker for FCD with refractory epilepsy. PMID:26645999

  11. Highly expressed genes are associated with inverse antisense transcription in mouse

    Indian Academy of Sciences (India)

    Andras Györffy; Pawel Surowiak; Zsolt Tulassay; Balazs Györffy

    2007-08-01

    There is a growing evidence, that antisense transcription might have a key role in a range of human diseases. Although predefined sense–antisense pairs were extensively studied, the antisense expression of the known sense genes is rarely investigated. We retrieved and correlated the expression of sense and antisense sequences of 1182 mouse transcripts to assess the prevalence and to find the characteristic pattern of antisense transcription. We contrasted three Affymetrix MGU74A version 1 mouse genome chips to six MGU74A version 2 chips. For these 1182 transcripts, the version 1 chips contain the antisense sequences of the transcripts presented on the version 2 chips. The original data was taken from the GEO database (GDS431 and GDS432). As the Affymetrix data are semiquantitative, the relative expression levels of antisense partners were analysed. We detected antisense transcription, although the average antisense expression is shifted towards smaller expression values (MGU74A version 1, 516; version 2, 1688). An inverse direct correlation between sense and antisense expression values could be observed at high expression values. At a very high relative expression—above 40,000—the Pearson correlation coefficient is getting closer to −1. Transcripts with high inverse expression ratio may be correlated to the investigated gene (major histocompatibility complex class II trans activator). The ratio of sense to antisense transcripts varied among different chromosomes; on chromosomes 14 and 1 the level of antisense expression was higher than that of sense. We conclude that antisense transcription is a common phenomenon in the mouse genome. The hypothesis of regulatory role of antisense transcripts is supported by the inverse antisense gene expression of highly expressed genes.

  12. A meta-analysis of kidney microarray datasets: investigation of cytokine gene detection and correlation with rt-PCR and detection thresholds

    Directory of Open Access Journals (Sweden)

    Stegall Mark D

    2007-03-01

    Full Text Available Abstract Background Microarrays provide a means to simultaneously examine the gene expression of the entire transcriptome in a single sample. Many studies have highlighted the need for novel software and statistical approaches to assess the measured gene expression. Less attention has been directed toward whether genes considered undetectable by microarray can be detected by other strategies or whether these genes can provide accurate gene expression determinations. In the kidney this is a concern for genes such as cytokines which dramatically influence the immune response but are often considered low abundance genes produced by a small number of cells. Results Using both publicly available and our own microarray datasets we analyzed the detection p-value and detection call values for 81 human kidney samples run on the U133A or U133Plus2.0 Affymetrix microarrays (Affymetrix, Santa Clara, CA. For the cytokine genes, the frequency of detection in each sample group (normal, transplant and renal cell carcinoma was examined and revealed that a majority of cytokine related genes are not detectable in human kidney by microarray. Using a subset of 29 Mayo transplant samples, a group of seven transplant-related cytokines and eight non-cytokine genes were evaluated by real-time PCR (rt-PCR. For these 15 genes we compared the impact of decreasing microarray detection frequency with the changes in gene expression observed by both microarray and rt-PCR. We found that as microarray detection frequency decreased the correlation between microarray and rt-PCR data also decreased. Conclusion We conclude that, when analyzing microarray data from human kidney samples, genes generally expressed at low abundance (i.e. cytokines should be evaluated with more sensitive approaches such as rt-PCR. In addition, our data suggest that the use of detection frequency cutoffs for inclusion or exclusion of microarray data may be appropriate when comparing microarray and rt

  13. The removal of multiplicative, systematic bias allows integration of breast cancer gene expression datasets – improving meta-analysis and prediction of prognosis

    Directory of Open Access Journals (Sweden)

    Pepper Stuart D

    2008-09-01

    Full Text Available Abstract Background The number of gene expression studies in the public domain is rapidly increasing, representing a highly valuable resource. However, dataset-specific bias precludes meta-analysis at the raw transcript level, even when the RNA is from comparable sources and has been processed on the same microarray platform using similar protocols. Here, we demonstrate, using Affymetrix data, that much of this bias can be removed, allowing multiple datasets to be legitimately combined for meaningful meta-analyses. Results A series of validation datasets comparing breast cancer and normal breast cell lines (MCF7 and MCF10A were generated to examine the variability between datasets generated using different amounts of starting RNA, alternative protocols, different generations of Affymetrix GeneChip or scanning hardware. We demonstrate that systematic, multiplicative biases are introduced at the RNA, hybridization and image-capture stages of a microarray experiment. Simple batch mean-centering was found to significantly reduce the level of inter-experimental variation, allowing raw transcript levels to be compared across datasets with confidence. By accounting for dataset-specific bias, we were able to assemble the largest gene expression dataset of primary breast tumours to-date (1107, from six previously published studies. Using this meta-dataset, we demonstrate that combining greater numbers of datasets or tumours leads to a greater overlap in differentially expressed genes and more accurate prognostic predictions. However, this is highly dependent upon the composition of the datasets and patient characteristics. Conclusion Multiplicative, systematic biases are introduced at many stages of microarray experiments. When these are reconciled, raw data can be directly integrated from different gene expression datasets leading to new biological findings with increased statistical power.

  14. In vitro identification and in silico utilization of interspecies sequence similarities using GeneChip® technology

    Directory of Open Access Journals (Sweden)

    Ye Shui Q

    2005-05-01

    Full Text Available Abstract Background Genomic approaches in large animal models (canine, ovine etc are challenging due to insufficient genomic information for these species and the lack of availability of corresponding microarray platforms. To address this problem, we speculated that conserved interspecies genetic sequences can be experimentally detected by cross-species hybridization. The Affymetrix platform probe redundancy offers flexibility in selecting individual probes with high sequence similarities between related species for gene expression analysis. Results Gene expression profiles of 40 canine samples were generated using the human HG-U133A GeneChip (U133A. Due to interspecies genetic differences, only 14 ± 2% of canine transcripts were detected by U133A probe sets whereas profiling of 40 human samples detected 49 ± 6% of human transcripts. However, when these probe sets were deconstructed into individual probes and examined performance of each probe, we found that 47% of human probes were able to find their targets in canine tissues and generate a detectable hybridization signal. Therefore, we restricted gene expression analysis to these probes and observed the 60% increase in the number of identified canine transcripts. These results were validated by comparison of transcripts identified by our restricted analysis of cross-species hybridization with transcripts identified by hybridization of total lung canine mRNA to new Affymetrix Canine GeneChip®. Conclusion The experimental identification and restriction of gene expression analysis to probes with detectable hybridization signal drastically increases transcript detection of canine-human hybridization suggesting the possibility of broad utilization of cross-hybridizations of related species using GeneChip technology.

  15. A multicenter, cross-platform clinical validation study of cancer cytogenomic arrays.

    Science.gov (United States)

    Li, Marilyn M; Monzon, Federico A; Biegel, Jaclyn A; Jobanputra, Vaidehi; Laffin, Jennifer J; Levy, Brynn; Leon, Annette; Miron, Patricia; Rossi, Michael R; Toruner, Gokce; Alvarez, Karla; Doho, Gregory; Dougherty, Margaret J; Hu, Xiaofeng; Kash, Shera; Streck, Deanna; Znoyko, Iya; Hagenkord, Jill M; Wolff, Daynna J

    2015-11-01

    Cytogenomic microarray analysis (CMA) offers high resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multiplatform, multicenter clinical validation project to compare the reliability and inter- and intralaboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms-from Affymetrix, Agilent, and Illumina. Each microarray platform was employed at two independent test sites. The results were compared in a blinded manner with current standard methods, including karyotype, FISH, or morphology. Twenty-nine chronic lymphocytic leukemia blood, 34 myelodysplastic syndrome bone marrow, and 30 fresh frozen renal epithelial tumor samples were assessed by all six laboratories. Thirty formalin fixed paraffin embedded renal tumor samples were analyzed at the Affymetrix and Agilent test sites only. All study samples were initial diagnostic samples. Array data were analyzed at each participating site and were submitted to caArray for central analysis. Laboratory interpretive results were submitted to the central analysis team for comparison with the standard-of-care assays and for calculation of intraplatform reproducibility and cross-platform concordance. The results demonstrated that the three microarray platforms 1) detect clinically actionable genomic changes in cancer compatible to standard-of-care methods; 2) further define cytogenetic aberrations; 3) identify submicroscopic alterations and loss of heterozygosity (LOH); and 4) yield consistent results within and between laboratories. Based on this study, the CGC concludes that CMA is a sensitive and reliable technique for copy number and LOH assessment that may be used for clinical oncology genomic analysis. PMID:26454669

  16. The periparturient period is associated with structural and transcriptomic adaptations of rumen papillae in dairy cattle.

    Science.gov (United States)

    Steele, M A; Schiestel, C; AlZahal, O; Dionissopoulos, L; Laarman, A H; Matthews, J C; McBride, B W

    2015-04-01

    The structural and functional adaption of the rumen epithelium during the transition period is largely undescribed. To characterize the adaptation of the rumen epithelium during transition, multiparous dairy cattle (n=12) fitted with rumen fistulas and fed a low-energy dry cow diet (1.37 Mcal/kg, net energy for lactation) were transitioned abruptly to a high-energy lactating cow diet (1.68 Mcal/kg, net energy for lactation) immediately after parturition. Rumen papillae were biopsied at -3, +1, and +6 wk relative to calving. The histology of morphology of the rumen papillae was evaluated under the light microscope and electron microscope, and mRNA profiling was performed using an Affymetrix GeneChip Bovine Gene 1.0 ST Array (Affymetrix, Santa Clara, CA). Data preprocessing was conducted using the robust multi-array average method, and detection of significant genes was conducted using ANOVA. Also, the Benjamini-Hochberg false discovery rate of 0.1 was applied. Microscopic examination of rumen papillae revealed an increase in epithelial desquamation during early lactation as sloughing scores increased from 1.7 ± 0.2 at -3 wk to 4.1 ± 0.3 and 3.4 ± 0.2 at +1 and + 6 wk, respectively. A total of 1,011 (-3 vs. +1 wk) and 729 (-3 vs. +6 wk) differentially expressed genes were identified (false discovery rate of 0.10, Ptransition period in dairy cattle. In conclusion, the experimental data support the hypothesis that rumen papillae adapt in early lactation by altering their gene expression patterns and, thus, their epithelial structure. PMID:25682143

  17. GECKO: a complete large-scale gene expression analysis platform

    Directory of Open Access Journals (Sweden)

    Heuer Michael

    2004-12-01

    Full Text Available Abstract Background Gecko (Gene Expression: Computation and Knowledge Organization is a complete, high-capacity centralized gene expression analysis system, developed in response to the needs of a distributed user community. Results Based on a client-server architecture, with a centralized repository of typically many tens of thousands of Affymetrix scans, Gecko includes automatic processing pipelines for uploading data from remote sites, a data base, a computational engine implementing ~ 50 different analysis tools, and a client application. Among available analysis tools are clustering methods, principal component analysis, supervised classification including feature selection and cross-validation, multi-factorial ANOVA, statistical contrast calculations, and various post-processing tools for extracting data at given error rates or significance levels. On account of its open architecture, Gecko also allows for the integration of new algorithms. The Gecko framework is very general: non-Affymetrix and non-gene expression data can be analyzed as well. A unique feature of the Gecko architecture is the concept of the Analysis Tree (actually, a directed acyclic graph, in which all successive results in ongoing analyses are saved. This approach has proven invaluable in allowing a large (~ 100 users and distributed community to share results, and to repeatedly return over a span of years to older and potentially very complex analyses of gene expression data. Conclusions The Gecko system is being made publicly available as free software http://sourceforge.net/projects/geckoe. In totality or in parts, the Gecko framework should prove useful to users and system developers with a broad range of analysis needs.

  18. Measuring enjoyable informal learning using augmented reality at cultural heritage site

    Science.gov (United States)

    Pendit, Ulka Chandini; Zaibon, Syamsul Bahrin; Bakar, Juliana Aida Abu

    2016-08-01

    The instrument of evaluation of measuring enjoyable informal learning at cultural heritage site was produced by validity and reliability analysis. It involved two cycles of steps, content validity and face validity and content validity and reliability analysis. From the analysis, it was found out that the instrument is reliable to be measure enjoyable informal learning at cultural heritage site.

  19. Understanding the Early Years: Early Childhood Development in the Montreal Study Area, Montreal, Quebec. An Analysis of the Communities Survey

    Science.gov (United States)

    Xu, Gong-Li; Ahmed, Nina; Abbes, Chahreddine

    2010-01-01

    This report presents survey findings from two cycles of data collection in a 45-km area of Montreal located east of the city centre. The study was conducted by Statistics Canada as part of the second pilot phase of the Understanding the Early Years initiative (UEY-II), using the Communities Survey, a research tool adapted from the National…

  20. The Development of a Cognitive Tool for Teaching and Learning Fractions in the Mathematics Classroom: A Design-Based Study

    Science.gov (United States)

    Kong, S. C.

    2008-01-01

    Two cycles of design-based research of a cognitive tool (CT) for teaching fractions have been completed. Following the success of a quasi-experimental study of the enhanced CT derived from the second cycle of design-based research, this article reports the findings of a pre-test-post-test control group empirical study using the enhanced CT in the…

  1. Are Physical Education-Related State Policies and Schools' Physical Education Requirement Related to Children's Physical Activity and Obesity?

    Science.gov (United States)

    Kim, Jinsook

    2012-01-01

    Background: This study examines whether the extent of states' physical education (PE) requirement policies and the prevalence of schools requiring PE are associated with children's physical activity (PA) and obesity. Methods: Two cycles (2002-2003 and 2006-2007) of cross-sectional data with individual- and state-level information were…

  2. Sometimes "Newton's Method" Always "Cycles"

    Science.gov (United States)

    Latulippe, Joe; Switkes, Jennifer

    2012-01-01

    Are there functions for which Newton's method cycles for all non-trivial initial guesses? We construct and solve a differential equation whose solution is a real-valued function that two-cycles under Newton iteration. Higher-order cycles of Newton's method iterates are explored in the complex plane using complex powers of "x." We find a class of…

  3. 75 FR 24824 - Energy Efficiency Program for Consumer Products: Public Meeting and Availability of the Framework...

    Science.gov (United States)

    2010-05-06

    ...; (3) product price; (4) life-cycle cost (LCC) and payback period (PBP); (5) national impacts analysis... Refrigerators, Freezers, and Refrigerator- Freezers. The final rule was published on January 9, 2009. (74 FR 1091). The EPACT 2005 amendments to EPCA also require DOE to conduct two cycles of rulemakings...

  4. Some heuristics and results for small cycles of the discrete logarithm.

    NARCIS (Netherlands)

    J. Holden; P. Moree

    2006-01-01

    Abstract: Brizolis asked the question: does every prime p have a pair (g,h) such that h is a fixed point for the discrete logarithm with base g? The first author previously extended this question to ask about not only fixed points but also two-cycles, and gave heuristics (building on work of Zhang,

  5. Getting Girls in the Game: Action Research in the Gymnasium

    Science.gov (United States)

    Robinson, Daniel B.

    2013-01-01

    This article presents an action research project focused on improving physical education (PE) for adolescent female students. One university researcher, three male PE teachers, and 13 of their most disengaged female students participated in the one-year, two-cycle, action research project. The process and results are offered so that future PE…

  6. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2009-01-01

    Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear…

  7. Differential Selection into Secondary Schools in Serbia

    Science.gov (United States)

    Baucal, Aleksandar; Pavlovic-Babic, Dragica; Willms, J. Douglas

    2006-01-01

    In Serbia there are four levels of education: pre-school (until 7 years of age); primary education consisting of eight grades (ages 7-14); secondary education lasting two, three or four years; and higher education lasting from three to six years. Primary education is compulsory for all children. It consists of two cycles, each lasting four years,…

  8. Classification of networks of automata by dynamical mean field theory

    International Nuclear Information System (INIS)

    Dynamical mean field theory is used to classify the 224=65,536 different networks of binary automata on a square lattice with nearest neighbour interactions. Application of mean field theory gives 700 different mean field classes, which fall in seven classes of different asymptotic dynamics characterized by fixed points and two-cycles. (orig.)

  9. Spectral characterizations of propeller graphs

    OpenAIRE

    Liu, Xiaogang; Zhou, Sanming

    2012-01-01

    A propeller graph is obtained from an $\\infty$-graph by attaching a path to the vertex of degree four, where an $\\infty$-graph consists of two cycles with precisely one common vertex. In this paper, we prove that all propeller graphs are determined by their Laplacian spectra as well as their signless Laplacian spectra.

  10. The ovulation pattern during three consecutive menstrual cycles has a significant impact on pregnancy rate and sex of the offspring

    DEFF Research Database (Denmark)

    Fukuda, Misao; Fukuda, Kiyomi; Tatsumi, Kenichi;

    2011-01-01

    left-left-left of left-sided ovulation. Our data suggest that IVF and IUI treatment in cycles in which development of the preovulatory follicle(s) occurs in the right-sided ovary-and ovulations took place from the left-sided ovary in the preceding two cycles (left-left-right)-is likely to show the best...

  11. Learning to Love Reading: A Self-Study on Fostering Students' Reading Motivation in Small Groups

    Science.gov (United States)

    Miller, Rosa

    2015-01-01

    This study explores the relationship between small, differentiated reading groups and fourth-grade students' reading motivation. Using self-study methodology, the author examined her own process of implementing these reading groups through two cycles of action research. Data were analyzed from two different administrations of the Motivations for…

  12. Large amplitude electromagnetic solitons in intense laser plasma interaction

    Institute of Scientific and Technical Information of China (English)

    Li Bai-Wen; Ishiguro S; Skoric M M

    2006-01-01

    This paper shows that the standing, backward- and forward-accelerated large amplitude relativistic electromagnetic solitons induced by intense laser pulse in long underdense collisionless homogeneous plasmas can be observed by particle simulations. In addition to the inhomogeneity of the plasma density, the acceleration of the solitons also depends upon not only the laser amplitude but also the plasma length. The electromagnetic frequency of the solitons is between about half and one of the unperturbed electron plasma frequency. The electrostatic field inside the soliton has a one-cycle structure in space, while the transverse electric and magnetic fields have half-cycle and one-cycle structure respectively.Analytical estimates for the existence of the solitons and their electromagnetic frequencies qualitatively coincide with our simulation results.

  13. Consistency and Derangements in Brane Tilings

    CERN Document Server

    Hanany, Amihay; Ramgoolam, Sanjaye; Seong, Rak-Kyeong

    2015-01-01

    Brane tilings describe Lagrangians (vector multiplets, chiral multiplets, and the superpotential) of four dimensional $\\mathcal{N}=1$ supersymmetric gauge theories. These theories, written in terms of a bipartite graph on a torus, correspond to worldvolume theories on $N$ D$3$-branes probing a toric Calabi-Yau threefold singularity. A pair of permutations compactly encapsulates the data necessary to specify a brane tiling. We show that geometric consistency for brane tilings, which ensures that the corresponding quantum field theories are well behaved, imposes constraints on the pair of permutations, restricting certain products constructed from the pair to have no one-cycles. Permutations without one-cycles are known as derangements. We illustrate this formulation of consistency with known brane tilings. Counting formulas for consistent brane tilings with an arbitrary number of chiral bifundamental fields are written down in terms of delta functions over symmetric groups.

  14. Integration of diffusion weighted MRI data and a simple mathematical model to predict breast tumor cellularity during neoadjuvant chemotherapy

    OpenAIRE

    Atuegwu, Nkiruka C.; Arlinghaus, Lori R.; Li, Xia; BrianWelch, E.; Chakravarthy, Bapsi A.; John C Gore; Yankeelov, Thomas E.

    2011-01-01

    Diffusion-weighted magnetic resonance imaging (DW-MRI) data obtained early in the course of therapy can be used to estimate tumor proliferation rates, and the estimated rates can be used to predict tumor cellularity at the conclusion of therapy. Six patients underwent DW-MRI immediately before, after one cycle, and after all cycles of neoadjuvant chemotherapy. Apparent diffusion coefficient (ADC) values were calculated for each voxel and for a whole tumor region of interest (ROI). Proliferati...

  15. Increased Fertilization Rates after In Vitro Culture of Frozen-Thawed Testicular Immotile Sperm in Nonobstructive Azoospermic Patients

    OpenAIRE

    Nuñez-Calonge, R.; Cortes, S; Gago, M.; López, P.; Caballero-Peregrin, P.

    2012-01-01

    Objective. To optimise the use of freeze/thaw testicular immotile spermatozoa from nonobstructive azoospermia patients and to analyse the outcome of intracytoplasmic sperm injection (ICSI) of such spermatozoa. Methods. Testicular specimens were retrieved and cryopreserved from forty patients with nonobstructive azoospermia and underwent one cycle with thawed spermatozoa (Group I) that led to pregnancy in sixteen cases. Twenty-four patients of group I underwent treatment with the same batch of...

  16. Sample-based engine noise synthesis using an enhanced pitch-synchronous overlap-and-add method

    OpenAIRE

    Jagla, Jan; Maillard, Julien; Martin, Nadine

    2012-01-01

    An algorithm for the real time synthesis of internal combustion engine noise is presented. Through the analysis of a recorded engine noise signal of continuously varying engine speed, a dataset of sound samples is extracted allowing the real time synthesis of the noise induced by arbitrary evolutions of engine speed. The sound samples are extracted from a recording spanning the entire engine speed range. Each sample is delimitated such as to contain the sound emitted during one cycle of the e...

  17. Solid-state logic equipment for ultrasound periodic inspections of reactor pressure vessels

    International Nuclear Information System (INIS)

    Solid-state logic equipment is described for periodic ultrasonic inspection of power reactor pressure vessels. The equipment block diagram is shown. The equipment can use different types of measuring heads comprising up to 12 probes and 46 steps in one measuring cycle. The duration of one step is 250 microseconds and one cycle lasts 12.5 milliseconds. Both direct and indirect echoes can be processed depending on a preset algorithm. (Ha)

  18. Hexagonal and honeycomb structures in Dielectric Barrier Discharges

    OpenAIRE

    Bernecker, B; Callegari, T; S. Blanco; Fournier, R.; Boeuf, J P

    2009-01-01

    Abstract We present an experimental study of pattern formation in a Dielectric Barrier Discharge in Neon at 100 torr and 1 mm gap. An intensified CCD camera is used to analyze the time evolution of the patterns during one cycle of the voltage waveform. The formation of a hexagonal pattern of filaments in a transient, glow-like regime is observed, followed by a honeycomb structure that corresponds to a Townsend discharge occurring outside the regions delimite...

  19. Overview of the use of ethanolamine in Mihama Unit 2

    International Nuclear Information System (INIS)

    To reduce iron ingress into a steam generator (SG) in an effort toward maintaining SG long-term integrity in the PWR secondary system, ethanolamine (ETA) optimum concentration test and assessment after one cycle operation with ETA treatment were conducted at Mihama Unit 2. As a result, iron concentration was reduced approximately 50% and 85% at the feedwater and the moisture separator drains respectively, with no observed negative impact on secondary water chemistry, condensate polisher resin, and secondary piping and components. (author)

  20. A novel soft switching crossing current resonant converter (XCRC)

    OpenAIRE

    Poon, FNK; Pong, MH

    1994-01-01

    Unlike other resonate or soft-switching converter, this novel topology employs only two switches and a very simply control method. The inherent constant power protection feature is another merit. No special resonate chip is needed to control the circuit. By adding two diode parallel with the dividing capacitors and selecting the capacitors for a small value that will fully charge and discharge in one cycle, one can obtain the zero voltage switching characteristic and control the output voltag...

  1. Taxol arrests the development of blood-stage Plasmodium falciparum in vitro and Plasmodium chabaudi adami in malaria-infected mice.

    OpenAIRE

    Pouvelle, B; Farley, P J; Long, C A; Taraschi, T.F.

    1994-01-01

    Taxol, a natural product used to treat a variety of human cancers, is shown here to be extremely effective against chloroquine- and pyrimethamine-resistant malaria parasites. Addition of Taxol (1.0 microM) for one cycle to cultures of human erythrocytes infected with Plasmodium falciparum prevents the establishment of new infections. Blood parasitemia is eliminated in mice infected with Plasmodium chabaudi adami when they are given a single intraperitoneal injection of Taxol at 150 mg/m2. The...

  2. Sedimentation and Tectonics of Zenisu Ridge, Eastern Nankai Trough and Suruga Trough Regions

    OpenAIRE

    Shimamura, Kiyoshi

    1988-01-01

    Great amounts of terrigenous sediments have been deposited as trough wedge sedimentary layers in the Suruga Trough and the Eastern Nankai Trough since the late Pliocene. Trough wedge sedimentary layers show some cyclic sedimentation correlating with the block collision. The cycle has originated from an intence uplift of land with the block collision and ended in the deformation of trough-fill layers with the plate subduction. In one cycle, an unconformity has been formed in the region around ...

  3. Detection of Fault Location in Transmission Lines using Wavelet Transform

    OpenAIRE

    Shilpi Sahu

    2013-01-01

    This paper presents a technique to detect the location of the different faults on a transmission lines for quick and reliable operation of protection schemes. The simulation is developed in MATLAB to generate the fundamental component of the transient voltage and current simultaneously both in time and frequency domain. One cycle of waveform, covering pre-fault and post-fault information is abstracted for analysis. The discrete wavelet transform (DWT) is used for data preprocessing. It is app...

  4. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

    OpenAIRE

    Alina Tudorica; Oh, Karen Y.; Stephen Y-C Chui; Nicole Roy; Troxell, Megan L.; Arpana Naik; Kathleen A Kemmer; Yiyi Chen; Megan L Holtorf; Aneela Afzal; Charles S Springer Jr.; Xin Li; Wei Huang

    2016-01-01

    The purpose is to compare quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT) and evaluation of residual cancer burden (RCB). Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Eval...

  5. Bacterial communities associated with white shrimp (Litopenaeus vannamei) larvae at early developmental stages

    OpenAIRE

    ANTONIUS SUWANTO; YULIN LESTARI; MAGGY TENNAWIJAYA SUHARTONO; ARTINI PANGASTUTI

    2010-01-01

    Bacterial communities associated with white shrimp (Litopenaeus vannamei) larvae at early developmental stages. Biodiversitas 11 (2): 65-68.Terminal Restriction Fragment Length Polymorphism (T-RFLP) was used to monitor the dynamics of the bacterial communities associated with early developmental stages of white shrimp (Litopenaeus vannamei) larvae. Samples for analysis were egg, hatching nauplii, 24 hours old nauplii, and 48 hours old nauplii which were collected from one cycle of production ...

  6. Dynamic Behaviors of Supersonic Granular Media under Vertical Vibration

    OpenAIRE

    Huang, Kai; Zhang, Peng; Miao, Guoqing; Wei, Rongjue

    2005-01-01

    We present experimental study of vibrofluidized granular materials by high speed photography. Statistical results present the averaged dynamic behaviors of granular materials in one cycle, including the variations of height, velocity and mechanical energy of the center of mass. Furthermore, time-space distribution of granular temperature which corresponds to the random kinetic energy shows that a temperature peak forms in the compression period and propagates upward with a steepened front. Th...

  7. Freeze-thaw and high-voltage discharge allow macromolecule uptake into ileal brush-border vesicles

    International Nuclear Information System (INIS)

    High-voltage discharge or one cycle of freeze-thawing are shown to transiently permeabilize rabbit ileal brush-border membrane vesicles to macromolecules. Uptake of the radiolabeled macromolecule dextran, mol wt 70,000, used as a marker for vesicle permeability, was determined by a rapid filtration technique, with uptake defined as substrate associated with the vesicle and releasable after incubation of vesicles with 0.1% saponin. Dextran added immediately after electric shock (2000 V) or at the beginning of one cycle of freeze-thawing was taken up approximately eightfold compared with control. ATP also was taken up into freeze-thawed vesicles, whereas there was no significant uptake into control vesicles. The increase in vesicle permeability was reversible, based on Na-dependent D-glucose uptake being decreased when studied 5 but not 15 min after electric shock, and was not significantly decreased after completion of one cycle of freeze-thawing. In addition, adenosine 3',5'-cyclic monophosphate and Ca2+-calmodulin-dependent protein kinase activity were similar in control vesicles and vesicles exposed to high-voltage discharge or freeze-thawing. Also, vesicles freeze-thawed with [32P]ATP demonstrated increased phosphorylation compared with nonfrozen vesicles, while freeze-thawing did not alter vesicle protein as judged by Coomassie blue staining. These techniques should allow intestinal membrane vesicles to be used for studies of intracellular control of transport processes, for instance, studies of protein kinase regulation of transport

  8. Verification of rod safety via confidence intervals for a binomial proportion

    International Nuclear Information System (INIS)

    The probabilistic safety assessed to a set of N fuel rods assembled in one core of a nuclear power reactor is commonly modelled by Σ i≤N X i, where X 1, ..., X N are independent Bernoulli random variables (rv) with individual probability p i = P (X i = 1) that the ith rod shows no failure during one cycle. This is the probability of the event that the ith rod will not exceed the failure limit during one cycle. The safety standard presently set by the German Reaktor-Sicherheitskommission (Reactor Safety Commission) requires that the expected number of unfailed rods in the core during one cycle is at least N - 1, i.e., E(Σ i≤N X i) = Σ i≤N p i ≥ N - 1, whereby a confidence level of 0.95 for the verification of this condition is demanded. In this paper, we provide an approach, based on the Clopper-Pearson confidence interval for the proportion p of a binomial B(n, p) distribution, how to verify this condition with a confidence level of at least 0.95. We extend our approach to the case, where the set of N fuel rods is arranged in strata, possibly due to different design in each stratum

  9. Freeze-thaw and high-voltage discharge allow macromolecule uptake into ileal brush-border vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Donowitz, M.; Emmer, E.; McCullen, J.; Reinlib, L.; Cohen, M.E.; Rood, R.P.; Madara, J.; Sharp, G.W.G.; Murer, H.; Malmstrom, K.

    1987-06-01

    High-voltage discharge or one cycle of freeze-thawing are shown to transiently permeabilize rabbit ileal brush-border membrane vesicles to macromolecules. Uptake of the radiolabeled macromolecule dextran, mol wt 70,000, used as a marker for vesicle permeability, was determined by a rapid filtration technique, with uptake defined as substrate associated with the vesicle and releasable after incubation of vesicles with 0.1% saponin. Dextran added immediately after electric shock (2000 V) or at the beginning of one cycle of freeze-thawing was taken up approximately eightfold compared with control. ATP also was taken up into freeze-thawed vesicles, whereas there was no significant uptake into control vesicles. The increase in vesicle permeability was reversible, based on Na-dependent D-glucose uptake being decreased when studied 5 but not 15 min after electric shock, and was not significantly decreased after completion of one cycle of freeze-thawing. In addition, adenosine 3',5'-cyclic monophosphate and Ca/sup 2 +/-calmodulin-dependent protein kinase activity were similar in control vesicles and vesicles exposed to high-voltage discharge or freeze-thawing. Also, vesicles freeze-thawed with (/sup 32/P)ATP demonstrated increased phosphorylation compared with nonfrozen vesicles, while freeze-thawing did not alter vesicle protein as judged by Coomassie blue staining. These techniques should allow intestinal membrane vesicles to be used for studies of intracellular control of transport processes, for instance, studies of protein kinase regulation of transport.

  10. Uniqueness of black holes with bubbles in minimal supergravity

    International Nuclear Information System (INIS)

    We generalize uniqueness theorems for non-extremal black holes with three mutually independent Killing vector fields in five-dimensional minimal supergravity in order to account for the existence of non-trivial two-cycles in the domain of outer communication. The black hole space-times we consider may contain multiple disconnected horizons and be asymptotically flat or asymptotically Kaluza–Klein. We show that in order to uniquely specify the black hole space-time, besides providing its domain structure and a set of asymptotic and local charges, it is necessary to measure the magnetic fluxes that support the two-cycles as well as fluxes in the two semi-infinite rotation planes of the domain diagram. (paper)

  11. Inverting geometric transitions: Explicit Calabi-Yau metrics for the Maldacena-Nunez solutions

    International Nuclear Information System (INIS)

    Explicit Calabi-Yau metrics are derived that are argued to map to the Maldacena-Nunez AdS solutions of M-theory and IIB under geometric transitions. In each case the metrics are singular where a H2 Kaehler two-cycle degenerates but are otherwise smooth. They are derived as the most general Calabi-Yau solutions of an ansatz for the supergravity description of branes wrapped on Kaehler two-cycles. The ansatz is inspired by rewriting the AdS solutions, and the structure defined by half their Killing spinors, in this form. The world-volume theories of fractional branes wrapped at the singularities of these metrics are proposed as the duals of the AdS solutions. The existence of supergravity solutions interpolating between the AdS and Calabi-Yau metrics is conjectured and their boundary conditions briefly discussed

  12. Improving The Organic Chemistry Teaching Learning Process And The Students' English Reading Comprehension

    OpenAIRE

    Srini M. Iskandar

    2016-01-01

    This study was aimed at the improvement of the Organic Chemistry II teaching learning process and the students' English reading comprehension. The design was a two cycled classroom action research whose activities are: in Cycle I the Learning Cycle was implemented using topics taken from an Indonesian Organic Chemistry textbook (Parlan, 2003), and also the Reciprocal Teaching Method using topics taken from an English[ Organic Chemistry textbook (Wade Jr, 1987). In Cycle II both models were im...

  13. The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

    International Nuclear Information System (INIS)

    We evaluated the role of 18F-FDG PET/CT for the assessment of response after two cycles of neo-adjuvant chemotherapy (NACT) for breast cancer. Twenty-three women with locally advanced breast cancer were included in this study. Early response to NACT was evaluated after two cycles using clinical examination, CT, and 18F-FDG PET/CT. Final histopathology following surgery after six cycles of NACT served as reference. Baseline PET/CT demonstrated a total of 26 lesions in 23 patients. The size of the primary tumor ranged from 1.90 cm to 11.60 cm, and the maximum value of the standardized uptake value of FDG (SUVmax) ranged from 3.6 to 38.6 (mean, 11.7). Post-chemotherapy PET/CT examinations were done after two cycles of NACT. The size of the primary tumor on follow-up PET/CT examinations ranged from 0.0 cm to 7.6 cm, and SUVmax ranged from 0.0 to 12.0 (mean, 3.96). On clinical, CT, and PET/CT examinations, 50% reduction in the parameters was taken as the cutoff value to differentiate between responders and non-responders. Post-NACT PET/CT demonstrated that 16 patients were responders and 7 non-responders. Among 16 responders on PET/CT scan, 14 were true positive and 2 were false positive when compared with histopathology. Among seven non-responder patients, six were true negative, and one was false negative. The sensitivity, specificity, and accuracy of PET/CT in detecting responders were 93%, 75%, and 87%, respectively. In conclusion, 18F-FDG PET/CT can differentiate responders from non-responders with high accuracy after two cycles of NACT in patients with LABC. (orig.)

  14. Response to induction chemotherapy as predictive marker of tumor response to radiotherapy and survival in oral cavity cancer

    OpenAIRE

    Surendra Kumar Saini; Shelly Srivastava; Shanbhu Nath Prasad

    2015-01-01

    Background: Trials have shown some statistically nonsignificant survival advantage of taxane, platin and 5-FU (TPF) induction chemotherapy before definitive chemoradiation. We tried to find the role of induction chemotherapy in the prediction of tumor response to radiotherapy and survival in the treatment of oral cavity cancers. Patients and Methods: Patients of stage III and IV (M0) unresectable oral cavity squamous cell carcinoma were assigned to receive two cycles of TPF. On the basis of r...

  15. Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma

    OpenAIRE

    Zhong, Lai-ping; Zhang, Chen-Ping; Ren, Guo-xin; Guo, Wei; William, William N.; Hong, Christopher S.; Sun, Jian; ZHU, HAN-GUANG; Tu, Wen-yong; Li, Jiang; Cai, Yi-li; Yin, Qiu-ming; WANG, LI-ZHEN; Wang, Zhong-he; Hu, Yong-jie

    2015-01-01

    Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75m...

  16. MENINGKATKAN HASIL BELAJAR PKN MELALUI MEDIA BERBASIS TIK PADA SISWA KELAS V SD FRATER DON BOSCO TARAKAN

    OpenAIRE

    Ursula Tuto Kemaun

    2011-01-01

    "Tuto Kemaun Ursula 2011, PKN Improve Learning Outcomes hrough ICT-Based Media in class V student of Don Bosco Brother SD Tarakan Year 2010/2011 lessons. Classroom Action Research goal is to improve student learning outcomes in particular grade 5B SD Frater Don Bosco Tarakan through the medium of ICT-based learning civic education so that learning becomes more enjoyable, challenging, and lead to creativity. Design research is done through two cycles, starting from planning, implementation mea...

  17. Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

    OpenAIRE

    Ahitagni Biswas; Pramod Kumar Julka

    2016-01-01

    Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13 year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the...

  18. Hitting Diamonds and Growing Cacti

    Science.gov (United States)

    Fiorini, Samuel; Joret, Gwenaël; Pietropaoli, Ugo

    We consider the following NP-hard problem: in a weighted graph, find a minimum cost set of vertices whose removal leaves a graph in which no two cycles share an edge. We obtain a constant-factor approximation algorithm, based on the primal-dual method. Moreover, we show that the integrality gap of the natural LP relaxation of the problem is Θ(logn), where n denotes the number of vertices in the graph.

  19. Management of premenstrual acne with Cox-2 inhibitors: A placebo controlled study

    OpenAIRE

    Tehrani Rustom; Dharmalingam Mala

    2004-01-01

    BACKGROUND: Premenstrual acne is poorly understood, the accepted hypothesis is 30 years old. AIMS: Here we test the hypothesis that premenstrual acne can be suppressed using Cox-2 inhibitors. METHODS: Eighty women with premenstrual acne were enrolled in a trial where they were given rofecoxib, a Cox-2 inhibitor or placebo for 10 days for two cycles and were evaluated using acne severity index and inflammatory acne counts. RESULTS: Rofecoxib was more effective than the placebo. CONCLUSIONS: Al...

  20. Leishmaniasis in the Tongue of an Immunocompetent Man

    OpenAIRE

    Leitner, Verena; Weingast, Jessika; Harmankaya, Kaan; Walochnik, Julia; Pehamberger, Hubert; Petzelbauer, Peter; Auer, Herbert; Binder, Michael

    2010-01-01

    A 49-year-old immunocompetent white man had a painful ulcer (1.5 cm in diameter) on the left ventrolateral surface of a grossly enlarged tongue. The ulcer was present for two months. Impaired swallowing resulted in substantial weight loss and fatigue. Histopathologic analysis of a punch biopsy specimen indicated numerous Leishman Donovan bodies within macrophages. A polymerase chain reaction confirmed the presence of L. donovani. Therapy with two cycles of liposomal amphotericin B over a thre...

  1. Clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital

    OpenAIRE

    Qureshi, Fawad; Shafi, Azhar; Ali, Sheeraz; Siddiqui, Neelam

    2016-01-01

    Objective: To determine the clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital. Methods: This was a cross-sectional study conducted on 200 patients undergoing first line chemotherapy with minimum of two cycles at inpatient department and chemotherapy bay of Shaukat Khanum Memorial Cancer Hospital and Research Centre Pakistan. Anticipatory nausea and vomiting develops before administration of chemotherapy. Clinical signs and symp...

  2. Identification of the difficulties in teaching and learning of introductory organic chemistry in Ireland and the development of a second-level intervention programme to address these

    OpenAIRE

    O'Dwyer, Anne

    2012-01-01

    peer-reviewed This project involved the effective implementation of Chemistry Education Research (CER) into classroom practice. The project was carried out in two cycles. Cycle One of the project involved two investigations: one at second-level and one at third-level. Cycle Two involved the development, implementation and evaluation of an intervention in the Irish second-level schools programme to address the issues identified in Cycle One. The difficulties of organic chemis...

  3. Centrifuge modeling of soil atmosphere interaction using climatic chamber

    OpenAIRE

    CAICEDO, B; TRISTANCHO, J; THOREL, Luc

    2010-01-01

    Soil-atmospheric interaction processes such as infiltration or evaporation can have a significant effect on the behavior of geotechnical structures located near the soil surface. This paper focuses on the drying process of soils due to evaporation. The scaling laws are analyzed and the results of the application of two cycles of heating and cooling on a soil mass are presented. Based on these results, conclusions about the feasibility of reproducing evaporation on centrifuge models are recomm...

  4. Centrifuge modeling of soil atmosphere interaction

    OpenAIRE

    CAICEDO, B; TRISTANCHO, J; THOREL, Luc

    2010-01-01

    Atmosphere process of infiltration or evaporation affect the behavior of geotechnical structures located near the soil surface. This paper focuses on the drying process of soils due to evaporation. The scaling laws are analyzed and afterwards the results on applying two cycles of heating and cooling on a soil mass are presented. Based on these results, conclusions about the feasibility of reproducing evaporation on centrifuge models are recommended.

  5. The effects of laser assisted hatching on pregnancy rates

    OpenAIRE

    Alireza Ghannadi; Marjaneh Kazerooni; Fatemeh Jamalzadeh; Sahar Amiri; Parifar Rostami; Forouzan Absalan

    2011-01-01

    Background: For infertile women aged over 35 years, failure of the ZP (zona pellucida) to rupture is believed to be associated with a decreased implantation rate in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI). Objective: In this research, laser assisted hatching (LAH) was offered to patients with advanced maternal age to evaluate a possible benefit. Materials and Methods: Nine hundred thirty two cycles of IVF/ICSI in females were analyzed. Women included in this s...

  6. Business Tourism Aspects of Film Tourism: The Case of Budapest

    OpenAIRE

    Anna Irimias

    2015-01-01

    One of the possible ways to enhance Europe visibility, its entirety rather than a set of destinations, is implementing cooperation between the Member States especially in creating and developing trans-border thematic tourist products and experiences. One of them could be the film-induced tourism. In looking back over the past two cycles of European programming it is possible to find some examples, described in the article, in which the theme of audiovisual productions in their shooting phase ...

  7. Film-induced, steps for a Real Exploitation in Europe

    OpenAIRE

    Francesco di Cesare; Anthony La Salandra

    2015-01-01

    One of the possible ways to enhance Europe visibility, its entirety rather than a set of destinations, is implementing cooperation between the Member States especially in creating and developing trans-border thematic tourist products and experiences. One of them could be the film-induced tourism. In looking back over the past two cycles of European programming it is possible to find some examples, described in the article, in which the theme of audiovisual productions in their shooting phase ...

  8. Estratigrafía y sedimentología del Muschelkalk inferior del dominio Monrserrat-Llobregat (Catalanides)

    OpenAIRE

    Calvet, F.; Ramon, X.

    1987-01-01

    The sedimentary evolution of the lower Muschelkalk (facies) in the Catalan Coastal range is characterized by the existence of two cycles: deepening and shallowing upwards. A regional discontinuity exists between these two main cycles. However shallowing upwards sequences occur throughout all the carbonate section studied. Secondary dolomitization took place in the upper part of the lower (deepening) sequence enhanced by the existing regional discontinuity. Primary dolomite occurs in the sha...

  9. UJI COBA PENYEMPROTAN ULV (ULV SPRAYING INSEKTISIDA BENDIOCARB 20 % (FICAM ULV TERHADAP VEKTOR DEMAM BERDARAH DENGUE Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Hadi Suwasono

    2012-09-01

    Full Text Available A trial was conducted using ULV spraying of Bendiocarb 20% (Ficam ULV in Salatiga municipality at a dosage of 45 ml/ha and 75 ml/ha. The trial was conducted in the morning. Two cycles were implemented at an interval of 7 days, using a vehicle-mounted ULV generator. Results revealed no significant changes in mosquito population densitities, in any of the parameters observed.

  10. Socioeconomic gradient in consumption of whole fruit and 100% fruit juice among US children and adults

    OpenAIRE

    Drewnowski, Adam; Rehm, Colin D.

    2015-01-01

    Background The consumption of fruit is generally associated with better health, but also higher socioeconomic status (SES). Most previous studies evaluating consumption of fruits have not separated 100% fruit juice and whole fruit, which may conceal interesting patterns in consumption. Objective To estimate demographic and socioeconomic correlates of whole fruit versus 100% juice consumption among children and adults in the United States. Design Secondary analyses of two cycles of the nationa...

  11. Effect of decoherence on the Berry phase of a spin-half in a rotating magnetic field

    OpenAIRE

    LI, XIN; Shi, Yu

    2013-01-01

    We investigate the decoherence effect of a bosonic bath on the Berry phase of a spin-1/2 in a time-dependent magnetic field, without making the Markovian approximation. A two-cycle process resulting in a pure Berry phase is considered. The low-frequency quantum noise significantly affects the Berry phase. In the adiabatic limit, the high-frequency quantum noise only has a small effect. The result is also valid in some more general situations.

  12. Subquivers of mutation-acyclic quivers are mutation-acyclic

    CERN Document Server

    Warkentin, Matthias

    2011-01-01

    Quiver mutation plays a crucial role in the definition of cluster algebras by Fomin and Zelevinsky. It induces an equivalence relation on the set of all quivers without loops and two-cycles. A quiver is called mutation-acyclic if it is mutation-equivalent to an acyclic quiver. The aim of this note is to show that full subquivers of mutation-acyclic quivers are mutation-acyclic.

  13. Autologous Platelet Gel: An In Vitro Analysis of Platelet-Rich Plasma Using Multiple Cycles

    OpenAIRE

    Christensen, Kevin; Vang, See; Brady, Chad; Isler, Jack; Allen, Keith; Anderson, John; Holt, David

    2006-01-01

    Autologous platelet gel (APG) has become an expanding field for perfusionists. By mixing platelet-rich plasma (PRP) with thrombin and calcium, platelet gel is prepared and used in many surgical settings. There are many devices used to produce PRP. This study evaluates the Medtronic Magellan Autologous Platelet Separator. The purpose of this study was to show that processing two cycles of the same syringe could reduce the amount of blood required to produce a specific volume of PRP. Three 60-m...

  14. Fault Line Selection Method of Small Current to Ground System Based on Atomic Sparse Decomposition and Extreme Learning Machine

    OpenAIRE

    Xiaowei Wang; Yanfang Wei; Zhihui Zeng; Yaxiao Hou; Jie Gao; Xiangxiang Wei

    2015-01-01

    This paper proposed a fault line voting selection method based on atomic sparse decomposition (ASD) and extreme learning machine (ELM). Firstly, it adopted ASD algorithm to decompose zero sequence current of every feeder line at first two cycles and selected the first four atoms to construct main component atom library, fundamental atom library, and transient characteristic atom libraries 1 and 2, respectively. And it used information entropy theory to calculate the atom libraries; the measur...

  15. PENGGUNAAN MULTIMEDIA INTERAKTIF BERBASI

    OpenAIRE

    Utami, Sri; Mayasari, Tantri; Handika, Jefri

    2015-01-01

    This research is served to develop teaching instruments which refer to 4-D Model, including: interactive multimedia, Lesson Plan, Syllabus, Student Worksheet and Evaluation, for the subject of Genetics through two-cycle action research. This research aso attempts to develop the effectiveness of teaching by the application of teaching media which visualize the abstract concepts of the Genetics class consisting of 42 students of semester IV class D of Biology Study Program, the Faculty of Natur...

  16. Positivity of heights of codimension 2 cycles over function field of characteristic 0

    CERN Document Server

    Zhang, Shou-Wu

    2010-01-01

    In this note, we show how the classical Hodge index theorem implies the Hodge index conjecture of Beilinson for height pairing of homologically trivial codimension two cycles over function field of characteristic 0. Such an index conjecture has been used in our paper on Gross-Schoen cycles to deduce the Bogomolov conjecture and a lower bound for Hodge class (or Faltings height) from some conjectures about metrized graphs which have just been recently proved by Zubeyir Cinkir.

  17. Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency

    OpenAIRE

    Fan, Dongsheng; Soei, Lou Kie; Sassen, L. M.; Krams, Rob; Verdouw, Pieter

    1994-01-01

    textabstractOxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data. Methods: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary...

  18. Clinical value of hematologic test in predicting tumor response to neoadjuvant chemotherapy with esophageal squamous cell carcinoma

    OpenAIRE

    Liu, Yinan; Chen, Jinfeng; Shao, Ningsheng; Feng, Yuan; Wang, Yuzhao; Zhang, Lijian

    2014-01-01

    Background To investigate the relationship between hematologic test results and the predictive effect of regression of esophageal cancer after neoadjuvant chemotherapy (NACT), we analyzed pre-NACT hematologic data and their relationship to tumor regression. Methods Thirty-eight consecutive patients with locally advanced squamous cell esophageal carcinoma who had undergone two cycles of paclitaxel/carboplatin NACT were enrolled. On the day prior to the first cycle of chemotherapy, hematologic ...

  19. The role of {sup 18}F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Amandeep; Seenu, Vathalaru; Mehta, Sada Nand [All India Institute of Medical Sciences, Department of Surgical disciplines, New Delhi (India); Kumar, Rakesh; Chawla, Madhavi; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Gupta, Sidharatha Datta [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India)

    2009-06-15

    We evaluated the role of 18F-FDG PET/CT for the assessment of response after two cycles of neo-adjuvant chemotherapy (NACT) for breast cancer. Twenty-three women with locally advanced breast cancer were included in this study. Early response to NACT was evaluated after two cycles using clinical examination, CT, and 18F-FDG PET/CT. Final histopathology following surgery after six cycles of NACT served as reference. Baseline PET/CT demonstrated a total of 26 lesions in 23 patients. The size of the primary tumor ranged from 1.90 cm to 11.60 cm, and the maximum value of the standardized uptake value of FDG (SUVmax) ranged from 3.6 to 38.6 (mean, 11.7). Post-chemotherapy PET/CT examinations were done after two cycles of NACT. The size of the primary tumor on follow-up PET/CT examinations ranged from 0.0 cm to 7.6 cm, and SUVmax ranged from 0.0 to 12.0 (mean, 3.96). On clinical, CT, and PET/CT examinations, 50% reduction in the parameters was taken as the cutoff value to differentiate between responders and non-responders. Post-NACT PET/CT demonstrated that 16 patients were responders and 7 non-responders. Among 16 responders on PET/CT scan, 14 were true positive and 2 were false positive when compared with histopathology. Among seven non-responder patients, six were true negative, and one was false negative. The sensitivity, specificity, and accuracy of PET/CT in detecting responders were 93%, 75%, and 87%, respectively. In conclusion, 18F-FDG PET/CT can differentiate responders from non-responders with high accuracy after two cycles of NACT in patients with LABC. (orig.)

  20. MENINGKATKAN HASIL BELAJAR SEJARAH SISWA MELALUI PENDEKATAN PEMBELAJARAN KONTEKSTUAL DENGAN MEDIA VCD PEMBELAJARAN

    OpenAIRE

    Atno Atno

    2011-01-01

    The purpose of this study was to improve learning outcomes of students with the application of contextual learning using VCD learning media in the subject of history, in grade XI IPA 1 SMA N 1 Banjarnegara, in the academic year of 2009/2010. The study used class action research approach with stages consisting of two cycles. Research data obtained by using interviews and observation with the observation sheet and evaluation tests. Data analysis technique used in this study is simple descriptiv...

  1. Embedding library in study structure

    OpenAIRE

    Heino, Kirsi; Palmgren, Virpi

    2006-01-01

    In Europe, the Bologna process aims at the harmonisation of the structure of higher education in order to facilitate mobility. In the context of engineering education, the trans-national recognition of engineering degrees, academically and professionally, is a primary goal. In Finland, the two-cycle degree structure to be adopted in the Bologna process will introduce the Bachelor's degree to supplement the Master's degree in university engineering education. At TKK, Helsinki University of Tec...

  2. Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hawthorn Lesleyann

    2010-08-01

    Full Text Available Abstract Background A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs. This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'. Methods We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs. Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH analysis to identify genes showing altered expression in LOH regions. Results Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples. Conclusion We have demonstrated the utility of the application of

  3. EMAAS: An extensible grid-based Rich Internet Application for microarray data analysis and management

    Directory of Open Access Journals (Sweden)

    Aitman T

    2008-11-01

    Full Text Available Abstract Background Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management. Results EMAAS (Extensible MicroArray Analysis System is a multi-user rich internet application (RIA providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms. Conclusion EMAAS enables users to track and perform microarray data

  4. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

    Directory of Open Access Journals (Sweden)

    Garcia Juan L

    2010-08-01

    Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

  5. Validation and characterization of DNA microarray gene expression data distribution and associated moments

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    Chang Xiaoqing

    2010-11-01

    Full Text Available Abstract Background The data from DNA microarrays are increasingly being used in order to understand effects of different conditions, exposures or diseases on the modulation of the expression of various genes in a biological system. This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking. Results Best fit hypotheses tests, moment-ratio diagrams and relationships between the different moments of the distribution of the gene expression was used to characterize the observed distributions. The data are obtained from the publicly available gene expression database, Gene Expression Omnibus (GEO to characterize the empirical distributions of gene expressions obtained under varying experimental situations each of which providing relatively large number of samples for hypothesis testing. All data were obtained from either of two microarray platforms - the commercial Affymetrix mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each platform were preprocessed in the same manner. Conclusions The null hypotheses for goodness of fit for all considered univariate theoretical probability distributions (including the Normal distribution are rejected for more than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesting that under the tested conditions a priori assumption of any of these distributions across all probe sets is not valid. The pattern of null hypotheses rejection was different for the data from Rosetta/Merck platform with only around 20% of the probe sets failing the logistic distribution goodness-of-fit test. We find that there are statistically significant (at 95% confidence level based on the F

  6. Gene expression profiling reveals different pathways related to Abl and other genes that cooperate with c-Myc in a model of plasma cell neoplasia

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    Zhan Fenghuang

    2007-08-01

    Full Text Available Abstract Background To elucidate the genes involved in the neoplastic transformation of B cells, global gene expression profiles were generated using Affymetrix U74Av2 microarrays, containing 12,488 genes, for four different groups of mouse B-cell lymphomas and six subtypes of pristane-induced mouse plasma cell tumors, three of which developed much earlier than the others. Results Unsupervised hierarchical cluster analysis exhibited two main sub-clusters of samples: a B-cell lymphoma cluster and a plasma cell tumor cluster with subclusters reflecting mechanism of induction. This report represents the first step in using global gene expression to investigate molecular signatures related to the role of cooperating oncogenes in a model of Myc-induced carcinogenesis. Within a single subgroup, e.g., ABPCs, plasma cell tumors that contained typical T(12;15 chromosomal translocations did not display gene expression patterns distinct from those with variant T(6;15 translocations, in which the breakpoint was in the Pvt-1 locus, 230 kb 3' of c-Myc, suggesting that c-Myc activation was the initiating factor in both. When integrated with previously published Affymetrix array data from human multiple myelomas, the IL-6-transgenic subset of mouse plasma cell tumors clustered more closely with MM1 subsets of human myelomas, slow-appearing plasma cell tumors clustered together with MM2, while plasma cell tumors accelerated by v-Abl clustered with the more aggressive MM3-MM4 myeloma subsets. Slow-appearing plasma cell tumors expressed Socs1 and Socs2 but v-Abl-accelerated plasma cell tumors expressed 4–5 times as much. Both v-Abl-accelerated and non-v-Abl-associated tumors exhibited phosphorylated STAT 1 and 3, but only v-Abl-accelerated plasma cell tumors lost viability and STAT 1 and 3 phosphorylation when cultured in the presence of the v-Abl kinase inhibitor, STI-571. These data suggest that the Jak/Stat pathway was critical in the transformation

  7. Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis

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    Aigner Ludwig

    2008-05-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE induced by myelin oligodendrocyte protein (MOG in female Dark Agouti (DA rats is a chronic demyelinating animal model of multiple sclerosis (MS. To identify new candidate molecules involved in the evolution or repair of EAE-lesions we used Affymetrix oligonucleotide microarrays to compare the spinal cord transcriptome at the peak of EAE, during remission and at the first relapse with healthy DA rats. Methods Untreated DA rats and DA rats immunised with MOG protein were sacrificed at defined time points. Total RNA was isolated from spinal cord tissue and used for hybridization of Affymetrix rat genome arrays RG U34 A-C. Selected expression values were confirmed by RealTime PCR. Adult neural stem cells were incubated with recombinant secretory leukocyte protease inhibitor (SLPI. Proliferation was assessed by BrdU incorporation, cyclin D1 and HES1 expression by RealTime PCR, cell differentiation by immunofluorescence analysis and IkappaBalpha degradation by Western blot. Results Among approximately 26,000 transcripts studied more than 1,100 were differentially regulated. Focussing on functional themes, we noticed a sustained downregulation of most of the transcripts of the cholesterol biosynthesis pathway. Furthermore, we found new candidate genes possibly contributing to regenerative processes in the spinal cord. Twelve transcripts were solely upregulated in the recovery phase, including genes not previously associated with repair processes. Expression of SLPI was upregulated more than hundredfold during EAE attack. Using immunohistochemistry, SLPI was identified in macrophages, activated microglia, neuronal cells and astrocytes. Incubation of adult neural stem cells (NSC with recombinant SLPI resulted in an increase of cell proliferation and of differentiation towards oligodendrocytes. These processes were paralleled by an upregulation of the cell-cycle promotor cyclin D1 and a

  8. High-resolution analysis of DNA copy number alterations in rectal cancer. Correlation with metastasis, survival, and mRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, Jerome; Gerard, Jean-Pierre [Centre Antoine-Lacassagne, Department of Radiation Oncology, Nice (France); University of Nice Sophia-Antipolis, Nice (France); Letouze, Eric; Marisa, Laetitia; Reynies, Aurelien de [Ligue Nationale Contre Le Cancer, Programme Cartes d' Identite des Tumeurs, Paris (France); Milano, Gerard; Etienne-Grimaldi, Marie-Christine [University of Nice Sophia-Antipolis, Nice (France); Centre Antoine-Lacassagne, Oncopharmacology Unit, Nice (France); Olschwang, Sylviane [INSERM U1068, Marseille (France); Gaedcke, Jochen; Ghadimi, Michael [University Medical Center Goettingen, Department of General and Visceral Surgery, Goettingen (Germany)

    2014-11-15

    This study aimed to determine the candidate genes and chromosomal imbalances capable of predicting occurrences of metastasis in patients with rectal cancer. Fresh frozen tumor tissues from 80 patients with rectal cancer were prospectively collected and analyzed using Affymetrix HG-U133 Plus 2.0 gene expression arrays and high-resolution Illumina single-nucleotide polymorphism (SNP) arrays. Endpoints of the study were metastasis-free survival (MFS) and cancer-specific survival (CSS). The median follow-up was 102 months (1-146). Deletions of 8p and 1p36-35 correlated with worse MFS (p = 0.005 and p = 0.01, respectively) and CSS (p = 0.001 and p = 0.01, respectively). Multivariate analysis identified 8p deletion as an independent prognostic factor for MFS (p = 0.04) and CSS (p = 0.003); 97 genes located on the 8p chromosome were significantly underexpressed in tumors with 8p deletion. This study shows for the first time in rectal cancer an independent correlation of 8p deletion with MFS and CSS and highlights potential new tumor suppressor genes. (orig.) [German] Diese Studie zielt darauf ab, Kandidatengene und chromosomale Ungleichgewichte vorherzusagen und das Auftreten von Metastasen bei Rektumkarzinompatienten zu bestimmen. Frisch gefrorenes Tumorgewebe von 80 Patienten mit Rektumkarzinom wurde prospektiv erfasst und mit Affymetrix-(HG-U133-Plus-2.0)-Genexpressionsarrays und hochaufloesenden Illumina-Single-Nukleotid-Polymorphismus-(SNP-)Arrays analysiert. Endpunkte der Studie waren fernmetastasenfreies Ueberleben (MFU) und krebsspezifisches Ueberleben (KSU). Die mediane Nachbeobachtungszeit betrug 102 Monate (1-146 Monate). Die Deletionen von 8p und 1p36-35 waren mit schlechterem MFU (jeweils p = 0,005 und p = 0,01) und KSU (jeweils p = 0,001 und p = 0,01) korreliert. Die multivariate Analyse identifizierte - 8p als unabhaengigen prognostischen Faktor fuer MFU (p = 0,04) und KSU (p = 0,003). In Tumoren mit einer 8p-Deletion waren 97 Gene auf Chromosom 8p

  9. DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids

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    Shou Jianyong

    2007-04-01

    Full Text Available Abstract Background Uterine fibroids or leiomyoma are a common benign smooth muscle tumor. The tumor growth is well known to be estrogen-dependent. However, the molecular mechanisms of its estrogen-dependency is not well understood. Methods Differentially expressed genes in human uterine fibroids were either retrieved from published papers or from our own statistical analysis of downloaded array data. Probes for the same genes on different Affymetrix chips were mapped based on probe comparison information provided by Affymetrix. Genes identified by two or three array studies were submitted for ortholog analysis. Human and rat ortholog genes were identified by using ortholog gene databases, HomoloGene and TOGA and were confirmed by synteny analysis with MultiContigView tool in the Ensembl genome browser. Results By integrated analysis of three recently published DNA microarray studies with human tissue, thirty-eight genes were found to be differentially expressed in the same direction in fibroid compared to adjacent uterine myometrium by at least two research groups. Among these genes, twelve with rat orthologs were identified as estrogen-regulated from our array study investigating uterine expression in ovariectomized rats treated with estrogen. Functional and pathway analyses of the twelve genes suggested multiple molecular mechanisms for estrogen-dependent cell survival and tumor growth. Firstly, estrogen increased expression of the anti-apoptotic PCP4 gene and suppressed the expression of growth inhibitory receptors PTGER3 and TGFBR2. Secondly, estrogen may antagonize PPARγ signaling, thought to inhibit fibroid growth and survival, at two points in the PPAR pathway: 1 through increased ANXA1 gene expression which can inhibit phospholipase A2 activity and in turn decrease arachidonic acid synthesis, and 2 by decreasing L-PGDS expression which would reduce synthesis of PGJ2, an endogenous ligand for PPARγ. Lastly, estrogen affects retinoic

  10. Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms (SNPs) Associated With the Development of Erectile Dysfunction in African-American Men After Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African-American prostate cancer patients treated with external beam radiation therapy. Methods and Materials: A cohort of African-American prostate cancer patients treated with external beam radiation therapy was observed for the development of ED by use of the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score ≤7) and 52 control subjects (post-treatment SHIM score ≥16). A genome-wide association study was performed using approximately 909,000 SNPs genotyped on Affymetrix 6.0 arrays (Affymetrix, Santa Clara, CA). Results: We identified SNP rs2268363, located in the follicle-stimulating hormone receptor (FSHR) gene, as significantly associated with ED after correcting for multiple comparisons (unadjusted p = 5.46 x 10-8, Bonferroni p = 0.028). We identified four additional SNPs that tended toward a significant association with an unadjusted p value -6. Inference of population substructure showed that cases had a higher proportion of African ancestry than control subjects (77% vs. 60%, p = 0.005). A multivariate logistic regression model that incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate classifier of ED than a model that included only clinical variables. Conclusions: To our knowledge, this is the first genome-wide association study to identify SNPs associated with adverse effects resulting from radiotherapy. It is important to note that the SNP that proved to be significantly associated with ED is located within a gene whose encoded product plays a role in male gonad development and function. Another key finding of this project is that the four SNPs most strongly associated with ED were specific to persons of African ancestry and would therefore not have been identified had a cohort of European ancestry been screened. This study demonstrates the

  11. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

    International Nuclear Information System (INIS)

    Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location

  12. Evaluating gene expression in C57BL/6J and DBA/2J mouse striatum using RNA-Seq and microarrays.

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    Daniel Bottomly

    Full Text Available C57BL/6J (B6 and DBA/2J (D2 are two of the most commonly used inbred mouse strains in neuroscience research. However, the only currently available mouse genome is based entirely on the B6 strain sequence. Subsequently, oligonucleotide microarray probes are based solely on this B6 reference sequence, making their application for gene expression profiling comparisons across mouse strains dubious due to their allelic sequence differences, including single nucleotide polymorphisms (SNPs. The emergence of next-generation sequencing (NGS and the RNA-Seq application provides a clear alternative to oligonucleotide arrays for detecting differential gene expression without the problems inherent to hybridization-based technologies. Using RNA-Seq, an average of 22 million short sequencing reads were generated per sample for 21 samples (10 B6 and 11 D2, and these reads were aligned to the mouse reference genome, allowing 16,183 Ensembl genes to be queried in striatum for both strains. To determine differential expression, 'digital mRNA counting' is applied based on reads that map to exons. The current study compares RNA-Seq (Illumina GA IIx with two microarray platforms (Illumina MouseRef-8 v2.0 and Affymetrix MOE 430 2.0 to detect differential striatal gene expression between the B6 and D2 inbred mouse strains. We show that by using stringent data processing requirements differential expression as determined by RNA-Seq is concordant with both the Affymetrix and Illumina platforms in more instances than it is concordant with only a single platform, and that instances of discordance with respect to direction of fold change were rare. Finally, we show that additional information is gained from RNA-Seq compared to hybridization-based techniques as RNA-Seq detects more genes than either microarray platform. The majority of genes differentially expressed in RNA-Seq were only detected as present in RNA-Seq, which is important for studies with smaller effect sizes

  13. Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

    International Nuclear Information System (INIS)

    Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines. Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest. Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known JUNB, FOS and TP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as SERPINE1 and MMP7, are known to regulate metastasis. Twenty-one genes including VEGFA and ID2 have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis. The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in

  14. Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity

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    Gallagher Iain J

    2011-03-01

    Full Text Available Abstract Background Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components of the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Methods Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation to yield global profiles of miRNAs. Results We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided. Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p Conclusion In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of

  15. Inter-Platform comparability of microarrays in acute lymphoblastic leukemia

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    Mintz Michelle

    2004-09-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS rates improving from 80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21[TEL-AML1], t(4;11[MLL-AF4], t(9;22[BCR-ABL], and t(1;19[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. Results We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors

  16. Medicago truncatula and Glomus intraradices gene expression in cortical cells harboring arbuscules in the arbuscular mycorrhizal symbiosis

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    Tang Yuhong

    2009-01-01

    Full Text Available Abstract Background Most vascular flowering plants have the capacity to form symbiotic associations with arbuscular mycorrhizal (AM fungi. The symbiosis develops in the roots where AM fungi colonize the root cortex and form arbuscules within the cortical cells. Arbuscules are enveloped in a novel plant membrane and their establishment requires the coordinated cellular activities of both symbiotic partners. The arbuscule-cortical cell interface is the primary functional interface of the symbiosis and is of central importance in nutrient exchange. To determine the molecular events the underlie arbuscule development and function, it is first necessary to identify genes that may play a role in this process. Toward this goal we used the Affymetrix GeneChip® Medicago Genome Array to document the M. truncatula transcript profiles associated with AM symbiosis, and then developed laser microdissection (LM of M. truncatula root cortical cells to enable analyses of gene expression in individual cell types by RT-PCR. Results This approach led to the identification of novel M. truncatula and G. intraradices genes expressed in colonized cortical cells and in arbuscules. Within the arbuscule, expression of genes associated with the urea cycle, amino acid biosynthesis and cellular autophagy was detected. Analysis of gene expression in the colonized cortical cell revealed up-regulation of a lysine motif (LysM-receptor like kinase, members of the GRAS transcription factor family and a symbiosis-specific ammonium transporter that is a likely candidate for mediating ammonium transport in the AM symbiosis. Conclusion Transcript profiling using the Affymetrix GeneChip® Medicago Genome Array provided new insights into gene expression in M. truncatula roots during AM symbiosis and revealed the existence of several G. intraradices genes on the M. truncatula GeneChip®. A laser microdissection protocol that incorporates low-melting temperature Steedman's wax, was

  17. A Thermodynamic Analysis of Two Competing Mid-Sized Oxyfuel Combustion Combined Cycles

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    Egill Thorbergsson

    2016-01-01

    Full Text Available A comparative analysis of two mid-sized oxyfuel combustion combined cycles is performed. The two cycles are the semiclosed oxyfuel combustion combined cycle (SCOC-CC and the Graz cycle. In addition, a reference cycle was established as the basis for the analysis of the oxyfuel combustion cycles. A parametric study was conducted where the pressure ratio and the turbine entry temperature were varied. The layout and the design of the SCOC-CC are considerably simpler than the Graz cycle while it achieves the same net efficiency as the Graz cycle. The fact that the efficiencies for the two cycles are close to identical differs from previously reported work. Earlier studies have reported around a 3% points advantage in efficiency for the Graz cycle, which is attributed to the use of a second bottoming cycle. This additional feature is omitted to make the two cycles more comparable in terms of complexity. The Graz cycle has substantially lower pressure ratio at the optimum efficiency and has much higher power density for the gas turbine than both the reference cycle and the SCOC-CC.

  18. Identification of novel Notch target genes in T cell leukaemia

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    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  19. RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism.

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    Soueid, Jihane; Kourtian, Silva; Makhoul, Nadine J; Makoukji, Joelle; Haddad, Sariah; Ghanem, Simona S; Kobeissy, Firas; Boustany, Rose-Mary

    2016-01-01

    Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal and non-verbal communication. Objectives were to determine the contribution of genetic variation to ASDs in the Lebanese. Affymetrix Cytogenetics Whole-Genome 2.7 M and CytoScan(™) HD Arrays were used to detect CNVs in 41 Lebanese autistic children and 35 non-autistic, developmentally delayed and intellectually disabled patients. 33 normal participants were used as controls. 16 de novo CNVs and 57 inherited CNVs, including recognized pathogenic 16p11.2 duplications and 2p16.3 deletions were identified. A duplication at 1q43 classified as likely pathogenic encompasses RYR2 as a potential ASD candidate gene. This previously identified CNV has been classified as both pathogenic, and, of uncertain significance. A duplication of unknown significance at 10q11.22, proposed as a modulator for phenotypic disease expression in Rett syndrome, was also identified. The novel potential autism susceptibility genes PTDSS1 and AREG were uncovered and warrant further genetic and functional analyses. Previously described and novel genetic targets in ASD were identified in Lebanese families with autism. These findings may lead to improved diagnosis of ASDs and informed genetic counseling, and may also lead to untapped therapeutic targets applicable to Lebanese and non-Lebanese patients. PMID:26742492

  20. Pep1, a secreted effector protein of Ustilago maydis, is required for successful invasion of plant cells.

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    Gunther Doehlemann

    2009-02-01

    Full Text Available The basidiomycete Ustilago maydis causes smut disease in maize. Colonization of the host plant is initiated by direct penetration of cuticle and cell wall of maize epidermis cells. The invading hyphae are surrounded by the plant plasma membrane and proliferate within the plant tissue. We identified a novel secreted protein, termed Pep1, that is essential for penetration. Disruption mutants of pep1 are not affected in saprophytic growth and develop normal infection structures. However, Deltapep1 mutants arrest during penetration of the epidermal cell and elicit a strong plant defense response. Using Affymetrix maize arrays, we identified 116 plant genes which are differentially regulated in Deltapep1 compared to wild type infections. Most of these genes are related to plant defense. By in vivo immunolocalization, live-cell imaging and plasmolysis approaches, we detected Pep1 in the apoplastic space as well as its accumulation at sites of cell-to-cell passages. Site-directed mutagenesis identified two of the four cysteine residues in Pep1 as essential for function, suggesting that the formation of disulfide bridges is crucial for proper protein folding. The barley covered smut fungus Ustilago hordei contains an ortholog of pep1 which is needed for penetration of barley and which is able to complement the U. maydis Deltapep1 mutant. Based on these results, we conclude that Pep1 has a conserved function essential for establishing compatibility that is not restricted to the U. maydis / maize interaction.

  1. Analysis of Gene expression in soybean (Glycine max roots in response to the root knot nematode Meloidogyne incognita using microarrays and KEGG pathways

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    Gamal El-Din Abd El Kader Y

    2011-05-01

    Full Text Available Abstract Background Root-knot nematodes are sedentary endoparasites that can infect more than 3000 plant species. Root-knot nematodes cause an estimated $100 billion annual loss worldwide. For successful establishment of the root-knot nematode in its host plant, it causes dramatic morphological and physiological changes in plant cells. The expression of some plant genes is altered by the nematode as it establishes its feeding site. Results We examined the expression of soybean (Glycine max genes in galls formed in roots by the root-knot nematode, Meloidogyne incognita, 12 days and 10 weeks after infection to understand the effects of infection of roots by M. incognita. Gene expression was monitored using the Affymetrix Soybean GeneChip containing 37,500 G. max probe sets. Gene expression patterns were integrated with biochemical pathways from the Kyoto Encyclopedia of Genes and Genomes using PAICE software. Genes encoding enzymes involved in carbohydrate and cell wall metabolism, cell cycle control and plant defense were altered. Conclusions A number of different soybean genes were identified that were differentially expressed which provided insights into the interaction between M. incognita and soybean and into the formation and maintenance of giant cells. Some of these genes may be candidates for broadening plants resistance to root-knot nematode through over-expression or silencing and require further examination.

  2. Rice Transcriptome Analysis to Identify Possible Herbicide Quinclorac Detoxification Genes

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    Wenying eXu

    2015-09-01

    Full Text Available Quinclorac is a highly selective auxin-type herbicide, and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world’s rice yield. The herbicide mode of action of quinclorac has been proposed and hormone interactions affect quinclorac signaling. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and environmental health problems.In this study, we used 57K Affymetrix rice whole-genome array to identify quinclorac signaling response genes to study the molecular mechanisms of action and detoxification of quinclorac in rice plants. Overall, 637 probe sets were identified with differential expression levels under either 6 or 24 h of quinclorac treatment. Auxin-related genes such as GH3 and OsIAAs responded to quinclorac treatment. Gene Ontology analysis showed that genes of detoxification-related family genes were significantly enriched, including cytochrome P450, GST, UGT, and ABC and drug transporter genes. Moreover, real-time RT-PCR analysis showed that top candidate P450 families such as CYP81, CYP709C and CYP72A genes were universally induced by different herbicides. Some Arabidopsis genes for the same P450 family were up-regulated under quinclorac treatment.We conduct rice whole-genome GeneChip analysis and the first global identification of quinclorac response genes. This work may provide potential markers for detoxification of quinclorac and biomonitors of environmental chemical pollution.

  3. Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.

    Science.gov (United States)

    Shan, Ying; Zhang, Yikai; Zhuo, Xunhui; Li, Xiaoliang; Peng, Jinrong; Fang, Weihuan

    2016-07-01

    Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish. PMID:27068748

  4. A Microarray Based Genomic Hybridization Method for Identification of New Genes in Plants: Case Analyses of Arabidopsis and Oryza

    Institute of Scientific and Technical Information of China (English)

    Chuanzhu Fan; Maria D. Vibranovski; Ying Chen; Manyuan Long

    2007-01-01

    To systematically estimate the gene duplication events in closely related species, we have to use comparative genomic approaches, either through genomic sequence comparison or comparative genomic hybridization (CGH). Given the scarcity of complete genomic sequences of plant species, in the present study we adopted an array based CGH to investigate gene duplications in the genus Arabidopsis. Fragment genomic DNA from four species, namely Arabidopsis thaliana, A. lyrata subsp. lyrata, A. lyrata subsp. petraea, and A. halleri, was hybridized to Affymetrix (Santa Clara, CA, USA) tiling arrays that are designed from the genomic sequences of A. thaliana. Pairwise comparisons of signal intensity were made to infer the potential duplicated candidates along each phylo-genetic branch. Ninety-four potential candidates of gene duplication along the genus were identified. Among them, the majority (69 of 94) were A. thaliana lineage specific. This result indicates that the array based CGH approach may be used to identify candidates of duplication in other plant genera containing closely related species, such as Oryza, particularly for the AA genome species. We compared the degree of gene duplication through retrotransposon between O. sativa and A. thaliana and found a strikingly higher number of chimera retroposed genes in rice. The higher rate of gene duplication through retroposition and other mechanisms may indicate that the grass species is able to adapt to more diverse environments.

  5. Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

    Directory of Open Access Journals (Sweden)

    Ping Zhou, Shanli Zhai, Xiang Zhou, Ping Lin, Tengfei Jiang, Xueying Hu, Yunbo Jiang, Bin Wu, Qingde Zhang, Xuewen Xu, Jin-ping Li, Bang Liu

    2011-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV infects mainly the porcine alveolar macrophages (PAMs and causes porcine reproductive and respiratory syndrome (PRRS. Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS.

  6. Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress.

    Science.gov (United States)

    Gupta, Aarti; Sarkar, Ananda K; Senthil-Kumar, Muthappa

    2016-01-01

    With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN) demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed "tailored" responses under combined stress and the time of occurrence of each stress during their concurrence has shown differences in transcriptome profile. Our results from microarray and RT-qPCR revealed regulation of 20 novel genes uniquely during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions, time of occurrence of each stress in the interaction defines the plant responses and should thus be studied explicitly. PMID:27252712

  7. Single-nucleotide polymorphism array-based karyotyping of acute promyelocytic leukemia.

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    Inés Gómez-Seguí

    Full Text Available Acute promyelocytic leukemia (APL is characterized by the t(15;17(q22;q21, but additional chromosomal abnormalities (ACA and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A 6.0 (Affymetrix in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%: 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH, being a duplication of 8(q24 (23% and a deletion of 7(q33-qter (6% the most frequent copy-number abnormalities (CNA. Four patients (8% showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24 and del(7q33-qter, ACA were infrequent (≤3% but most of them recurrent (70%. Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17 that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.

  8. Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis.

    Science.gov (United States)

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Ahr, Hans-Juergen; Dietrich, Daniel R

    2007-05-01

    Eker rats heterozygous for a dominant germline mutation in the tuberous sclerosis 2 (Tsc2) tumor suppressor gene were used as a model to study renal carcinogenesis. Eker and corresponding wild-type rats were exposed to genotoxic aristolochic acid (AA) or non-genotoxic ochratoxin A (OTA) to elucidate early carcinogen-specific gene expression changes and to test whether Eker rats are more sensitive to carcinogen-induced changes in gene expression. Male Eker and wild-type rats were gavaged daily with AA (10 mg/kg body weight) or OTA (210 microg/kg body weight). After 1, 3, 7, and 14 days of exposure, renal histopathology, tubular cell proliferation, and Affymetrix gene expression profiles from renal cortex/outer medulla were analyzed. AA-treated Eker and wild-type rats were qualitatively comparable in all variables assessed, suggesting a Tsc2-independent mechanism of action. OTA treatment resulted in slightly increased cortical pathology and significantly elevated cell proliferation in both strains, although Eker rats were more sensitive. Deregulated genes involved in the phosphatidylinositol 3-kinase-AKT-Tsc2-mammalian target of rapamycin signaling, among other important genes prominent in tumorigenesis, in conjunction with the enhanced cell proliferation and presence of preneoplastic lesions suggested involvement of Tsc2 in OTA-mediated toxicity and carcinogenicity, especially as deregulation of genes involved in this pathway was more prominent in the Tsc2 mutant Eker rat. PMID:17483316

  9. Gene expression profile of oligodendrocytes in vitro in early stage after ionizing irradiation

    International Nuclear Information System (INIS)

    Objective: To characterize the gene expression in acute phase of irradiated oligodendrocytes (OL) in vitro. Methods: The total RNA was extracted from irradiated OLs with 10 Gy by 6 MV X-rays at 1 and 4 h. The Affymetrix RAT 230 2.0 microarray were used to evaluate and screen the gene expression profile. The quantitative real-time RT-PCR was performed to validate the microarray results of selected myelin basic protein (MBP) and neural cell adhesion molecule 1 (NCAM-1) genes. Results: Compared with un-irradiated OLs, there were 1079 different expressed genes in irradiated cells. Those genes were classified in 79 categories based on the functional classification. Some familiar genes associated with OL cellular physiological process, apoptosis, cell cycle control, metabolism, cell communication and receptor binding were included. Compared with the microarray results, the coincidence rate of real-time RT-PCR was 91.7%. The down-regulation of MBP and up-regulation of NCAM 1 gene expression were confirmed. Conclusions: Radiation-induced changes in gene expression in OLs took place in acute phase and influenced by time-course. The changes of MBP and NCAM 1 gene expression may play a key role in the pathogenesis of radiation-induced demyelination. (authors)

  10. FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder

    International Nuclear Information System (INIS)

    While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon

  11. Transcriptional Analyses of Mandarins Seriously Infected by 'Candidatus Liberibacter asiaticus'.

    Science.gov (United States)

    Xu, Meirong; Li, Ya; Zheng, Zheng; Dai, Zehan; Tao, Yang; Deng, Xiaoling

    2015-01-01

    A range of leaf symptoms, including blotchy mottle, yellowing, and small, upright leaves with a variety of chlorotic patterns resembling those induced by zinc deficiencies, are associated with huanglongbing (HLB, yellow shoot disease), a worldwide destructive citrus disease. HLB is presumably caused by the phloem-limited fastidious prokaryotic α-proteobacterium 'Candidatus Liberibacter spp.' Previous studies focused on the proteome and transcriptome analyses of citrus 5 to 35 weeks after 'Ca. L. spp.' inoculation. In this study, gene expression profiles were analyzed from mandarin Citrus reticulate Blanco cv. jiaogan leaves after a 2 year infection with 'Ca. L. asiaticus'. The Affymetrix microarray analysis explored 2,017 differentially expressed genes. Of the 1,364 genes had known functions, 938 (46.5%) were up-regulated. Genes related to photosynthesis, carbohydrate metabolic, and structure were mostly down-regulated, with rates of 92.7%, 61.0%, and 80.2%, respectively. Genes associated with oxidation-reduction and transport were mostly up-regulated with the rates of 75.0% and 64.6%, respectively. Our data analyses implied that the infection of 'Ca. L. asiaticus' could alter hormone crosstalk, inducing the jasmine acid pathway and depressing the ethylene and salicylic acid pathways in the citrus host. This study provides an enhanced insight into the host response of citrus to 'Ca. L. asiaticus' infection at a two-years infection stage. PMID:26196297

  12. Transcriptional Analyses of Mandarins Seriously Infected by 'Candidatus Liberibacter asiaticus'.

    Directory of Open Access Journals (Sweden)

    Meirong Xu

    Full Text Available A range of leaf symptoms, including blotchy mottle, yellowing, and small, upright leaves with a variety of chlorotic patterns resembling those induced by zinc deficiencies, are associated with huanglongbing (HLB, yellow shoot disease, a worldwide destructive citrus disease. HLB is presumably caused by the phloem-limited fastidious prokaryotic α-proteobacterium 'Candidatus Liberibacter spp.' Previous studies focused on the proteome and transcriptome analyses of citrus 5 to 35 weeks after 'Ca. L. spp.' inoculation. In this study, gene expression profiles were analyzed from mandarin Citrus reticulate Blanco cv. jiaogan leaves after a 2 year infection with 'Ca. L. asiaticus'. The Affymetrix microarray analysis explored 2,017 differentially expressed genes. Of the 1,364 genes had known functions, 938 (46.5% were up-regulated. Genes related to photosynthesis, carbohydrate metabolic, and structure were mostly down-regulated, with rates of 92.7%, 61.0%, and 80.2%, respectively. Genes associated with oxidation-reduction and transport were mostly up-regulated with the rates of 75.0% and 64.6%, respectively. Our data analyses implied that the infection of 'Ca. L. asiaticus' could alter hormone crosstalk, inducing the jasmine acid pathway and depressing the ethylene and salicylic acid pathways in the citrus host. This study provides an enhanced insight into the host response of citrus to 'Ca. L. asiaticus' infection at a two-years infection stage.

  13. Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.

    Science.gov (United States)

    Natella, Fausta; Leoni, Guido; Maldini, Mariateresa; Natarelli, Lucia; Comitato, Raffaella; Schonlau, Frank; Virgili, Fabio; Canali, Raffaella

    2014-01-15

    The consumption of wine and spirits, traditionally aged in oak barrels, exposes humans to roburin ingestion. These molecules belong to a class of ellagitannins (ETs), and their only known source is oak wood. Very little is currently known about roburin bioavailability and biological activity. We reported for the first time human absorption of roburins from a French oak wood (Quercus robur) water extract (Robuvit) by measuring the increase of total phenols (from 0.63 ± 0.06 to 1.26 ± 0.18 μg GAE equiv/mL plasma) and the appearance of roburin metabolites (three different glucoronidate urolithins and ellagic acid), in plasma, after 5 days of supplementation. Robuvit supplementation induced also the increase of plasma antioxidant capacity from 1.8 ± 0.05 to 1.9 ± 0.01 nmol Trolox equiv/mL plasma. Moreover, utilizing a combined ex vivo cell culture approach, we assessed the effect of Q. robur metabolites (present in human serum after supplementation) on gene expression modulation, utilizing an Affymetrix array matrix, in endothelial, neuronal, and keratinocyte cell lines. The functional analysis reveals that Robuvit metabolites affect ribosome, cell cycle, and spliceosome pathways. PMID:24354337

  14. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide.

    Science.gov (United States)

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P; Telander, David G; Hjelmeland, Leonard M; Morse, Lawrence S

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in "Circadian Rhythm Signaling" pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in "Calcium Signaling" (1 week) and "Glutamate Receptor Signaling" pathways (1 month). In contrast, dexamethasone (Dex) affected the "GABA Receptor Signaling" (1 week) and "Serotonin Receptor Signaling" (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. PMID:27429799

  15. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide

    Directory of Open Access Journals (Sweden)

    Zeljka Smit-McBride

    2016-01-01

    Full Text Available Purpose. To identify retinal pigment epithelium (RPE/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week and “Glutamate Receptor Signaling” pathways (1 month. In contrast, dexamethasone (Dex affected the “GABA Receptor Signaling” (1 week and “Serotonin Receptor Signaling” (1 month pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.

  16. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A

    2006-04-01

    Full Text Available Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6, FISH (rich in 20:5n3, 22:5n3, and 22:6n3 and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set were changed by dietary treatment (P Conclusion Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

  17. Public Availability of a Genotyped Segregating Population May Foster Marker Assisted Breeding (MAB) and Quantitative Trait Loci (QTL) Discovery: An Example Using Strawberry

    Science.gov (United States)

    Hancock, James F.; Sooriyapathirana, Suneth S.; Bassil, Nahla V.; Stegmeir, Travis; Cai, Lichun; Finn, Chad E.; Van de Weg, Eric; Weebadde, Cholani K.

    2016-01-01

    Much of the cost associated with marker discovery for marker assisted breeding (MAB) can be eliminated if a diverse, segregating population is generated, genotyped, and made available to the global breeding community. Herein, we present an example of a hybrid, wild-derived family of the octoploid strawberry that can be used by other breeding programs to economically find and tag useful genes for MAB. A pseudo test cross population between two wild species of Fragaria virginiana and F. chiloensis (FVC 11) was generated and evaluated for a set of phenotypic traits. A total of 106 individuals in the FVC 11 were genotyped for 29,251 single nucleotide polymorphisms (SNPs) utilizing a commercially available, genome-wide scanning platform (Affymetrix Axiom IStraw90TW). The marker trait associations were deduced using TASSEL software. The FVC 11 population segregating for daughters per mother, inflorescence number, inflorescence height, crown production, flower number, fruit size, yield, internal color, soluble solids, fruit firmness, and plant vigor. Coefficients of variations ranged from 10% for fruit firmness to 68% for daughters per mother, indicating an underlying quantitative inheritance for each trait. A total of 2,474 SNPs were found to be polymorphic in FVC 11 and strong marker trait associations were observed for vigor, daughters per mother, yield and fruit weight. These data indicate that FVC 11 can be used as a reference population for quantitative trait loci detection and subsequent MAB across different breeding programs and geographical locations.

  18. c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family

    Science.gov (United States)

    Dantas, Vitor G.L.; Lezirovitz, Karina; Yamamoto, Guilherme L.; Moura de Souza, Carolina Fischinger; Ferreira, Simone Gomes; Mingroni-Netto, Regina C.

    2014-01-01

    We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technology yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement using microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hearing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 variants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal dominant hereditary hearing loss and corresponds to DFNA17. The mutation identified in our study is the same described in the prior report. Thus, although linkage studies suggested a candidate gene in chromosome 14, we concluded that the mutation in chromosome 22 better explains the hearing loss phenotype in the Brazilian family. PMID:25505834

  19. High-resolution genomic analysis suggests the absence of recurrent genomic alterations other than SMARCB1 aberrations in atypical teratoid/rhabdoid tumors.

    Science.gov (United States)

    Hasselblatt, Martin; Isken, Sarah; Linge, Anna; Eikmeier, Kristin; Jeibmann, Astrid; Oyen, Florian; Nagel, Inga; Richter, Julia; Bartelheim, Kerstin; Kordes, Uwe; Schneppenheim, Reinhard; Frühwald, Michael; Siebert, Reiner; Paulus, Werner

    2013-02-01

    Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor characterized by genetic alterations affecting the SMARCB1 (hSNF5/INI1) locus in chromosome band 22q11.2. To identify potential additional genetic alterations, high-resolution genome-wide analysis was performed using a molecular inversion probe single-nucleotide polymorphism (MIP SNP) assay (Affymetrix OncoScan formalin-fixed paraffin-embedded express) on DNA isolated from 18 formalin-fixed paraffin-embedded archival samples. Alterations affecting the SMARCB1 locus could be demonstrated by MIP SNP in 15 out of 16 evaluable cases (94%). These comprised five tumors with homozygous deletions, six tumors with heterozygous deletions, and four tumors with copy number neutral loss of heterozygosity (LOH) involving chromosome band 22q11.2. Remarkably, MIB SNP analysis did not yield any further recurrent chromosomal gains, losses, or copy neutral LOH. On MIP SNP screening for somatic mutations, the presence of a SMARCB1 mutation (c.472C>T p.R158X) was confirmed, but no recurrent mutations of other cancer relevant genes could be identified. Results of fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and SMARCB1 sequencing were highly congruent with that of the MIP SNP assay. In conclusion, these data further suggest the absence of recurrent genomic alterations other than SMARCB1 in AT/RT. PMID:23074045

  20. Transcriptional Profiling of Hydrogen Production Metabolism of Rhodobacter capsulatus under Temperature Stress by Microarray Analysis.

    Science.gov (United States)

    Gürgan, Muazzez; Erkal, Nilüfer Afşar; Özgür, Ebru; Gündüz, Ufuk; Eroglu, Inci; Yücel, Meral

    2015-01-01

    Biohydrogen is a clean and renewable form of hydrogen, which can be produced by photosynthetic bacteria in outdoor large-scale photobioreactors using sunlight. In this study, the transcriptional response of Rhodobacter capsulatus to cold (4 °C) and heat (42 °C) stress was studied using microarrays. Bacteria were grown in 30/2 acetate/glutamate medium at 30 °C for 48 h under continuous illumination. Then, cold and heat stresses were applied for two and six hours. Growth and hydrogen production were impaired under both stress conditions. Microarray chips for R. capsulatus were custom designed by Affymetrix (GeneChip®. TR_RCH2a520699F). The numbers of significantly changed genes were 328 and 293 out of 3685 genes under cold and heat stress, respectively. Our results indicate that temperature stress greatly affects the hydrogen production metabolisms of R. capsulatus. Specifically, the expression of genes that participate in nitrogen metabolism, photosynthesis and the electron transport system were induced by cold stress, while decreased by heat stress. Heat stress also resulted in down regulation of genes related to cell envelope, transporter and binding proteins. Transcriptome analysis and physiological results were consistent with each other. The results presented here may aid clarification of the genetic mechanisms for hydrogen production in purple non-sulfur (PNS) bacteria under temperature stress. PMID:26086826

  1. Admixture mapping identifies introgressed genomic regions in North American canids.

    Science.gov (United States)

    vonHoldt, Bridgett M; Kays, Roland; Pollinger, John P; Wayne, Robert K

    2016-06-01

    Hybrid zones typically contain novel gene combinations that can be tested by natural selection in a unique genetic context. Parental haplotypes that increase fitness can introgress beyond the hybrid zone, into the range of parental species. We used the Affymetrix canine SNP genotyping array to identify genomic regions tagged by multiple ancestry informative markers that are more frequent in an admixed population than expected. We surveyed a hybrid zone formed in the last 100 years as coyotes expanded their range into eastern North America. Concomitant with expansion, coyotes hybridized with wolves and some populations became more wolflike, such that coyotes in the northeast have the largest body size of any coyote population. Using a set of 3102 ancestry informative markers, we identified 60 differentially introgressed regions in 44 canines across this admixture zone. These regions are characterized by an excess of exogenous ancestry and, in northeastern coyotes, are enriched for genes affecting body size and skeletal proportions. Further, introgressed wolf-derived alleles have penetrated into Southern US coyote populations. Because no wolves currently exist in this area, these alleles are unlikely to have originated from recent hybridization. Instead, they probably originated from intraspecific gene flow or ancient admixture. We show that grey wolf and coyote admixture has far-reaching effects and, in addition to phenotypically transforming admixed populations, allows for the differential movement of alleles from different parental species to be tested in new genomic backgrounds. PMID:27106273

  2. Molecular characterization of human adenomyosis.

    Science.gov (United States)

    Hever, A; Roth, R B; Hevezi, P A; Lee, J; Willhite, D; White, E C; Marin, E M; Herrera, R; Acosta, H M; Acosta, A J; Zlotnik, A

    2006-12-01

    Adenomyosis is a common gynaecological disorder characterized by the abnormal growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia. Uterine fibroids are benign neoplasms of the myometrium, and they represent a diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium. Unsupervised principal component analysis (PCA) revealed that these four tissue types could be segregated from one another solely based on their gene expression profiles. Analysis of variance (ANOVA), followed by Tukey means separation test, significance analysis of microarrays (SAM) and 2-fold change threshold, identified 7415 probe sets as differentially expressed among the four groups of samples. Supervised cluster analysis based on these probe sets clustered adenomyosis most closely with endometrium and uterine fibroids with myometrium, consistent with the anatomic origin of these two diseases. The Tukey means separation post hoc testing found 2073 probe sets altered between adenomyosis and normal endometrium or myometrium, and 2327 probe sets altered in expression when comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in uterine fibroids. Notably, the top network in both cases was associated with functions implicated in cancer and cell death. Finally, we compared the gene expression profiles of adenomyosis and uterine fibroids and identified 471 differentially expressed probe sets that may represent potential biomarkers for the differential diagnosis of these diseases. PMID:17020905

  3. Comparative Transcriptome Analysis of Two Ascophyllum nodosum Extract Biostimulants: Same Seaweed but Different.

    Science.gov (United States)

    Goñi, Oscar; Fort, Antoine; Quille, Patrick; McKeown, Peter C; Spillane, Charles; O'Connell, Shane

    2016-04-13

    Biostimulants for crop management are gaining increased attention with continued demand for increased crop yields. Seaweed extracts represent one category of biostimulant, with Ascophyllum nodosum extracts (ANE) widely used for yield and quality enhancement. This study investigated how the composition of two ANE biostimulants (ANE A and ANE B) affects plant mRNA transcriptomes, using the model plant Arabidopsis thaliana. Using Affymetrix Ath1 microarrays, significant heterogeneity was detected between the ANE biostimulants in terms of their impacts on the mRNA transcriptome of A. thaliana plants, which accumulated significantly more biomass than untreated controls. Genes dysregulated by the ANE biostimulants are associated with a wide array of predicted biological processes, molecular functions, and subcellular distributions. ANE A dysregulated 4.47% of the transcriptome, whereas ANE B dysregulated 0.87%. The compositions of both ANEs were significantly different, with a 4-fold difference in polyphenol levels, the largest observed. The standardization of the composition of ANE biostimulants represents a challenge for providing consistent effects on plant gene expression and biostimulation. PMID:27010818

  4. Genome-Wide Association Study of Antiphospholipid Antibodies

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    M. Ilyas Kamboh

    2013-01-01

    Full Text Available Background. The persistent presence of antiphospholipid antibodies (APA may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL, lupus anticoagulant (LAC, and anti-β2 glycoprotein I antibodies (anti-β2GPI. Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs. Association of SNPs with the antibody status (positive/negative was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with P

  5. Changes in skeletal muscle gene expression following clenbuterol administration

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    McIntyre Lauren M

    2006-12-01

    Full Text Available Abstract Background Beta-adrenergic receptor agonists (BA induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P P Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle.

  6. Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Stefanie Meyer; Ilja Hagen; Bernd Becker; Alexander Roesch; Michael Landthaler; Thomas Vogt

    2005-01-01

    AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells.METHODS: Upon stimulation of ephrin-B pathways in IFC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy.RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes.Furthermore, we show that the expression of repairrelated genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution.CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

  7. Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.

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    Rani E George

    Full Text Available BACKGROUND: Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP array. FINDINGS: Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%. Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016. Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95% and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case. CONCLUSIONS: This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy.

  8. Identification and validation of quantitative trait loci (QTL for canine hip dysplasia (CHD in German Shepherd Dogs.

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    Lena Fels

    Full Text Available Canine hip dysplasia (CHD is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were <0.1%. Genotype effects of these SNPs explained 20-32% of the phenotypic variance of CHD in German Shepherd Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL and a novel QTL for CHD in German Shepherd Dogs.

  9. Next generation sequencing in synovial sarcoma reveals novel gene mutations.

    Science.gov (United States)

    Vlenterie, Myrella; Hillebrandt-Roeffen, Melissa H S; Flucke, Uta E; Groenen, Patricia J T A; Tops, Bastiaan B J; Kamping, Eveline J; Pfundt, Rolph; de Bruijn, Diederik R H; Geurts van Kessel, Ad H M; van Krieken, Han J H J M; van der Graaf, Winette T A; Versleijen-Jonkers, Yvonne M H

    2015-10-27

    Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18), however, they show heterogeneous clinical behavior. We analyzed multiple SS to reveal additional genetic alterations besides the translocation. Twenty-six SS from 22 patients were sequenced for 409 cancer-related genes using the Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform. The detected variants were verified by Sanger sequencing and compared to matched normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan array (Affymetrix, USA). In total, eight somatic mutations were detected in eight samples. These mutations have not been reported previously in SS. Two of these, in KRAS and CCND1, represent known oncogenic mutations in other malignancies. Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4. DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was found in a metastatic lesion progressing under pazopanib, but not in the responding lesion. Our results emphasize t(X;18) as a single initiating event in SS and as the main oncogenic driver. Our results also show the occurrence of additional genetic events, mutations or chromosomal aberrations, occurring more frequently in SS with an onset in adults. PMID:26415226

  10. Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome

    Science.gov (United States)

    Mlynarski, Elisabeth E.; Xie, Michael; Taylor, Deanne; Sheridan, Molly B.; Guo, Tingwei; Racedo, Silvia E.; McDonald-McGinn, Donna M.; Chow, Eva W. C.; Vorstman, Jacob; Swillen, Ann; Devriendt, Koen; Breckpot, Jeroen; Digilio, Maria Cristina; Marino, Bruno; Dallapiccola, Bruno; Philip, Nicole; Simon, Tony J.; Roberts, Amy E.; Piotrowicz, Małgorzata; Bearden, Carrie E.; Eliez, Stephan; Gothelf, Doron; Coleman, Karlene; Kates, Wendy R.; Devoto, Marcella; Zackai, Elaine; Heine-Suñer, Damian; Goldmuntz, Elizabeth; Bassett, Anne S.; Morrow, Bernice E.

    2016-01-01

    The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60–75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients. PMID:26742502

  11. Allele-Skewed DNA Modification in the Brain: Relevance to a Schizophrenia GWAS.

    Science.gov (United States)

    Gagliano, Sarah A; Ptak, Carolyn; Mak, Denise Y F; Shamsi, Mehrdad; Oh, Gabriel; Knight, Joanne; Boutros, Paul C; Petronis, Arturas

    2016-05-01

    Numerous recent studies have suggested that phenotypic effects of DNA sequence variants can be mediated or modulated by their epigenetic marks, such as allele-skewed DNA modification (ASM). Using Affymetrix SNP microarrays, we performed a comprehensive search of ASM effects in human post-mortem brain and sperm samples (total n = 256) from individuals with major psychosis and control individuals. Depending on the phenotypic category of the brain samples, 1.4%-7.5% of interrogated SNPs exhibited ASM effects. Next, we investigated ASM in the context of genetic studies of schizophrenia and detected that brain ASM SNPs were significantly overrepresented among sub-threshold SNPs from a schizophrenia genome-wide association study (GWAS). Brain ASM SNPs showed a much stronger enrichment in a schizophrenia GWAS than in 17 large GWASs of non-psychiatric diseases and traits, arguing that ASM effects are at least partially tissue specific. Studies of germline and control brain ASM SNPs supported a causal association between ASM and schizophrenia. Finally, significantly higher proportions of ASM SNPs than of non-ASM SNPs were detected at loci exhibiting epigenetic signatures of enhancers and promoters, and they were overrepresented within transcription factor binding regions and DNase I hypersensitive sites. All of these findings collectively indicate that ASM SNPs should be prioritized in follow-up GWASs. PMID:27087318

  12. Defining the genomic signature of the parous breast

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    Peri Suraj

    2012-10-01

    Full Text Available Abstract Background It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy. Methods In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P and 42 nulliparous (NP healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry. Results We identified 305 differentially expressed probesets (208 distinct genes. Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis. Conclusions This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

  13. Molecular profiling of the lateral habenula in a rat model of depression.

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    Trine Christensen

    Full Text Available OBJECTIVE: This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level. METHODS: Rat whole genome expression chips (Affymetrix were used to detect gene expression regulations in the lateral habenula of rats subjected to chronic mild stress (mild stressors exchanged twice a day for 8 weeks. Some rats received antidepressant treatment during fifth to eights week of CMS. The lateral habenula gene expression profile was studied through the gene ontology and signal pathway analyses using bioinformatics. Real-time quantitative polymerase chain reaction (RT-PCR was used to verify the microarray results and determine the expression of the Fcrla, Eif3k, Sec3l1, Ubr5, Abca8a, Ankrd49, Cyp2j10, Frs3, Syn2, and Znf503 genes in the lateral habenula tissue. RESULTS: In particular we found that stress and antidepressant treatment affected intracellular cascades like growth factor receptor signaling, G-protein-coupled receptor signaling, and Wnt signaling - processes involved in the neuroplastic changes observed during the progression of depression and antidepressant treatment. CONCLUSION: The present study suggests an important role of the lateral habenula in the development of depression-like conditions and correlates to previous studies demonstrating a significant role of the lateral habenula in depressive-like conditions and antidepressant treatment.

  14. Different transcriptional response to Xanthomonas citri subsp. citri between kumquat and sweet orange with contrasting canker tolerance.

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    Xing-Zheng Fu

    Full Text Available Citrus canker disease caused by Xanthomonas citri subsp. citri (Xcc is one of the most devastating biotic stresses affecting the citrus industry. Meiwa kumquat (Fortunella crassifolia is canker-resistant, while Newhall navel orange (Citrus sinensis Osbeck is canker-sensitive. To understand the molecular mechanisms underlying the differences in responses to Xcc, transcriptomic profiles of these two genotypes following Xcc attack were compared by using the Affymetrix citrus genome GeneChip. A total of 794 and 1324 differentially expressed genes (DEGs were identified as canker-responsive genes in Meiwa and Newhall, respectively. Of these, 230 genes were expressed in common between both genotypes, while 564 and 1094 genes were only significantly expressed in either Meiwa or Newhall. Gene ontology (GO annotation and Singular Enrichment Analysis (SEA of the DEGs showed that genes related to the cell wall and polysaccharide metabolism were induced for basic defense in both Meiwa and Newhall, such as chitinase, glucanase and thaumatin-like protein. Moreover, apart from inducing basic defense, Meiwa showed specially upregulated expression of several genes involved in the response to biotic stimulus, defense response, and cation binding as comparing with Newhall. And in Newhall, abundant photosynthesis-related genes were significantly down-regulated, which may be in order to ensure the basic defense. This study revealed different molecular responses to canker disease in Meiwa and Newhall, affording insight into the response to canker and providing valuable information for the identification of potential genes for engineering canker tolerance in the future.

  15. Transformation of metabolism with age and lifestyle in Antarctic seals: a case study of systems biology approach to cross-species microarray experiment

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    Schlater Amber

    2010-09-01

    Full Text Available Abstract Background The metabolic transformation that changes Weddell seal pups born on land into aquatic animals is not only interesting for the study of general biology, but it also provides a model for the acquired and congenital muscle disorders which are associated with oxygen metabolism in skeletal muscle. However, the analysis of gene expression in seals is hampered by the lack of specific microarrays and the very limited annotation of known Weddell seal (Leptonychotes weddellii genes. Results Muscle samples from newborn, juvenile, and adult Weddell seals were collected during an Antarctic expedition. Extracted RNA was hybridized on Affymetrix Human Expression chips. Preliminary studies showed a detectable signal from at least 7000 probe sets present in all samples and replicates. Relative expression levels for these genes was used for further analysis of the biological pathways implicated in the metabolism transformation which occurs in the transition from newborn, to juvenile, to adult seals. Cytoskeletal remodeling, WNT signaling, FAK signaling, hypoxia-induced HIF1 activation, and insulin regulation were identified as being among the most important biological pathways involved in transformation. Conclusion In spite of certain losses in specificity and sensitivity, the cross-species application of gene expression microarrays is capable of solving challenging puzzles in biology. A Systems Biology approach based on gene interaction patterns can compensate adequately for the lack of species-specific genomics information.

  16. Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression

    International Nuclear Information System (INIS)

    Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations. Total RNA was isolated from 29 frozen gastric GISTs and processed for hybridization on GENECHIP® HG-U133 Plus 2.0 microarrays (Affymetrix). KIT and PDGFRA were analyzed by sequencing, while related mRNA levels were analyzed by quantitative RT-PCR. Fifteen and eleven tumours possessed mutations in KIT and PDGFRA, respectively; no mutation was found in three tumours. Gene expression analysis identified no discriminative profiles associated with clinical or pathological parameters, even though expression of hundreds of genes differentiated tumour receptor mutation and expression status. Functional features of genes differentially expressed between the two groups of GISTs suggested alterations in angiogenesis and G-protein-related and calcium signalling. Our study has identified novel molecular elements likely to be involved in receptor-dependent GIST development and allowed confirmation of previously published results. These elements may be potential therapeutic targets and novel markers of KIT mutation status

  17. A single-nucleotide polymorphism-based approach for rapid and cost-effective genetic wolf monitoring in Europe based on noninvasively collected samples.

    Science.gov (United States)

    Kraus, Robert H S; vonHoldt, Bridgett; Cocchiararo, Berardino; Harms, Verena; Bayerl, Helmut; Kühn, Ralph; Förster, Daniel W; Fickel, Jörns; Roos, Christian; Nowak, Carsten

    2015-03-01

    Noninvasive genetics based on microsatellite markers has become an indispensable tool for wildlife monitoring and conservation research over the past decades. However, microsatellites have several drawbacks, such as the lack of standardisation between laboratories and high error rates. Here, we propose an alternative single-nucleotide polymorphism (SNP)-based marker system for noninvasively collected samples, which promises to solve these problems. Using nanofluidic SNP genotyping technology (Fluidigm), we genotyped 158 wolf samples (tissue, scats, hairs, urine) for 192 SNP loci selected from the Affymetrix v2 Canine SNP Array. We carefully selected an optimised final set of 96 SNPs (and discarded the worse half), based on assay performance and reliability. We found rates of missing data in this SNP set of <10% and genotyping error of ~1%, which improves genotyping accuracy by nearly an order of magnitude when compared to published data for other marker types. Our approach provides a tool for rapid and cost-effective genotyping of noninvasively collected wildlife samples. The ability to standardise genotype scoring combined with low error rates promises to constitute a major technological advancement and could establish SNPs as a standard marker for future wildlife monitoring. PMID:25042673

  18. A bi-functional xyloglucan galactosyltransferase is an indispensable salt stress tolerance determinant in arabidop

    KAUST Repository

    Li, Wenbo

    2013-07-01

    Salinity is an abiotic stress that substantially limits crop production worldwide. To identify salt stress tolerance determinants, we screened for Arabidopsis mutants that are hypersensitive to salt stress and designated these mutants as short root in salt medium (rsa). One of these mutants, rsa3-1, is hypersensitive to NaCl and LiCl but not to CsCl or to general osmotic stress. Reactive oxygen species (ROS) over-accumulate in rsa3-1 plants under salt stress. Gene expression profiling with Affymetrix microarray analysis revealed that RSA3 controls expression of many genes including genes encoding proteins for ROS detoxification under salt stress. Map-based cloning showed that RSA3 encodes a xyloglucan galactosyltransferase, which is allelic to a gene previously named MUR3/KAM1. The RSA3/ MUR3/KAM1-encoded xylogluscan galactosyltransferase regulates actin microfilament organization (and thereby contributes to endomembrane distribution) and is also involved in cell wall biosynthesis. In rsa3-1, actin cannot assemble and form bundles as it does in the wild-type but instead aggregates in the cytoplasm. Furthermore, addition of phalloidin, which prevents actin depolymerization, can rescue salt hypersensitivity of rsa3-1. Together, these results suggest that RSA3/MUR3/KAM1 along with other cell wall-associated proteins plays a critical role in salt stress tolerance by maintaining the proper organization of actin microfilaments in order to minimize damage caused by excessive ROS. © 2013 The Author.

  19. Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

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    Anna Rosell

    Full Text Available BACKGROUND: Spontaneous intracerebral hemorrhage (ICH represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. METHODOLOGY/PRINCIPAL FINDINGS: Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH and the corresponding contralateral white (CW and grey (CG matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed. The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results. CONCLUSIONS: The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.

  20. A robust method for the amplification of RNA in the sense orientation

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    Quackenbush John

    2005-03-01

    Full Text Available Abstract Background Small quantities of RNA (1–4 μg total RNA available from biological samples frequently require a single round of amplification prior to analysis, but current amplification strategies have limitations that may restrict their usefulness in downstream genomic applications. The Eberwine amplification method has been extensively validated but is limited by its ability to produce only antisense RNA. Alternatives lack extensive validation and are often confounded by problems with bias or yield attributable to their greater biological and technical complexity. Results To overcome these limitations, we have developed a straightforward and robust protocol for amplification of RNA in the sense orientation. This protocol is based upon Eberwine's method but incorporates elements of more recent amplification techniques while avoiding their complexities. Our technique yields greater than 100-fold amplification, generates long transcript, and produces mRNA that is well suited for use with microarray applications. Microarrays performed with RNA amplified using this protocol demonstrate minimal amplification bias and high reproducibility. Conclusion The protocol we describe here is readily adaptable for the production of sense or antisense, labeled or unlabeled RNA from intact or partially-degraded prokaryotic or eukaryotic total RNA. The method outperforms several commercial RNA amplification kits and can be used in conjunction with a variety of microarray platforms, such as cDNA arrays, oligonucleotide arrays, and Affymetrix GeneChip™ arrays.

  1. Transport and characterization of ambient biological aerosol near Laurel, MD

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    J. L. Santarpia

    2010-09-01

    Full Text Available Bacterial aerosol have been observed and studied in the ambient environment since the mid nineteenth century. These studies have sought to provide a better understanding of the diversity, variability and factors that control the biological aerosol population. In this study, we show comparisons between diversity of culturable bacteria and fungi, using culture and clinical biochemical tests, and 16S rRNA diversity using Affymetrix PhyloChips. Comparing the culturable fraction and surveying the total 16S rRNA of each sample provides a comprehensive look at the bacterial population studied and allows comparison with previous studies. Thirty-six hour back-trajectories of the air parcels sampled, over the two day period beginning 4 November 2008, provide information on the sources of aerosol sampled on the campus of Johns Hopkins University Applied Physics Laboratory in Laurel, MD. This study indicates that back-trajectory modeling of air parcels may provide insights into the observed diversity of biological aerosol.

  2. Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis

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    Holger G Hass, Oliver Nehls, Juergen Jobst, Andrea Frilling, Ulrich Vogel, Stephan Kaiser

    2008-04-01

    Full Text Available AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.METHODS: Oligonucleotide arrays (Affymetrix U133A were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding non-malignant liver tissue. To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated; P 2; ≥ 70% were identified. Using these data and two-dimensional cluster analysis, a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling. The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100% encoded osteopontin. Furthermore, an association of various genes with the histopathological grading could be demonstrated.CONCLUSION: A highly specific gene expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against non-malignant liver tissue and other liver masses. The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin. These data may lead to a better understanding of human cholangiocarcinogenesis.

  3. Genome-wide mapping of copy number variation in humans: comparative analysis of high resolution array platforms.

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    Rajini R Haraksingh

    Full Text Available Accurate and efficient genome-wide detection of copy number variants (CNVs is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH, Single Nucleotide Polymorphism (SNP genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications.

  4. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    Science.gov (United States)

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  5. Genome-wide Expression Profiling in Seedlings of the Arabidopsis Mutant uro that is Defective in the Secondary Cell Wall Formation

    Institute of Scientific and Technical Information of China (English)

    Zheng Yuan; Xuan Yao; Dabing Zhang; Yue Sun; Hai Huang

    2007-01-01

    Plant secondary growth is of tremendous importance, not only for plant growth and development but also for economic usefulness.Secondary tissues such as xylem and phloem are the conducting tissues in plant vascular systems, essentially for water and nutrient transport, respectively.On the other hand, products of plant secondary growth are important raw materials and renewable sources of energy.Although advances have been recently made towards describing molecular mechanisms that regulate secondary growth, the genetic control for this process is not yet fully understood.Secondary cell wall formation in plants shares some common mechanisms with other plant secondary growth processes.Thus, studies on the secondary cell wall formation using Arabidopsis may help to understand the regulatory mechanisms for plant secondary growth.We previously reported phenotypic characterizations of an Arabidopsis semi-dominant mutant,upright rosette (uro), which is defective in secondary cell wall growth and has an unusually soft stem.Here, we show that lignification in the secondary cell wall in uro is aberrant by analyzing hypocotyl and stem.We also show genome-wide expression profiles of uro seedlings, using the Affymetrix GeneChip that contains approximately 24 000 Arabidopsis genes.Genes identified with altered expression levels include those that function in plant hormone biosynthesis and signaling,cell division and plant secondary tissue growth.These results provide useful information for further characterizations of the regulatory network in plant secondary cell wall formation.

  6. Altered neuronatin expression in the rat dorsal root ganglion after sciatic nerve transection

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    Wu Chih-Hsien

    2010-05-01

    Full Text Available Abstract Background Several molecular changes occur following axotomy, such as gene up-regulation and down-regulation. In our previous study using Affymetrix arrays, it was found that after the axotomy of sciatic nerve, there were many novel genes with significant expression changes. Among them, neuronatin (Nnat was the one which expression was significantly up-regulated. Nnat was identified as a gene selectively expressed in neonatal brains and markedly reduced in adult brains. The present study investigated whether the expression of Nnat correlates with symptoms of neuropathic pain in adult rats with transected sciatic nerve. Methods Western blotting, immunohistochemistry, and the Randall and Selitto test were used to study the protein content, and subcellular localization of Nnat in correlation with pain-related animal behavior. Results It was found that after nerve injury, the expression of Nnat was increased in total protein extracts. Unmyelinated C-fiber and thinly myelinated A-δ fiber in adult dorsal root ganglions (DRGs were the principal sub-population of primary afferent neurons with distributed Nnat. The increased expression of Nnat and its subcellular localization were related to mechanical hyperalgesia. Conclusions The results indicated that there was significant correlation between mechanical hyperalgesia in axotomy of sciatic nerve and the increased expression of Nnat in C-fiber and A-δ fiber of adult DRG neurons.

  7. Histatin-1 Expression in Human Lacrimal Epithelium.

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    Dhara Shah

    Full Text Available Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature.We utilized human Muller's muscle conjunctival resection (MMCR specimens containing accessory lacrimal gland (ALG and cadaveric main lacrimal gland (MLG as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM. Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad and alpha-smooth muscle actin (ASMA. Reverse transcriptase polymerase chain reaction (RT-PCR analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG.Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers.Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies.

  8. Spermidine affects the transcriptome responses to high temperature stress in ripening tomato fruit

    Institute of Scientific and Technical Information of China (English)

    Lin CHENG; Rong-rong SUN; Fei-yan WANG; Zhen PENG; Fu-ling KONG; Jian WU; Jia-shu CAO; Gang LU

    2012-01-01

    Objective:High temperature adversely affects quality and yield of tomato fruit.Polyamine can alleviate heat injury in plants.This study is aimed to investigate the effects of polyamine and high temperature on transcriptional profiles in ripening tomato fruit.Methods:An Affymetrix tomato microarray was used to evaluate changes in gene expression in response to exogenous spermidine (Spd,1 mmol/L) and high temperature (33/27 ℃) treatments in tomato fruits at mature green stage.Results:Of the 10101 tomato probe sets represented on the array,127 loci were differentially expressed in high temperature-treated fruits,compared with those under normal conditions,functionally characterized by their involvement in signal transduction,defense responses,oxidation reduction,and hormone responses.However,only 34 genes were up-regulated in Spd-treated fruits as compared with non-treated fruits,which were involved in primary metabolism,signal transduction,hormone responses,transcription factors,and stress responses.Meanwhile,55 genes involved in energy metabolism,cell wall metabolism,and photosynthesis were down-regulated in Spd-treated fruits.Conclusions:Our results demonstrated that Spd might play an important role in regulation of tomato fruit response to high temperature during ripening stage.

  9. New aQTL SNPs for the CYP2D6 Identified by a Novel Mediation Analysis of Genome-Wide SNP Arrays, Gene Expression Arrays, and CYP2D6 Activity

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    Guanglong Jiang

    2013-01-01

    Full Text Available Background. The genome-wide association studies (GWAS have been successful during the last few years. A key challenge is that the interpretation of the results is not straightforward, especially for transacting SNPs. Integration of transcriptome data into GWAS may provide clues elucidating the mechanisms by which a genetic variant leads to a disease. Methods. Here, we developed a novel mediation analysis approach to identify new expression quantitative trait loci (eQTL driving CYP2D6 activity by combining genotype, gene expression, and enzyme activity data. Results. 389,573 and 1,214,416 SNP-transcript-CYP2D6 activity trios are found strongly associated (P<10-5, FDR=16.6% and 11.7% for two different genotype platforms, namely, Affymetrix and Illumina, respectively. The majority of eQTLs are trans-SNPs. A single polymorphism leads to widespread downstream changes in the expression of distant genes by affecting major regulators or transcription factors (TFs, which would be visible as an eQTL hotspot and can lead to large and consistent biological effects. Overlapped eQTL hotspots with the mediators lead to the discovery of 64 TFs. Conclusions. Our mediation analysis is a powerful approach in identifying the trans-QTL-phenotype associations. It improves our understanding of the functional genetic variations for the liver metabolism mechanisms.

  10. Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.

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    Akiko Shiotani

    Full Text Available BACKGROUND: Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established. AIM: To investigate pharmacogenomic profile of low dose aspirin (LDA-induced small bowel bleeding. METHODS: Genome-wide analysis of single nucleotide polymorphisms (SNPs was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing. RESULTS: In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463 GG (p=0.003, CYP2D6 (rs28360521 GG (p=0.02, CYP24A1 (rs4809957 T allele (p=0.04, and GSTP1 (rs1695 G allele (p=0.04 were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521 GG (OR 4.11, 95% CI. 1.62 -10.4 was associated with small bowel bleeding. CONCLUSIONS: CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.

  11. Web-based analysis of the mouse transcriptome using Genevestigator

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    Gruissem Wilhelm

    2006-06-01

    Full Text Available Abstract Background Gene function analysis often requires a complex and laborious sequence of laboratory and computer-based experiments. Choosing an effective experimental design generally results from hypotheses derived from prior knowledge or experimentation. Knowledge obtained from meta-analyzing compendia of expression data with annotation libraries can provide significant clues in understanding gene and network function, resulting in better hypotheses that can be tested in the laboratory. Description Genevestigator is a microarray database and analysis system allowing context-driven queries. Simple but powerful tools allow biologists with little computational background to retrieve information about when, where and how genes are expressed. We manually curated and quality-controlled 3110 mouse Affymetrix arrays from public repositories. Data queries can be run against an annotation library comprising 160 anatomy categories, 12 developmental stage groups, 80 stimuli, and 182 genetic backgrounds or modifications. The quality of results obtained through Genevestigator is illustrated by a number of biological scenarios that are substantiated by other types of experimentation in the literature. Conclusion The Genevestigator-Mouse database effectively provides biologically meaningful results and can be accessed at https://www.genevestigator.ethz.ch.

  12. Unsupervised assessment of microarray data quality using a Gaussian mixture model

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    Sick Beate

    2009-06-01

    Full Text Available Abstract Background Quality assessment of microarray data is an important and often challenging aspect of gene expression analysis. This task frequently involves the examination of a variety of summary statistics and diagnostic plots. The interpretation of these diagnostics is often subjective, and generally requires careful expert scrutiny. Results We show how an unsupervised classification technique based on the Expectation-Maximization (EM algorithm and the naïve Bayes model can be used to automate microarray quality assessment. The method is flexible and can be easily adapted to accommodate alternate quality statistics and platforms. We evaluate our approach using Affymetrix 3' gene expression and exon arrays and compare the performance of this method to a similar supervised approach. Conclusion This research illustrates the efficacy of an unsupervised classification approach for the purpose of automated microarray data quality assessment. Since our approach requires only unannotated training data, it is easy to customize and to keep up-to-date as technology evolves. In contrast to other "black box" classification systems, this method also allows for intuitive explanations.

  13. High-throughput gene expression profiling of memory differentiation in primary human T cells

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    Russell Kate

    2008-08-01

    Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

  14. MegaSNPHunter: a learning approach to detect disease predisposition SNPs and high level interactions in genome wide association study

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    Xue Hong

    2009-01-01

    Full Text Available Abstract Background The interactions of multiple single nucleotide polymorphisms (SNPs are highly hypothesized to affect an individual's susceptibility to complex diseases. Although many works have been done to identify and quantify the importance of multi-SNP interactions, few of them could handle the genome wide data due to the combinatorial explosive search space and the difficulty to statistically evaluate the high-order interactions given limited samples. Results Three comparative experiments are designed to evaluate the performance of MegaSNPHunter. The first experiment uses synthetic data generated on the basis of epistasis models. The second one uses a genome wide study on Parkinson disease (data acquired by using Illumina HumanHap300 SNP chips. The third one chooses the rheumatoid arthritis study from Wellcome Trust Case Control Consortium (WTCCC using Affymetrix GeneChip 500K Mapping Array Set. MegaSNPHunter outperforms the best solution in this area and reports many potential interactions for the two real studies. Conclusion The experimental results on both synthetic data and two real data sets demonstrate that our proposed approach outperforms the best solution that is currently available in handling large-scale SNP data both in terms of speed and in terms of detection of potential interactions that were not identified before. To our knowledge, MegaSNPHunter is the first approach that is capable of identifying the disease-associated SNP interactions from WTCCC studies and is promising for practical disease prognosis.

  15. Transcriptome Analysis of Induced Systemic Drought Tolerance Elicited by Pseudomonas chlororaphis O6 in Arabidopsis thaliana

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    Song-Mi Cho

    2013-06-01

    Full Text Available Root colonization by Pseudomonas chlororaphis O6 induces systemic drought tolerance in Arabidopsis thaliana. Microarray analysis was performed using the 22,800-gene Affymetrix GeneChips to identify differentially-expressed genes from plants colonized with or without P. chlororaphis O6 under drought stressed conditions or normal growth conditions. Root colonization in plants grown under regular irrigation condition increased transcript accumulation from genes associated with defense, response to reactive oxygen species, and auxin- and jasmonic acid-responsive genes, but decreased transcription factors associated with ethylene and abscisic acid signaling. The cluster of genes involved in plant disease resistance were up-regulated, but the set of drought signaling response genes were down-regulated in the P. chlororaphis O6-colonized under drought stress plants compared to those of the drought stressed plants without bacterial treatment. Transcripts of the jasmonic acid-marker genes, VSP1 and pdf-1.2, the salicylic acid regulated gene, PR-1, and the ethylene-response gene, HEL, also were up-regulated in plants colonized by P. chlororaphis O6, but differed in their responsiveness to drought stress. These data show how gene expression in plants lacking adequate water can be remarkably influenced by microbial colonization leading to plant protection, and the activation of the plant defense signal pathway induced by root colonization of P. chlororaphis O6 might be a key element for induced systemic tolerance by microbes.

  16. The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence.

    Science.gov (United States)

    Musci, Rashelle J; Masyn, Katherine E; Benke, Kelly; Maher, Brion; Uhl, George; Ialongo, Nicholas S

    2016-02-01

    Internalizing symptoms during adolescence and beyond is a major public health concern, particularly because severe symptoms can lead to the diagnosis of a number of serious psychiatric conditions. This study utilizes a unique sample with a complex statistical method in order to explore Gene × Environment interactions found in internalizing symptoms during adolescence. Data for this study were drawn from a longitudinal prevention intervention study (n = 798) of Baltimore city school children. Internalizing symptom data were collected using self-report and blood or saliva samples genotyped using Affymetrix 6.0 microarrays. A major depression polygenic score was created for each individual using information from the major depressive disorder Psychiatric Genetics Consortium and used as a predictor in a latent trait-state-occasion model. The major depressive disorder polygenic score was a significant predictor of the stable latent trait variable, which captures time-independent phenotypic variability. In addition, an early childhood stressor of death or divorce was a significant predictor of occasion-specific variables. A Gene × Environment interaction was not a significant predictor of the latent trait or occasion variables. These findings support the importance of genetics on the stable latent trait portion of internalizing symptoms across adolescence. PMID:25936925

  17. Insulin and glucose play a role in foam cell formation and function

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    Keller Susanna R

    2006-06-01

    Full Text Available Abstract Background Foam cell formation in diabetic patients often occurs in the presence of high insulin and glucose levels. To test whether hyperinsulinemic hyperglycemic conditions affect foam cell differentiation, we examined gene expression, cytokine production, and Akt phosphorylation in human monocyte-derived macrophages incubated with two types of oxidized low density lipoprotein (LDL, minimally modified LDL (mmLDL and extensively oxidized LDL (OxLDL. Methods and results Using Affymetrix GeneChip® arrays, we found that several genes directly related to insulin signaling were changed. The insulin receptor and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL, whereas insulin-induced gene 1 was significantly down-regulated. In hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt phosphorylation and expression of the insulin-regulated aminopeptidase. The level of proinflammatory cytokines, IL-lβ, IL-12, and IL-6, and of a 5-lipoxygenase eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE, was also increased. Conclusion These results suggest that the exposure of macrophages to modified low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects insulin signaling and promotes the release of proinflammatory stimuli, such as cytokines and eicosanoids. These in turn may contribute to the development of insulin resistance.

  18. Whole genome distribution and ethnic differentiation of copy number variation in Caucasian and Asian populations.

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    Jian Li

    Full Text Available Although copy number variation (CNV has recently received much attention as a form of structure variation within the human genome, knowledge is still inadequate on fundamental CNV characteristics such as occurrence rate, genomic distribution and ethnic differentiation. In the present study, we used the Affymetrix GeneChip(R Mapping 500K Array to discover and characterize CNVs in the human genome and to study ethnic differences of CNVs between Caucasians and Asians. Three thousand and nineteen CNVs, including 2381 CNVs in autosomes and 638 CNVs in X chromosome, from 985 Caucasian and 692 Asian individuals were identified, with a mean length of 296 kb. Among these CNVs, 190 had frequencies greater than 1% in at least one ethnic group, and 109 showed significant ethnic differences in frequencies (p<0.01. After merging overlapping CNVs, 1135 copy number variation regions (CNVRs, covering approximately 439 Mb (14.3% of the human genome, were obtained. Our findings of ethnic differentiation of CNVs, along with the newly constructed CNV genomic map, extend our knowledge on the structural variation in the human genome and may furnish a basis for understanding the genomic differentiation of complex traits across ethnic groups.

  19. Assessment of bagging GBLUP for whole-genome prediction of broiler chicken traits.

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    Abdollahi-Arpanahi, R; Morota, G; Valente, B D; Kranis, A; Rosa, G J M; Gianola, D

    2015-06-01

    Bootstrap aggregation (bagging) is a resampling method known to produce more accurate predictions when predictors are unstable or when the number of markers is much larger than sample size, because of variance reduction capabilities. The purpose of this study was to compare genomic best linear unbiased prediction (GBLUP) with bootstrap aggregated sampling GBLUP (Bagged GBLUP, or BGBLUP) in terms of prediction accuracy. We used a 600 K Affymetrix platform with 1351 birds genotyped and phenotyped for three traits in broiler chickens; body weight, ultrasound measurement of breast muscle and hen house egg production. The predictive performance of GBLUP versus BGBLUP was evaluated in different scenarios consisting of including or excluding the TOP 20 markers from a standard genome-wide association study (GWAS) as fixed effects in the GBLUP model, and varying training sample sizes and allelic frequency bins. Predictive performance was assessed via five replications of a threefold cross-validation using the correlation between observed and predicted values, and prediction mean-squared error. GBLUP overfitted the training set data, and BGBLUP delivered a better predictive ability in testing sets. Treating the TOP 20 markers from the GWAS into the model as fixed effects improved prediction accuracy and added advantages to BGBLUP over GBLUP. The performance of GBLUP and BGBLUP at different allele frequency bins and training sample sizes was similar. In general, results of this study confirm that BGBLUP can be valuable for enhancing genome-enabled prediction of complex traits. PMID:25727456

  20. Genomic response to Wnt signalling is highly context-dependent - Evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets

    International Nuclear Information System (INIS)

    Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand. The anti-β-catenin immunoprecipitation of DNA-protein complexes from mouse NIH3T3 fibroblasts expressing a fusion protein of β-catenin and TCF7 resulted in the identification of 92 genes as putative TCF targets. GeneChip assays of gene expression performed on NIH3T3 cells and the rat pheochromocytoma cell line PC12 revealed 355 genes in NIH3T3 and 129 genes in the PC12 cells with marked changes in expression after Wnt3a stimulus. Only 2 Wnt-regulated genes were shared by both cell lines. Surprisingly, Disabled-2 was the only gene identified by the chromatin immunoprecipitation approach that displayed a marked change in expression in the GeneChip assay. Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling.

  1. Quetiapine: recent developments in preclinical research

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    Marco Orsetti

    2010-03-01

    Full Text Available Quetiapine (QTP is an atypical antipsychotic labelled for the treatment of patients with schizophrenia, bipolar mania and bipolar depression. Nevertheless, QTP has been tried across multiple diagnosis categories and seems to be used, among other atypical antipsychotics, in clinical practice for an expanding range of disorders such as major depression, substance abuse disorders, anxiety disorders, and borderline personality disorders. The present review focuses on papers which investigated the molecular mechanism(s of QTP antidepressant effect. In particular, preclinical studies performed by coupling the chronic mild stress, an animal model of human depression with Affymetrix microarray technology, revealed that chronic QTP administration prevented the stress-induced up- or down-regulation of 42 genes involved in the central nervous system development or having a crucial role for viability of neural cells, like regulation of signal transduction, inorganic ion transport, membrane organisation, and neurite morphogenesis. Among these, Ptgs2, Hes5, Plcb1, Senp2, Gad1, and Marcks are presumably the effectors of the QTP clinical efficacy.

  2. Transcriptome response analysis of Arabidopsis thaliana to leafminer (Liriomyza huidobrensis

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    Zhang Sufang

    2012-12-01

    Full Text Available Abstract Background Plants have evolved a complicated resistance system and exhibit a variety of defense patterns in response to different attackers. Previous studies have shown that responses of plants to chewing insects and phloem-feeding insects are significantly different. Less is known, however, regarding molecular responses to leafminer insects. To investigate plant transcriptome response to leafminers, we selected the leafminer Liriomyza huidobrensis, which has a special feeding pattern more similar to pathogen damage than that of chewing insects, as a model insect, and Arabidopsis thaliana as a response plant. Results We first investigated local and systemic responses of A. thaliana to leafminer feeding using an Affymetrix ATH1 genome array. Genes related to metabolic processes and stimulus responses were highly regulated. Most systemically-induced genes formed a subset of the local response genes. We then downloaded gene expression data from online databases and used hierarchical clustering to explore relationships among gene expression patterns in A. thaliana damaged by different attackers. Conclusions Our results demonstrate that plant response patterns are strongly coupled to damage patterns of attackers.

  3. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.

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    Anne Planche

    Full Text Available Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.

  4. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology. PMID:27052691

  5. Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

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    Skoog Lambert

    2006-06-01

    Full Text Available Abstract Background Postmenopausal hormone-replacement therapy (HRT increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results HRT use in patients with estrogen receptor (ER protein positive tumors (n = 72 was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.

  6. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

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    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

  7. Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress

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    Gupta, Aarti; Sarkar, Ananda K.; Senthil-Kumar, Muthappa

    2016-01-01

    With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN) demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed “tailored” responses under combined stress and the time of occurrence of each stress during their concurrence has shown differences in transcriptome profile. Our results from microarray and RT-qPCR revealed regulation of 20 novel genes uniquely during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions, time of occurrence of each stress in the interaction defines the plant responses and should thus be studied explicitly.

  8. Bronchial airway gene expression in smokers with lung or head and neck cancer

    International Nuclear Information System (INIS)

    Cigarette smoking is the major cause of cancers of the respiratory tract, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). In order to better understand carcinogenesis of the lung and upper airways, we have compared the gene expression profiles of tumor-distant, histologically normal bronchial biopsy specimens obtained from current smokers with NSCLC or HNC (SC, considered as a single group), as well as nonsmokers (NS) and smokers without cancer (SNC). RNA from a total of 97 biopsies was used for gene expression profiling (Affymetrix HG-U133 Plus 2.0 array). Differentially expressed genes were used to compare NS, SNC, and SC, and functional analysis was carried out using Ingenuity Pathway Analysis (IPA). Smoking-related cancer of the respiratory tract was found to affect the expression of genes encoding xenobiotic biotransformation proteins, as well as proteins associated with crucial inflammation/immunity pathways and other processes that protect the airway from the chemicals in cigarette smoke or contribute to carcinogenesis. Finally, we used the prediction analysis for microarray (PAM) method to identify gene signatures of cigarette smoking and cancer, and uncovered a 15-gene signature that distinguished between SNC and SC with an accuracy of 83%. Thus, gene profiling of histologically normal bronchial biopsy specimens provided insight into cigarette-induced carcinogenesis of the respiratory tract and gene signatures of cancer in smokers

  9. Aspergillus flavus infection induces transcriptional and physical changes in developing maize kernels

    Directory of Open Access Journals (Sweden)

    Andrea L Dolezal

    2014-07-01

    Full Text Available Maize kernels are susceptible to infection by the opportunistic pathogen Aspergillus flavus. Infection results in reduction of grain quality and contamination of kernels with the highly carcinogenic mycotoxin, aflatoxin. To understanding host response to infection by the fungus, transcription of approximately 9,000 maize genes were monitored during the host-pathogen interaction with a custom designed Affymetrix GeneChip® DNA array. More than 1,000 maize genes were found differentially expressed at a fold change of 2 or greater. This included the up regulation of defense related genes and signaling pathways. Transcriptional changes also were observed in primary metabolism genes. Starch biosynthetic genes were down regulated during infection, while genes encoding maize hydrolytic enzymes, presumably involved in the degradation of host reserves, were up regulated. These data indicate that infection of the maize kernel by A. flavus induced metabolic changes in the kernel, including the production of a defense response, as well as a disruption in kernel development.

  10. Analysis of purified glabra3-shapeshifter trichomes reveals a role for NOECK in regulating early trichome morphogenic events.

    Science.gov (United States)

    Gilding, Edward K; Marks, M David

    2010-10-01

    Transcriptome analysis using the Affymetrix ATH1 platform has been completed on purified trichomes from the gl3-sst mutant. These trichomes display immature features, such as glassy cell walls and blunted branches. The gl3-sst trichome transcriptome was greatly enriched for genes involved in lipid biosynthesis, including those mediating the synthesis of fatty acids and wax. In addition, gl3-sst trichomes displayed reduced expression of the R3 MYBs TRY and CPC, which normally function to limit trichome development. The expression of the MIXTA-like MYB gene NOK was elevated. Members of the MIXTA-like family promote conical cell outgrowth, and in some cases, trichome initiation in diverse plant species. In contrast, NOK limits trichome outgrowth in wild-type Arabidopsis plants. Similar to other MIXTA-like genes, NOK was required for the expansion of gl3-sst trichomes, as the gl3-sst nok double mutant trichomes were greatly reduced in size. Expression of NOK in nok mutants reduced branch formation, whereas in gl3-sst nok, NOK expression promoted trichome cell outgrowth, illustrating duel roles for NOK in both promoting and limiting trichome development. MIXTA-like genes from phylogenetically diverse plant species could substitute for NOK in both nok and gl3-sst nok backgrounds. These findings suggest that certain aspects of NOK and MIXTA-like gene function have been conserved. PMID:21070410

  11. Public Availability of a Genotyped Segregating Population May Foster Marker Assisted Breeding (MAB) and Quantitative Trait Loci (QTL) Discovery: An Example Using Strawberry.

    Science.gov (United States)

    Hancock, James F; Sooriyapathirana, Suneth S; Bassil, Nahla V; Stegmeir, Travis; Cai, Lichun; Finn, Chad E; Van de Weg, Eric; Weebadde, Cholani K

    2016-01-01

    Much of the cost associated with marker discovery for marker assisted breeding (MAB) can be eliminated if a diverse, segregating population is generated, genotyped, and made available to the global breeding community. Herein, we present an example of a hybrid, wild-derived family of the octoploid strawberry that can be used by other breeding programs to economically find and tag useful genes for MAB. A pseudo test cross population between two wild species of Fragaria virginiana and F. chiloensis (FVC 11) was generated and evaluated for a set of phenotypic traits. A total of 106 individuals in the FVC 11 were genotyped for 29,251 single nucleotide polymorphisms (SNPs) utilizing a commercially available, genome-wide scanning platform (Affymetrix Axiom IStraw90(TW)). The marker trait associations were deduced using TASSEL software. The FVC 11 population segregating for daughters per mother, inflorescence number, inflorescence height, crown production, flower number, fruit size, yield, internal color, soluble solids, fruit firmness, and plant vigor. Coefficients of variations ranged from 10% for fruit firmness to 68% for daughters per mother, indicating an underlying quantitative inheritance for each trait. A total of 2,474 SNPs were found to be polymorphic in FVC 11 and strong marker trait associations were observed for vigor, daughters per mother, yield and fruit weight. These data indicate that FVC 11 can be used as a reference population for quantitative trait loci detection and subsequent MAB across different breeding programs and geographical locations. PMID:27242825

  12. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  13. Brain stem global gene expression profiles in human spina bifida embryos

    Institute of Scientific and Technical Information of China (English)

    Hong Zhao; Xiang Li; Wan-I Lie; Quanren He; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2011-01-01

    Environmental and genetic factors influence the occurrence of neural tube defects, such as spina bifida.Specific disease expression patterns will help to elucidate the pathogenesis of disease.However, results obtained from animal models, which often exhibit organism specificity, do not fully explain the mechanisms of human spina bifida onset.In the present study, three embryos with a gestational age of approximately 17 weeks and a confirmed diagnosis of spina bifida, as well as 3 age-matched normal embryos, were obtained from abortions.Fetal brain stem tissues were dissected for RNA isolation, and microarray analyses were conducted to examine profiles of gene expression in brain stems of spina bifida and normal embryos using Affymetrix HG-U1 33A 2.0 GeneChip arrays.Of the 14 500 gene transcripts examined, a total of 182 genes exhibited at least 2.5-fold change in expression, including 140 upregulated and 42 downregulated genes.These genes were placed into 19 main functional categories according to the Gene Ontology Consortium database for biological functions.Of the 182 altered genes, approximately 50% were involved in cellular apoptosis, growth, adhesion, cell cycle, stress, DNA replication and repair, signal transduction, nervous system development, oxidoreduction, immune responses, and regulation of gene transcription.Gene expression in multiple biological pathways was altered in the brain stem of human spina bifida embryos.

  14. Identification of WSB1 gene as an important regulator in the development of zebrafish embryo during midblastula transition

    Institute of Scientific and Technical Information of China (English)

    Wenjian Lv; Yunbin Zhang; Zhili Wu; Lin Chu; S. S. Koide; Yuguang Chen; Yuanchang Yan; Yiping Li

    2008-01-01

    To uncover novel genes potentially involved in embryo development, especially at the midblastula transition (MBT) phase in the developing embryo of zebrafish, Affymetrix zebrafish GeneChip microarray analysis was carried out on the expression of 14,900 gene transcripts. The results of the analysis showed that 360 genes were clearly up-regulated and 119 genes were markedly down-regulated. Many of these genes were involved in transcription factor activity, nucleic acid binding, and cell growth. The present study showed that significant changes in transcript abundance occurred during the MBT phase. The expression of eight of these 479 genes was identified by reverse transcription-polymerase chain reaction analysis, confirming the microarray results. The WSB1 gene, found to be down-regulated by the microarray and reverse transcription-polymerase chain reaction analyses, was selected for further study. Sequence analysis of the WSB1 gene showed that it encodes a protein with 75% identity to the corresponding active human orthologs. In addition, WSB1 gene expression was detected at a higher level at 2 h post fertilization and at a lower level at 4 h post fertilization, consistent with the chip results. Overexpression of the WSB1 gene can result in the formation of abnormalities in embryos, as determined by fluorescence-activated cell sorting. The present study showed unequivo- cally that the occurrence of WSB1 expression is an impor-tant event during the MBT phase in the development of zebrafish embryos.

  15. A novel syndrome of paediatric cataract, dysmorphism, ectodermal features, and developmental delay in Australian Aboriginal family maps to 1p35.3-p36.32

    Directory of Open Access Journals (Sweden)

    Gecz Jozef

    2010-11-01

    Full Text Available Abstract Background A novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent. Large scale chromosomal re-arrangements had previously been ruled out. We have conducted a genome-wide scan to map the linkage region in this family. Methods Genome-wide linkage analysis using Single Nucleotide Polymorphism (SNP markers on the Affymetrix 10K SNP array was conducted and analysed using MERLIN. Three positional candidate genes (ZBTB17, EPHA2 and EPHB2 were sequenced to screen for segregating mutations. Results Under a fully penetrant, dominant model, the locus for this unique phenotype was mapped to chromosome 1p35.3-p36.32 with a maximum LOD score of 2.41. The critical region spans 48.7 cM between markers rs966321 and rs1441834 and encompasses 527 transcripts from 364 annotated genes. No coding mutations were identified in three positional candidate genes EPHA2, EPHB2 or ZBTB17. The region overlaps with a previously reported region for Volkmann cataract and the phenotype has similarity to that reported for 1p36 monosomy. Conclusions The gene for this syndrome is located in a 25.6 Mb region on 1p35.3-p36.32. The known cataract gene in this region (EPHA2 does not harbour mutations in this family, suggesting that at least one additional gene for cataract is present in this region.

  16. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    Directory of Open Access Journals (Sweden)

    Gisele Negro Lima

    2015-02-01

    Full Text Available OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.

  17. Gene expression changes in GABA(A receptors and cognition following chronic ketamine administration in mice.

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    Sijie Tan

    Full Text Available Ketamine is a well-known anesthetic agent and a drug of abuse. Despite its widespread use and abuse, little is known about its long-term effects on the central nervous system. The present study was designed to evaluate the effect of long-term (1- and 3-month ketamine administration on learning and memory and associated gene expression levels in the brain. The Morris water maze was used to assess spatial memory and gene expression changes were assayed using Affymetrix Genechips; a focus on the expression of GABA(A receptors that mediate a tonic inhibition in the brain, was confirmed by quantitative real-time PCR and western blot. Compared with saline controls, there was a decline in learning and memory performance in the ketamine-treated mice. Genechip results showed that 110 genes were up-regulated and 136 genes were down-regulated. An ontology analysis revealed the most significant effects of ketamine were on GABA(A receptors. In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5 of the GABA(A receptors in the prefrontal cortex. In conclusion, chronic exposure to ketamine impairs working memory in mice, which may be explained at least partly by up-regulation of Gabra5 subunits in the prefrontal cortex.

  18. Genomic response to Wnt signalling is highly context-dependent - Evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets

    Energy Technology Data Exchange (ETDEWEB)

    Railo, Antti [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Pajunen, Antti [Department of Biochemistry, University of Oulu (Finland); Itaeranta, Petri; Naillat, Florence; Vuoristo, Jussi; Kilpelaeinen, Pekka [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Vainio, Seppo, E-mail: Seppo.Vainio@oulu.fi [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)

    2009-10-01

    Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand. The anti-{beta}-catenin immunoprecipitation of DNA-protein complexes from mouse NIH3T3 fibroblasts expressing a fusion protein of {beta}-catenin and TCF7 resulted in the identification of 92 genes as putative TCF targets. GeneChip assays of gene expression performed on NIH3T3 cells and the rat pheochromocytoma cell line PC12 revealed 355 genes in NIH3T3 and 129 genes in the PC12 cells with marked changes in expression after Wnt3a stimulus. Only 2 Wnt-regulated genes were shared by both cell lines. Surprisingly, Disabled-2 was the only gene identified by the chromatin immunoprecipitation approach that displayed a marked change in expression in the GeneChip assay. Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling.

  19. Investigating the global genomic diversity of Escherichia coli using a multi-genome DNA microarray platform with novel gene prediction strategies

    Directory of Open Access Journals (Sweden)

    LeClerc Joseph E

    2011-07-01

    Full Text Available Abstract Background The gene content of a diverse group of 183 unique Escherichia coli and Shigella isolates was determined using the Affymetrix GeneChip® E. coli Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping tool. The probe set design utilized by this array provided the opportunity to determine the gene content of each strain very accurately and reliably. This array constitutes 10,112 independent genes representing four individual E. coli genomes, therefore providing the ability to survey genes of several different pathogen types. The entire ECOR collection, 80 EHEC-like isolates, and a diverse set of isolates from our FDA strain repository were included in our analysis. Results From this study we were able to define sets of genes that correspond to, and therefore define, the EHEC pathogen type. Furthermore, our sampling of 63 unique strains of O157:H7 showed the ability of this array to discriminate between closely related strains. We found that individual strains of O157:H7 differed, on average, by 197 probe sets. Finally, we describe an analysis method that utilizes the power of the probe sets to determine accurately the presence/absence of each gene represented on this array. Conclusions These elements provide insights into understanding the microbial diversity that exists within extant E. coli populations. Moreover, these data demonstrate that this novel microarray-based analysis is a powerful tool in the field of molecular epidemiology and the newly emerging field of microbial forensics.

  20. Integrating data from heterogeneous DNA microarray platforms.

    Science.gov (United States)

    Valente, Eduardo; Rocha, Miguel

    2015-01-01

    DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re-annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID:26673932

  1. PTTG1 Over-expression in Adrenocortical Cancer is Associated with Poor Survival and Represents a Potential Therapeutic Target

    Science.gov (United States)

    Demeure, Michael J.; Coan, Kathryn E.; Grant, Clive S.; Komorowski, Richard A.; Stephan, Elizabeth; Sinari, Shripad; Mount, David; Bussey, Kimberly J.

    2014-01-01

    Background Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data for prognostic biomarkers and therapeutic targets. Methods 44 ACC and 4 normal adrenals were profiled on Affymetrix U133 Plus 2 expression microarrays. Pathway and transcriptional enrichment analysis was performed. Protein levels were determined by western blot. Drug efficacy was assessed against ACC cell lines. Previously published expression datasets were analyzed for validation. Results Pathway enrichment analysis identified marked dysregulation of cyclin-dependent kinases and mitosis. Over-expression of PTTG1, which encodes securin, a negative regulator of p53, was identified as a marker of poor survival. Median survival for patients with tumors expressing high PTTG1 levels (log2 ratio of PTTG1 to average beta-actin <-3.04 ) was 1.8 years compared to 9.0 years if tumors expressed lower levels of PTTG1 (P<0.0001). Analysis of a previously published data set confirmed the association of high PTTG1 expression with a poor prognosis. Treatment of two ACC cell lines with vorinostat decreased securin levels and inhibited cell growth (IC50s of 1.69 uM and 0.891 uM, for SW-13 and H295R, respectively). Conclusion Over-expression of PTTG1 is correlated with poor survival in ACC. PTTG1/securin is a prognostic biomarker and warrants investigation as a therapeutic target. PMID:24238056

  2. Disruption of O-GlcNAc cycling by deletion of O-GlcNAcase (Oga/Mgea5 changed gene expression pattern in mouse embryonic fibroblast (MEF cells

    Directory of Open Access Journals (Sweden)

    Chithra Keembiyehetty

    2015-09-01

    Full Text Available Adding a single O-GlcNAc moiety to a Ser/Thr molecule of a protein by O-GlcNAc transferase and transiently removing it by O-GlcNAcase is referred to as O-GlcNAc cycling (or O-GlcNAcylation. This O-GlcNAc modification is sensitive to nutrient availability and also shows cross talk with phosphorylation signaling, affecting downstream targets. A mouse model system was developed and evaluated to show genome wide transcriptional changes associated with disruption of O-GlcNAc cycling. Mouse embryonic fibroblast cells derived from O-GlcNAcase (Oga knock out (KO, heterozygous (Het and wild type (WT embryos were used for an Affymetrix based microarray. Results are deposited in GEO dataset GSE52721. Data reveals that Oga KO MEFs had 2534 transcripts differentially expressed at 1.5 fold level while Oga heterozygous MEFs had 959 transcripts changed compared to WT MEFs. There were 1835 transcripts differentially expressed at 1.5 fold Het versus WT comparison group. Gene ontology analysis indicated differentially expressed genes enriched in metabolic, growth, and cell proliferation categories.

  3. Gene expression profiling of tumours derived from rasV12/E1A-transformed mouse embryonic fibroblasts to identify genes required for tumour development

    Directory of Open Access Journals (Sweden)

    Dagorn Jean

    2005-01-01

    Full Text Available Abstract Background In cancer, cellular transformation is followed by tumour development. Knowledge on the mechanisms of transformation, involving activation of proto-oncogenes and inactivation of tumour-suppressor genes has considerably improved whereas tumour development remains poorly understood. An interesting way of gaining information on tumour progression mechanisms would be to identify genes whose expression is altered during tumour formation. We used the Affymetrix-based DNA microarray technology to analyze gene expression profiles of tumours derived from rasV12/E1A-transformed mouse embryo fibroblasts in order to identify the genes that could be involved in tumour development. Results Among the 12,000 genes analyzed in this study, only 489 showed altered expression during tumour development, 213 being up-regulated and 276 down-regulated. The genes differentially expressed are involved in a variety of cellular functions, including control of transcription, regulation of mRNA maturation and processing, regulation of protein translation, activation of interferon-induced genes, intracellular signalling, apoptosis, cell growth, angiogenesis, cytoskeleton, cell-to-cell interaction, extracellular matrix formation, metabolism and production of secretory factors. Conclusions Some of the genes identified in this work, whose expression is altered upon rasV12/E1A transformation of MEFs, could be new cancer therapeutic targets.

  4. The ROS Wheel: Refining ROS Transcriptional Footprints1[OPEN

    Science.gov (United States)

    Noctor, Graham

    2016-01-01

    In the last decade, microarray studies have delivered extensive inventories of transcriptome-wide changes in messenger RNA levels provoked by various types of oxidative stress in Arabidopsis (Arabidopsis thaliana). Previous cross-study comparisons indicated how different types of reactive oxygen species (ROS) and their subcellular accumulation sites are able to reshape the transcriptome in specific manners. However, these analyses often employed simplistic statistical frameworks that are not compatible with large-scale analyses. Here, we reanalyzed a total of 79 Affymetrix ATH1 microarray studies of redox homeostasis perturbation experiments. To create hierarchy in such a high number of transcriptomic data sets, all transcriptional profiles were clustered on the overlap extent of their differentially expressed transcripts. Subsequently, meta-analysis determined a single magnitude of differential expression across studies and identified common transcriptional footprints per cluster. The resulting transcriptional footprints revealed the regulation of various metabolic pathways and gene families. The RESPIRATORY BURST OXIDASE HOMOLOG F-mediated respiratory burst had a major impact and was a converging point among several studies. Conversely, the timing of the oxidative stress response was a determining factor in shaping different transcriptome footprints. Our study emphasizes the need to interpret transcriptomic data sets in a systematic context, where initial, specific stress triggers can converge to common, aspecific transcriptional changes. We believe that these refined transcriptional footprints provide a valuable resource for assessing the involvement of ROS in biological processes in plants. PMID:27246095

  5. Global transcriptional analysis reveals unique and shared responses in Arabidopsis thaliana exposed to combined drought and pathogen stress

    Directory of Open Access Journals (Sweden)

    Aarti eGupta

    2016-05-01

    Full Text Available With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000 infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed ‘tailored’ responses under combined stress and the time of occurrence of each stress during their concurrence has showed differences in transcriptome profile. Our results from microarray and RT-qPCR revealed unique regulation of 20 novel genes exclusively during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions each combination of stressor and their timing defines the plant responses and should thus be studied explicitly.

  6. Mapping transcriptome profiles of in vitro iPSC-derived cardiac differentiation to in utero heart development

    Directory of Open Access Journals (Sweden)

    Xing Li

    2016-03-01

    Full Text Available The dataset includes microarray data (Affymetrix Mouse Genome 430 2.0 Array from WT and Nos3−/− mouse embryonic heart ventricular tissues at 14.5 days post coitum (E14.5, induced pluripotent stem cells (iPSCs derived from WT and Nos3−/− mouse tail tip fibroblasts, iPSC-differentiated cardiomyocytes at Day 11, and mouse embryonic stem cells (mESCs and differentiated cardiomyocytes as positive controls for mouse iPSC differentiation. Both in utero (using embryonic heart tissues and in vitro (using iPSCs and differentiated cells microarray datasets were deposited to the NCBI Gene Expression Omnibus (GEO database. The deposited data in GEO include raw microarray data, metadata for sample source information, experimental design, sample and data processing, and gene expression matrix. The data are available under GEO Access Number GSE69317 (GSE69315 for tissue sample microarray data, GSE69316 for iPSCs microarray data, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE69317.

  7. Genome-wide association study of periodontal pathogen colonization.

    Science.gov (United States)

    Divaris, K; Monda, K L; North, K E; Olshan, A F; Lange, E M; Moss, K; Barros, S P; Beck, J D; Offenbacher, S

    2012-07-01

    Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease. PMID:22699663

  8. Genome-Wide Association Study of a Varroa-Specific Defense Behavior in Honeybees (Apis mellifera).

    Science.gov (United States)

    Spötter, Andreas; Gupta, Pooja; Mayer, Manfred; Reinsch, Norbert; Bienefeld, Kaspar

    2016-05-01

    Honey bees are exposed to many damaging pathogens and parasites. The most devastating is Varroa destructor, which mainly affects the brood. A promising approach for preventing its spread is to breed Varroa-resistant honey bees. One trait that has been shown to provide significant resistance against the Varroa mite is hygienic behavior, which is a behavioral response of honeybee workers to brood diseases in general. Here, we report the use of an Affymetrix 44K SNP array to analyze SNPs associated with detection and uncapping of Varroa-parasitized brood by individual worker bees (Apis mellifera). For this study, 22 000 individually labeled bees were video-monitored and a sample of 122 cases and 122 controls was collected and analyzed to determine the dependence/independence of SNP genotypes from hygienic and nonhygienic behavior on a genome-wide scale. After false-discovery rate correction of the P values, 6 SNP markers had highly significant associations with the trait investigated (α < 0.01). Inspection of the genomic regions around these SNPs led to the discovery of putative candidate genes. PMID:26774061

  9. Dietary inulin supplementation modifies significantly the liver transcriptomic profile of broiler chickens.

    Science.gov (United States)

    Sevane, Natalia; Bialade, Federica; Velasco, Susana; Rebolé, Almudena; Rodríguez, Maria Luisa; Ortiz, Luís T; Cañón, Javier; Dunner, Susana

    2014-01-01

    Inclusion of prebiotics in the diet is known to be advantageous, with positive influences both on health and growth. The current study investigated the differences in the hepatic transcriptome profiles between chickens supplemented with inulin (a storage carbohydrate found in many plants) and controls. Liver is a major metabolic organ and has been previously reported to be involved in the modification of the lipid metabolism in chickens fed with inulin. A nutrigenomic approach through the analysis of liver RNA hybridized to the Affymetrix GeneChip Chicken Genome Array identified 148 differentially expressed genes among both groups: 104 up-regulated (≥ 1.4-fold) and 44 down-regulated (≤ 0.6-fold). Quantitative real-time PCR analysis validated the microarray expression results for five out of seven genes tested. The functional annotation analyses revealed a number of genes, processes and pathways with putative involvement in chicken growth and performance, while reinforcing the immune status of animals, and fostering the production of long chain fatty acids in broilers supplemented with 5 g of inulin kg(-1) diet. As far as we are aware, this is the first report of a microarray based gene expression study on the effect of dietary inulin supplementation, supporting further research on the use of this prebiotic on chicken diets as a useful alternative to antibiotics for improving performance and general immunity in poultry farming, along with a healthier meat lipid profile. PMID:24915441

  10. TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

    International Nuclear Information System (INIS)

    TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear. We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays. Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors. The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy

  11. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide

    Science.gov (United States)

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P.; Telander, David G.; Hjelmeland, Leonard M.; Morse, Lawrence S.

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.

  12. Identification and validation of quantitative trait loci (QTL) for canine hip dysplasia (CHD) in German Shepherd Dogs.

    Science.gov (United States)

    Fels, Lena; Distl, Ottmar

    2014-01-01

    Canine hip dysplasia (CHD) is the most common hereditary skeletal disorder in dogs. To identify common alleles associated with CHD, we genotyped 96 German Shepherd Dogs affected by mild, moderate and severe CHD and 96 breed, sex, age and birth year matched controls using the Affymetrix canine high density SNP chip. A mixed linear model analysis identified five SNPs associated with CHD scores on dog chromosomes (CFA) 19, 24, 26 and 34. These five SNPs were validated in a by sex, age, birth year and coancestry stratified sample of 843 German Shepherd Dogs including 277 unaffected dogs and 566 CHD-affected dogs. Mean coancestry coefficients among and within cases and controls were Dogs employed for validation. Genome-wide significance in the validation data set could be shown for each one CHD-associated SNP on CFA24, 26 and 34. These SNPs are located within or in close proximity of genes involved in bone formation and related through a joint network. The present study validated positional candidate genes within two previously known quantitative trait loci (QTL) and a novel QTL for CHD in German Shepherd Dogs. PMID:24802516

  13. Whole transcriptome data analysis of mouse embryonic hematopoietic stem and progenitor cells that lack Geminin expression.

    Science.gov (United States)

    L Patmanidi, Alexandra; Kanellakis, Nikolaos I; Karamitros, Dimitris; Papadimitriou, Christos; Lygerou, Zoi; Taraviras, Stavros

    2016-06-01

    We performed cDNA microarrays (Affymetrix Mouse Gene 1.0 ST Chip) to analyze the transcriptome of hematopoietic stem and progenitor cells (HSPCs) from E15.5dpc wild type and Geminin (Gmnn) knockout embryos. Lineage negative cells from embryonic livers were isolated using fluorescence activated cell sorting. RNA samples were used to examine the transcriptional programs regulated by Geminin during embryonic hematopoiesis. The data sets were analyzed using the GeneSpring v12.5 platform (Agilent). The list of differentially expressed genes was filtered in meta-analyses to investigate the molecular basis of the phenotype observed in the knockout embryos, which exhibited defective hematopoiesis and death. The data from this study are related to the research article "Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors" (Karamitros et al., 2015) [1]. The microarray dataset has been deposited at the Gene Expression Omnibus (GEO) under accession GEO: GSE53056. PMID:27077091

  14. A Pooled Genome-Wide Association Study of Asperger Syndrome.

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    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  15. Chromosomal microarrays testing in children with developmental disabilities and congenital anomalies

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    Guillermo Lay-Son

    2015-04-01

    Full Text Available OBJECTIVES: Clinical use of microarray-based techniques for the analysis of many developmental disorders has emerged during the last decade. Thus, chromosomal microarray has been positioned as a first-tier test. This study reports the first experience in a Chilean cohort. METHODS: Chilean patients with developmental disabilities and congenital anomalies were studied with a high-density microarray (CytoScan(tm HD Array, Affymetrix, Inc., Santa Clara, CA, USA. Patients had previous cytogenetic studies with either a normal result or a poorly characterized anomaly. RESULTS: This study tested 40 patients selected by two or more criteria, including: major congenital anomalies, facial dysmorphism, developmental delay, and intellectual disability. Copy number variants (CNVs were found in 72.5% of patients, while a pathogenic CNV was found in 25% of patients and a CNV of uncertain clinical significance was found in 2.5% of patients. CONCLUSION: Chromosomal microarray analysis is a useful and powerful tool for diagnosis of developmental diseases, by allowing accurate diagnosis, improving the diagnosis rate, and discovering new etiologies. The higher cost is a limitation for widespread use in this setting.

  16. Molecular mechanism of immune response induced by foreign plasmid DNA after oral administration in mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study immune response induced by foreign plasmid DNA after oral administration in mice.METHODS: Mice were orally administered with 200 μg of plasmid pcDNA3 once and spleen was isolated 4 h and 18 h after administration. Total RNA was extracted from spleen and gene expression profile of BALB/c mice spleen was analyzed by using Affymetrix oligonucleotide GeneChip. Functional cluster analysis was conducted by GenMAPP software.RESULTS: At 4 h and 18 h after oral plasmid pcDNA3 administration, a number of immune-related genes,including cytokine and cytokine receptors, chemokines and chemokine receptor, complement molecule,proteasome, histocompatibility molecule, lymphocyte antigen complex and apoptotic genes, were up-regulated. Moreover, MAPPFinder results also showed that numerous immune response processes were up-regulated. In contrast, the immunoglobulin genes were down-regulated.CONCLUSION: Foreign plasmid DNA can modulate the genes expression related to immune system via the gastrointestinal tract, and further analysis of the related immune process may help understand the molecular mechanisms of immune response induced by foreign plasmid via the gastrointestinal tract.

  17. High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability.

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    Xiaohong Gong

    Full Text Available Intellectual disability (ID is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%, while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.

  18. Nickel-induced down-regulation of serpin by hypoxic signaling

    International Nuclear Information System (INIS)

    Nickel (Ni) carcinogenesis is thought to involve gene chip silencing by epigenetic mechanisms. Serpina3g, a member of the mouse serpin family, was among the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells based on the Affymetrix gene chip. Serpina3g down-regulation was controlled by a hypoxia inducible factor (HIF) mechanism. The exposure of cells to cobalt (Co), hypoxia, the iron chelator deferoxamine, and the proline hydroxylase inhibitor dimethyloxalylglycine (DMOG) also down-regulated serpina3g transcription to similar extents as soluble Ni exposure. These results support the mounting experimental evidence that water-soluble Ni compounds have a predominant effect on hypoxia signaling because of their ability to interfere with Fe homeostasis in the cell. Trichostatin A (TSA) and 5-azacytidine (5-AzaC) reactivated the Ni-silenced serpina3g gene, indicating that its silencing by Ni involved either a direct or indirect epigenetic mechanism. Analysis of the chromatin state of the serpina3g promoter by the ChIP assay revealed that exposure of mouse fibroblast cells to Ni resulted in the methylation of H3 lysine 9 within its promoter, as well as a decrease in the phosphorylation of serine 10 of H3 and a marked decrease in the acetylation of H3 and H4. Serpina3g gene expression returned to basal levels following Ni removal, suggesting that the observed silencing was a dynamic and reversible process

  19. Exploring Prostate Cancer Genome Reveals Simultaneous Losses of PTEN, FAS and PAPSS2 in Patients with PSA Recurrence after Radical Prostatectomy

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    Chinyere Ibeawuchi

    2015-02-01

    Full Text Available The multifocal nature of prostate cancer (PCa creates a challenge to patients’ outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients’ clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0–9.7 (mean 5.4 years, copy number variation (CNV data was evaluated for association with patients’ PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2–10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05. The implication of PTEN and FAS loss (10q23.31 support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2–10q23.31 may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy.

  20. Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells

    International Nuclear Information System (INIS)

    Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer. The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data. Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents. Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer